WO2009007726A2 - Abnormal blood conditions - Google Patents

Abstract

Methods for diagnosing whether a subject has, or is at risk of, an abnormal blood condition are described. The methods comprises determining the genotype of the subject at a single nucleotide polymorphism (SNP) position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response. Probes and kits for use in such methods, and methods of prophylaxis or treatment of abnormal blood conditions are also described.

Description

Abnormal Blood Conditions

This invention relates to the diagnosis of abnormal blood conditions, in particular to diagnosis of an increased risk of thrombosis, especially atherothrombosis (AT), or bleeding. The invention also relates to probes and kits for use in such methods, and methods of prophylaxis or treatment of abnormal blood conditions.

AT is the main cause of premature death in Western Society. Myocardial infarction, stroke and peripheral artery thrombosis are three clinical conditions in which activation of platelets is critical to the clinical event of formation of an occlusive thrombus. Collagen is the main extracellular matrix protein which is released upon atherosclerotic plaque rupture and is the prime activator of platelets under this pathological condition ^!'3. Adenosine-di-phosphate (ADP) is contained in platelet granules which are released upon stimulation of platelets by physiological agonists like collagen. ADP release further amplifies platelet activation. The importance of GPVI, the platelet collagen signalling receptor and P2RY1 and P2RY12, the ADP signalling receptors has been convincingly defined in humans because lack of the receptor leads to a bleeding phenotype ^4>s.

We have recently described the extent of interindividual variation in the response of human platelets to the agonists adenosine-di-phosphate (ADP) and cross-linked collagen-related peptide (CRP) ⁶. Signalling of platelets by ADP is via the P2RY1 and P2RY12 G protein coupled receptors (GPCRs) and cross-linked CRP (CRP-XL) signals via the glycoprotein (GP)VI/Fc receptor γ chain. In this platelet function study (PFS) in 506 healthy individuals flow cytometry was used to measure fibrinogen binding and P-selectin expression in response to a single, intermediate dose of ADP or CRP. Pathway specificity was ensured by blocking the main subsidiary signalling pathways. We observed the existence of substantial variation between individuals and between agonists in the level of cellular response.

Whilst exogenous factors such as age, hypertension, diabetes mellitus, hypercholesterolemia and cigarette smoking have an effect, it is clear that the platelet functional response is substantially genetically controlled. Studies in siblings ⁷ and twins ⁸ suggest the level of heritability is as high as 50%. Polymorphisms in platelet membrane receptors have been linked to variation response, however the effect is often relatively modest — usually of the order of <5% — and not always reproducible in subsequent studies. This is likely to be because complex functional traits are polygenic, with multiple alleles contributing incrementally to phenotype. Transcriptome studies from our laboratory and others have shown that an estimated 9,000 genes are transcribed in the megakaryocyte, of which ~ 5,000 can be detected in platelets^9"12. To date, efforts to study the relationship between sequence variation and platelet function ^13'15 have been limited by a biased selection of candidate genes based on a priori knowledge, absence of high resolution information on sequence variation resulting in inadequate selection of tagSNPs ¹⁶, often by small cohort sizes, and, importantly, by lack of critical evaluation and standardisation of methods to analyse platelet function.

We have applied a post-genome platform to study the association between sequence variation and the platelet cellular response to ADP and CRP. A genotyping study of 108 candidate genes in the 506 samples of the PFS cohort was carried out. By use of this innovative platform, hitherto not applied in platelet biology studies, we have found that sequence variation in 30 loci is associated with modification of platelet function.

According to the invention there is provided a method of diagnosing whether a subject has, or is at risk of, an abnormal blood condition, which comprises determining the genotype of the subject at a single nucleotide polymorphism (SNP) position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response.

Preferably the method is an in vitro method, suitably carried out on a biological sample obtained from the patient (for example a sample comprising leucocytes or another tissue sample or fluid which contains nucleated cells, e.g. sputum).

Reference to an allele of the SNP being associated with enhanced platelet response means that the presence of the allele is positively correlated with enhanced platelet response. An enhanced platelet response means that the platelet response is enhanced compared to an average response of a population of normal individuals.

Platelet response may be measured by any suitable method, for example mobilization of intracellular calcium, platelet aggregometry, or flow cytometric measurement of fibrinogen binding and/or P-selectin expression, in response to adenosine 5'- diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Such methods are described, for example, by Jones et al, 2007 (Journal of Thrombosis and Haemostasis, 5: 1756-1765).

A suitable size population of normal individuals may be, for example, 500 or more individuals, preferably Caucasoid individuals. An individual is regarded to be normal if they exhibit a platelet response within a range determined for healthy subjects as described by Jones et al., 2007 (Journal of Thrombosis and Haemostasis, 5: 1756-

1765). In particular, platelet response is preferably determined by flow cytometric measurement of the percentage of platelets positive for fibrinogen binding and/or P- selectin expression in response to a single dose of ADP (10^'7M) or cross-linked CRP

(CRP-XL) (0.1 microg ml/¹) as described by Jones et al. By such methods, a platelet response is considered to be within the range for a healthy subject if: fibrinogen binding to CRP-XL stimulated platelets is within the range 3.1% to 84.4% positive; fibrinogen binding to ADP stimulated platelets is within the range 3.5% to 78.8% positive;

CRP-XL induced P-selectin expression is within the range 6.2% to 90.3% positive; or

ADP induced P-selectin expression is within the range 2.8% to 54.1% positive.

Methods of the invention may be used to diagnose an abnormal blood condition associated with an increased risk of thrombosis (preferably atherothrombosis).

In other embodiments, methods of the invention may be used to diagnose an abnormal blood condition associated with an increased risk of bleeding. This may be achieved by determining whether the subject has an anti-thetical allele to the allele associated with enhanced platelet response at the SNP position. Enhanced platelet response includes enhanced platelet response to a platelet agonist, such as adenosine-di-phosphate (ADP), collagen, a synthetic collagen mimetic (such as collagen-related peptide (CRP)), thrombin, a thrombin mimetic, thromboxane, or epinephrine.

The gene associated with platelet response may be specifically associated with adenosine-di-phosphate (ADP)-stimulated platelet activation, collagen-related peptide (CRP)-stimulated (or collagen-stimulated) platelet activation, or ADP- and CRP- stimulated (or collagen-stimulated) platelet activation.

ADP- or CRP-stimulated platelet activation may be measured by P-selectin expression and/or fibrinogen binding in response to ADP or CRP, as appropriate.

The gene specifically associated with ADP-stimulated platelet activation (i.e. associated with ADP-stimulated platelet activation, but not with CRP-stimulated platelet activation) may be any of the following genes: RAFl, JAK2, P2RY12, GNAZ, VAV3, PFKL, ITGA2, ITPRl, MAP2K2, MAPK14, MADD, MAP2K1, PTGS2, or MAP2K5.

Preferably the SNP position is selected from any of the following: position rs3729931 of RAFl; position rslO429491 of JAK2; position rsl472122 of P2RY12; a position corresponding to position NT_011520.10_2802586 of GNAZ SEQ ID NO: 1; a position corresponding to position NT_019273.17_4225076 of VAV3 SEQ ID NO: 2; position rs2838551 of PFKL; position rs41305896 of ITGA2; position rs41304179 of ITPRl; position rs350916 of MAP2K2; position rs851007 of MAPK14; position rs41304345 of MADD; position rs 11637556 of MAP2K1; position rs5277 of PTGS2; or position rsl 1631474 of MAP2K5.

The gene specifically associated with CRP-stimulated platelet activation (i.e. associated with CRP-stimulated platelet activation, but not with ADP-stimulated platelet activation) may be any of the . following genes: GP6, GNA 12, FCERlG, CD36, AKT2, MAP2K4, LAT, VAVl, TBXASl, INSR, or CDC42. Preferably the SNP position is selected from any of the following: position rsl613662 of GP6; position 41304915 of GNA12; position rs3557 of FCERlG; position rslO49654 of CD36; position rs41275750 of AKT2; position rs41307923 of MAP2K4; position rsl802141 of LAT, position rsl 86295 of VAVl; position rs2072179 of TBXASl; position rs6510959 of INSR; or position rs7544500 of CDC42.

The gene associated with both ADP- and CRP-stimulated platelet activation may be any of the following genes: PEARl, C0MMD7, GAS6, PLA2G2A or PLCBl.

Preferably the SNP position is selected from any of the following: position rs3737224 of PEARl; position rs6141803 of COMMD7; position rs41307142 of GAS6; position rs2307246 of PLA2G2A; or position rsl 6994453 of PLCBl.

Preferably the genotype of at least 2 (or at least 3, 4, 5, 6, 7, 8, 9, 10) SNP positions is determined.

In a preferred embodiment, the genotype may be determined at a SNP position in a gene specifically associated with ADP-stimulated platelet activation, and in a gene specifically associated with CRP-stimulated platelet activation.

In a preferred embodiment, the genotype may be determined at a SNP position in a gene specifically associated with ADP-stimulated platelet activation, and in a gene specifically associated with ADP- and CRP-stimulated platelet activation.

In a preferred embodiment, the genotype may be determined at a SNP position in a gene specifically associated with CRP-stimulated platelet activation, and in a gene specifically associated with ADP- and CRP-stimulated platelet activation.

Preferably it is determined whether the subject is homozygous or heterozygous for an allele at the SNP position.

Preferably the subject is a human subject, preferably a Caucasian. Methods for determining the genotype at a SNP position are well known to those of ordinary skill in the art. Suitable methods include real-time PCR, fluorimetric analysis, restriction enzyme analysis, restriction fragment length polymorphism (RFLP), single strand conformation polymorphism (SSCP), or use of a probe (preferably a labelled probe) which hybridises specifically to a region of nucleic acid acid which includes the SNP, and sequencing of nucleic acid.

Genomic DNA, RNA (for example platelet mRNA or total RNA), cDNA, or nucleic acid amplified from genomic DNA, RNA, or cDNA may be used for determining the genotype of the subject at the SNP position.

There is also provided according to the invention an oligonucleotide probe capable of specifically detecting an allele at a SNP position in a gene associated with platelet response, wherein the allele is associated with enhanced platelet response, or wherein the allele is anti-thetical to an allele that is associated with enhanced platelet response.

A probe of the invention preferably hybridises specifically to a region of nucleic acid of the gene that includes the allele. The probe preferably hybridises under stringent conditions to the region of nucleic acid. Stringent conditions are defined herein as O.lx SSC, 0.1% SDS at 65⁰C. Preferably under such conditions the probe does not hybridise to nucleic acid of the gene that includes a different allele at the SNP position. Such probes can be used to distinguish nucleic acid of the gene that includes the allele from nucleic acid of the gene that does not include the allele.

The oligonucleotide is preferably at least 20 (more preferably at least 30) nucleotides long. The oligonucleotide is preferably less than 100 nucleotides long (more preferably less than 50 nucleotides long). The sequence of the oligonucleotide is preferably at least 90%, more preferably at least 95%, more preferably 100% identical to the complement of the nucleic acid sequence of the gene in the region that includes the allele.

Preferably the gene associated with platelet response is specifically associated with adenosine-di-phosphate (ADP)-stimulated platelet activation, collagen-related peptide (CRP)-stimulated platelet activation, or with ADP- and CRP-stimulated platelet activation.

There is further provided according to the invention a kit for diagnosing whether a subject has, or is at risk of, an abnormal blood condition, which comprises means for determining the genotype of the subject at a SNP position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response, or is anti-thetical to an allele that is associated with enhanced platelet response.

Preferably the determining means comprises a probe of the invention.

A kit of the invention may include all the reagents necessary for determining the genotype of the subject at the SNP position.

In addition to the determining means, a kit of the invention may comprise one or more of the following: i) instructions for using the detecting means for diagnosis, prognosis, or therapeutic monitoring; ii) a label for detecting the detecting means; iii) a solid phase to which the detecting means is immobilised; iv) a label or insert indicating regulatory approval for diagnostic, prognostic or therapeutic use as appropriate; v) reagents for isolating or obtaining genomic DNA, mRNA or cDNA from a biological sample obtained from the subject; vi) oligonucleotide primers for amplification of nucleic acid that includes the SNP position.

There is also provided according to the invention use of a probe of the invention, or a kit of the invention, for the diagnosis of an abnormal blood condition.

The abnormal blood condition may be associated with an increased risk of thrombosis, or with an increased risk of bleeding. There is also provided according to the invention use of a method of the invention, a probe of the invention, or a kit of the invention, to identify subjects for participation in a clinical trial to assess a drug candidate for treatment of an abnormal blood condition.

The drug candidate may be a blood thinning drug candidate, Le. an anti-thrombotic, a thrombolytic, an anti-platelet drug, or other drugs which reduces the risk of thrombus formation.

There is further provided according to the invention a method of preventing, treating, or ameliorating an abnormal blood condition, which comprises determining the genotype of the subject at a single nucleotide polymorphism (SNP) position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response, and administering an appropriate prophylactic or treatment, or adjusting an ongoing prophylactic or treatment course, based on the result of the determination.

The prophylactic or treatment may be a platelet inhibitor (or an anti-platelet drug).

For example, the dose (or frequency) of platelet inhibitor (or an anti-platelet drug) may be increased if the genotype determined for the subject indicates that the subject has highly responsive platelets. Alternatively, the dose (or frequency) of platelet inhibitor (or an anti-platelet drug) may be decreased if the genotype determined for the subject indicates that the subject has poorly responsive platelets and may be prone to bleeding if too much drug is adminstered.

The prophylactic or treatment may be specific for adenosine-di-phosphate (ADP)- stimulated platelet activation, collagen-related peptide (CRP)-stimulated platelet activation, or ADP- and CRP-stimulated platelet activation.

Embodiments of the invention are described in the Example below, with reference to the accompanying drawings and tables, in which:

Figure 1 shows: The distribution of minor allele frequencies for the single nucleotide polymorphisms (SNPs) before and after resequencing of the exons and their flanking intronic sequence and the sequencing of the highly conserved non-coding regions for the GP6 and ITGA2 genes.

A total of 1989 SNPs were identified with approximately half being new ones. The minor allele frequencies (MAFs) are shown on the X axis. The upper and lower panels show the distribution of MAFs before and after resequencing, respectively. As expected, there is a major enrichment for SNPs with lower MAFs.

Figure 2A shows: The P values of the Single Nucleotide Polymorphisms for the 30 loci with an association signal.

Two sets of three graphs are shown, the upper set shows the level of P-selectin expression and the lower set the level of fibrinogen binding (see for detail ⁶J. The loglO P value is presented on the Y axis. The chromosomal location, position in Mb, the direction of the transcript (5' to 3' + and 3' to 5', -), the chromosomal position (in Mb) and the length of the locus (in kbp) are presented on the X axis. The unique identifier of the SNP with the lowest P value (rs number or NT number) is also given on the X axis. SNPs are grey symbols if P value > 0.005 and closed symbols if < 0.005. Circles represent synonymous SNPs and triangles represent non-synonymous SNPs (SNPs which alter the amino acid sequence of the protein). Diagrams of gene structure are given with vertical lines representing exons.

Figure 2B shows: Each of the 30 figures has two rows of three box plots showing the association between SNP genotype and functional response to ADP and CRP.

Two sets of three graphs each are shown, the upper set shows the level of P-selectin expression and the lower set the level of fibrinogen binding on the Y axis (for detail, see ⁶). The left column shows P-selectin expression and fibrinogen binding after ADP stimulation (PA and FA, respectively). The middle column provides the same but for CRP (PC and FC) and the right column shows the data from the middle column but after correction for the confounding effect of the GP6 locus (PC and FC, GpVI adjusted). The unique SNP identifier (rs number or NT number) is shown at the bottom left corner of the graph, the P value at the top right comer of each of the six graphs and the effect size (extent of change) is at the top left corner of each graph with the direction of the effect indicated by + (minor allele is the risk allele for enhanced platelet function) and - (major allele is risk allele for enhanced platelet function). The number of homozygotes for the major allele, heterozygotes and homozygotes for the minor allele are presented below the graph at the bottom right corner.

Figure 3 shows: The ADP and CRP signallomes have been visualised by Cytoscape using first-order protein-protein interaction data from Reactome and IntAct using the proteins encoded by the candidate genes as drivers.

A total of 99 proteins (nodes) and 144 edges have been placed in the network at their presumed location in resting platelets. For each of the 30 genes for which an association between sequence variation and platelet function had been observed (Table 1C) the best P value is visualised by surface area of the node by inverted correlation, with nodes modifying i) the ADP response as squares, ii) the CRP response as circles, and iii) both the ADP and CRP response as triangles. The grey colour scale of the nodes from light to dark indicates the relative level of the transcript for the node in megakaryocytes, with blank symbols indicating the lack of a probe on the ϋlumina microarray Version 2 platform.

Table IA: The table shows the HUGO names of the 108 genes which were genotyped in the 506 DNA samples from the platelet function study cohort. The second column provides the number of tag-SNPs per gene.

Table IB: The table shows the number and consequences of the SNPs detected in the exons and flanking intronic sequence of the 108 genes which were resequenced in 48 Caucasoid CEPH DNA reference samples.

Table 1C: The table shows the HUGO names of the 30 genes for which an association was observed between sequence variation and platelet function. For each gene the SNP is presented which has the best P value or which belongs to a group of SNPs with similarly low and good P values. For each SNP the nucleotide for the major and minor allele are given in Adenine(A), Cytosine(C), Guanine(G), and Thymine(T). and the minor allele frequency (MAF) observed in the PFS-506 cohort is given. The allele which enhances the platelet response to agonist (being ADP or CRP) is called the 'risk allele' and is coded as Al for the major allele and A2 for the minor one. The measurement channel affected by the sequence variation is coded as ADP₅ CRP or both (also see Figures 2A and 2B). SNPs are uniquely identified by their rs number. The two SNPs without an rs number have been given an internal reference number, NT (see Table ID). SNPs with rs numbers are unequivocally mapped to the genomic sequence and rs numbers generally do not alter with sequential genome builds. In the case rs numbers are changed then a audit trail is maintained in publically accessible databases.

Table ID: The table presents the two SNPs from Table 1C which do not have an rs number. The NT number is an internal reference number for SNPs identified and assigned by the Wellcome Trust Sanger Institute. The position of the NT SNPs in the genome is unequivocally identified by the flanking sequence which is provided in this Table.

Table IE: Genotyping results for 1536 SNPs in the 506 samples of the PFS study are shown.

Example

Gene Sequence Variation and Platelet Function

A priori selection of 97 candidate genes

Candidate genes (Table IA) were selected on basis of a priori knowledge of the importance of corresponding proteins in the ADP and CRP signalling pathways. Another 10 genes were added to the list of candidate genes on the basis of the outcome of the microarray study. The list of 108 candidate genes and the number of tag-SNPs per locus are shown in Table IA. The 97 genes/proteins which were selected on a priori knowledge are deemed specific either for the ADP pathway, for the CRP pathway or for both. Information on SNPs in the 97 genes was increased to 1969 SNPs in total by the sequencing of the exons and flanking intronic sequences (and in highly conserved non-coding regions for ITGA2, ITGBl, GP6 and CDl 09) in 48 Caucasoid DNA reference samples from the Centre d'Etude Polymorphism Humaine (CEPH). This sequencing effort lead to a near doubling of the number of SNPs beyond what was known at the time of the experiment in the international data registry (dbSNP, http://www.ncbi.nhn.nih.gov/proiects/SNP/ ¹⁷ and Table IB). The spectrum of minor allele frequencies (MAFs) of the 1969 SNPs showed a substantial left shift with a particular enrichment for MAFs < 0.1 (Figure 1). Analysis of the consequences of the SNPs on protein structure showed evidence of 96 SNPs which altered the amino acid sequence, so called non-synonymous (ns) SNPs. The mapping of the consequences of the nsSNPs to the position of the amino acid in the respective protein is hampered by the fact that many genes have multiple transcripts. It is currently unknown to us and others for genes with multiple transcripts which transcript is the most abundant and functionally important transcript in megakaryocytes and platelets. A small number of SNPs may possibly lead to alternative splicing of the transcript. The limitations on the exact mapping of nsSNPs is not relevant to the associations reported here because the position of the SNP is specified by its position in the genomic sequence by the rs or NT number (Table 1C and ID).

Genotyping of the 506 DNA samples from the PFS cohort

A purpose-designed Illumina Golden Gate genotyping platform for 1536 SNPs was ordered for the genotyping of the 506 DNA samples from the PFS cohort. The selection of SNPs was based on the following criteria: i) all SNPs identified by the exon resequencing were included on the platform, but if a pair of SNPs was in linkage disequilibriuϊn (LD) with a R² > 0.9 then one SNP of the pair was removed, ii) 10 genes from a microarray study (see below) were not resequenced and the tag-SNPs were selected on basis of HapMap information ¹⁸, iii) for four genes {CD109, GP6, ITGA2, ITGBl) additional SNPs tagging the highly conserved non-coding regions were included ¹⁹.

The statistical analysis of the association between SNP alleles and the platelet cellular response to ADP and CRP-XL was based on 1494 tag-SNPs (42 tag-SNPs were removed). A linear regression analysis showed robust evidence at P values < 0.005 for 20 genes (Table 1C) and 10 additional SNPs with P values > 0.005 but < 0.01 (Table 1C). The P values for the level of association ranged from statistically highly significant effects e.g. rsl613662 for the GP6 gene (best P value 0 for P-selectin expression after stimulation with CRP) to 0.0095 for rs 16994453 in the PLCBl gene which was only apparent after correction of the effect of the GP6 locus. For some loci the observed association between cellular function and SNPs are single point observations, e.g. rs350916 in the MAP2K2 gene shows a robust P value of 0.0014 but the other five tagSNPs in the same locus do not show a significant association signal (Figure 2A). The location of the SNPs in relation to the gene structures and the respective P values for the four functional read-outs is shown in Figure 2 A (graphs 1- 30). In Figure 2B for CRP two sets of results are presented, uncorrected and corrected for the effect of the GP6 locus. The latter set of results has a greater reliability to identify small effects from other genes in the CRP response channel as it removes possible confounding effects caused by the sequence variation at the GP6 locus.

Low minor allele frequency

For six SNPs the MAF was < 0.03 and for another six < 0.1. For these 12 SNPs with low MAFs the association was generally based on the analysis of the difference in the functional response between platelets from individuals homozygous for the major allele and those from heterozygous individuals (see Figure 2B for numbers of individuals in each of the genotypic categories).

212 of the 346 SNPs with a MAF < 0.05 were identified by the resequencing of the exons and the flanking intronic sequence (these are identified by NT number in Table 1C) and 9 of the 30 SNPs which showed a significant association (Table 1C) were newly identified NT SNPs (AKT2, GAS6, GNA12, ITGA2, ITPRl, MADD, MAP2K4, GNAZ, VAV3). Two of the 'NT' SNPs in the GNAZ gene (NTJ)11520.10_2802586) and the VAV3 gene (NT_019273.17_4225076) respectively have no 'rs' numbers assigned yet (Table ID). The position of these two SNPs has been unequivocally defined by the 3' and 5' flanking genomic sequence which is provided in Table ID (SEQ ID NO: 1 relates to GNAZ; SEQ ID NO: 2 relates to VAV3).

Direction of effect

Enhanced platelet responsiveness to ADP, CRP or to both is assumed to be a relative risk for thrombosis. SNPs which have a significant association with one or more of the cellular functions will show a direction of effect (Figure 2B). In other words, the level of response may be enhanced in individuals who carry the major allele or vice versa in individuals carrying the minor allele. The direction of the effect is expressed as the beta value which is plotted at the top left corner of each of the six graphs in Figure 2B. The association between sequence variation can be observed in a single measurement channel (e.g. fibrinogen binding upon CRP activation) or several channels (e.g. both fibrinogen binding and P-selection expression after CRP activation). Alternatively, an association can be agonist specific (only observed with ADP or only with CRP) or occur with both signalling pathways. An overview of the results can be obtained from Table 1C and Figures 2A and 2B.

Risk allele

In Table 1C the allele conferring increased platelet reactivity was named the 'risk allele'. The major and minor alleles have been coded as Al and A2, respectively (Table 1C). For 18 genes the minor allele (A2) is the risk allele and for the remaining 12 it is the major allele. There are also examples where different SNPs in the same locus show association with function with opposing beta values. This phenomenon has been observed in several association studies and illustrates that the SNPs are most likely not in LD and report on different causative mechanisms. A clear example is the P2RY12 gene where the major allele of rsl472122 (MAF 0.483) is a risk allele, whilst for rsl 0935839 (MAF = 0.355) the minor allele is the risk allele (Figure 2A).

The signalling cascades

The signalling cascades for ADP and CRP are assumed to be distinct for the receptor proximal segments of the pathways. There is therefore minimal cross-talk between the two pathways for the molecular events before the release of Ca²⁺ from the intracellular stores. After Ca²⁺ release the ADP and CRP signalling events are common but too diverge for a large extent distinct for the change in the configuration of αllbβ3 (Glycoprotein [GP] Ilbllla), allowing fibrinogen binding to occur which was one of the functional read-outs) and for the expulsion of α granules leading to the expression of P-selectin (the second read-out). The association results between platelet function and genotypes are in support of this notion and the sequence variation in 14 (GNAZ, ITGA2, JAK2, MADD, MAP2K1, MAP2K2, MAP2K5, MAPK14, P2RY12, PFKL, PTGS2, RAFl, VAV3, ITPRl), 11 (AKT2, CD36, CDC42, FCERlG, GNA12, GP6, INSR, MAP2K4, TBXASl, VAVl, LAT) and 5 genes (C0MMD7, GAS6, PEARl, PLA2G2A, PLCBl) are associated with the ADP, CRP or both responses respectively (Table 1C).

The 'first order' interaction of the proteins encoded by the 97 genes which were on the a priori candidate gene list was determined by using Reactome and IntAct protein- protein information and a programme application called Cytoscape. Information on connectivity and interdependency between the pathways were obtained from the two databases for ~ 50% of the proteins. The results from the network analysis are depicted in Figure 3. In this figure the lines indicate 'first order' connectivity between proteins (nodes), the surface area of the node is inversely correlated with the P value of the association between platelet function and genotype and the 'grey' intensity of the node indicates the transcript level of the corresponding genes in megakaryocytes.

Addition of genes/proteins identified from a microarray experiment allowed expansion of the network to one of 409 hubs and 424 edges. The nodes identified in the microarray experiment or which were present in the a priori candidate gene list have been visualised as squares and the those identified by the microarray experiment as squares, respectively. Diamond shaped nodes are present in both lists. Grey intensity shows the transcript level of the nodes in megakaryocytes. One highly connected node or so called hub is EGFR, a protein which gene is known to not be transcribed in megakaryocytes or other haematological lineages. Absence of this hub is incompatible with network stability as shown and we postulate on the basis of structural analysis that in megakaryocytes the EGFR protein is replaced by PEARl, an EGF domain containing platelet membrane protein which was in the a priori candidate gene list. Alternatively and based on inspection of the other hubs in the EGFR cluster, the MPL protein may be the replacement of EGFR in megakaryocytes. Proteomics studies and immunoblots are required to validate the suggested EGFR replacements. Discussion

In conclusion we have identified for the first time in a systematic manner a number of genes which modify platelet function. The selection of the 97 candidate genes on a priori knowledge of their importance in ADP and CRP signalling cascades has been on the basis that a substantial number of positive associations have been observed. At a relaxed statistical cut-off, sequence variation in 30 genes showed an association with the platelet functional phenotype. A stricter statistical cut-off of 0.005 and below reduces this number to 20. Figure 2A shows the P value for all SNPs at the locus level. These figures illustrate that for several but not all genes multiple SNPs produce the same and significant P value (e.g. GP6 locus). This is most likely explained by a high LD between the SNPs or alternatively for a pair of SNPs with different MAFs the one with the low MAF may have a high D value with the SNP with the higher MAF.

Table 1A: ( Series in association study and number of tag-SNPs

I H- IE I I c: O C p a 2

O C p C Q

Q Q

O 2. O a Q

O O G) CD

O 2. O ω W a

W ω CΛ

Z 2 Q) Z O) Z Q) Z

3 ^■υ 3 Tl 3 Tl 3 Tl 3 Tl

1-22 fϊQ 23-44 $36 45-66 231 67-88 314 89-108 227

AKT1 5 GNA12 10 LCK 3 PIK3CB 6 PTPN11 5

AKT2 8 GNA13 2 LC P2 12 PIK3CG 11 PTPN6 5

ALDOA 7 GNAI2 5 LDLR 19 PIP5K3 17 RAC1 8

ARHGEF1 4 GNAI3 6 LYN 8 PLA2G2A 5 RAF 1 7

BAD 1 GNAQ 3 MADD 16 PLA2G4A 10 RHOA 2

BC L2 6 GNAS 6 MAP2K1 8 PLCB1 39 SELP 13

BTK 16 GNAZ 8 MAP2K2 6 PLCG2 26 SHC1 4

CALM1 7 GP6 42 MAP2K3 5 PLSCR 1 2 SYK 17

CALR 1 GRAP2 5 MAP2K4 4 PPP2CA 7 TACC3 16

CD109 60 GRB2 3 MAP2K5 9 PRKACB 34 TBPL1 28

CD36 41 GRP58 7 MAP2K6 7 PRKCA 1 TBXA2R 1

CD9 6 GTF2A2 14 MAPK1 11 PRKCB1 21 TBXAS1 19

CDC42 41 ILK 5 MAPK11 2 PRKCD 10 TEC 12

C0MMD7 10 INSR 31 MAPK14 11 PRKCE 30 THBS1 10

CSK 10 IRS1 5 MPL 5 PRKCG 8 TLN 1 38

F2R 2 ITGA2 111 MYLK 27 PRKCH 13 TUBB1 4

F2RL3 6 ITGA2B 2 NFE2L2 30 PRKCQ 11 VAV1 8

FCER1G 6 ITGB1 45 P2RX1 3 PTGS1 11 VAV3 18

FYB 9 ITGB3 49 P2RY1 1 PTGS2 6 VIPR1 12

FYN 7 ITPR1 61 P2RY12 20 PTK2 19

GAS6 13 JAK2 10 PECAM1 9 PTK2B 27

GNA11 12 LAT 6 PEAR1 15 PFKL 31

SNP, Single Nucleotide Polymorphism

No of SNPs, number of tag-SNPs to test the I OCUS for sequence i variation

Number of genes and SNPs/gene alternate between uneven and even columns

HUGO names have been used to identify genes

GNA12 2 NT_007819.15_2064696 rs41304915 A T A2 CRP 0.001 0.6910 0.0000 0.7437 0.0000 0.0000 0.0000 0.0000

FCER1G 3 rs3557 G T A1 CRP 0.095 0.7920 0.0001 0.7377 0.0000 0.0001 0.0000 0.0000

CD36 4 rs1049654 T G A2 CRP 0.441 0.3555 0.0030 0.9436 0.0704 0.0013 0.1010 0.0013

AKT2 5 NT_011109.15_13006313 rs41275750 C G A2 CRP 0.066 0.2988 0.0125 0.7528 0.0967 0.0016 0.0623 0.0016

MAP2K4 6 NT_010718.15_11625033 rs41307923 G A A1 CRP 0.008 0.3326 0.0072 0.6558 0.0026 0.0062 0.0028 0.0028

LAT 7 rs1802141 G A A1 CRP 0.015 0.7984 0.3390 0.0415 0.0340 0.0967 0.0058 0.0058

VAV1 8 rs 186295 T C A1 CRP 0.124 0.5336 0.0461 0.9785 0.0152 0.0213 0.0068 0.0068

TBXAS1 9 rs2072179 G A A1 CRP 0.044 0.4887 0.0060 0.9154 0.0032 0.0153 0.0080 0.0080

INSR 10 rs6510959 T C A1 CRP 0.165 0.4802 0.4916 0.3170 0.7066 0.0090 0.0813 0.0090

CDC42 11 rs7544500 G A A2 CRP 0.384 0.7916 0.3826 0.1886 0.1219 0.0269 0.0093 0.0093

SNP, Single Nucleotide Polymorphism

FA, fibrinogen binding to ADP stimulated platelets

FC, fibrinogen binding to CRP stimulated platelets

PA, P selectin expression on ADP stimulated platelets

PC, P selectin expression on CRP stimulated platelets

K* ADP, adenosine-di-phosphate

O

CRP, cross-linked collagen related peptide

A1, major allele;A2, minor allele

No rs number, see Table 1C

The horizontal line between MAP2K1 and LAT indicates the split of the P value at Q.005

Table ID:

Table 1E: Results of genotyping for 1536 SNPs ir I 506 samples

SNP A- I A2 MAF NM P values Minimum

PA PC FA FC I PCac§ I FCad) P value

AKT1 rs24S8796 A G 0295 994 0023 0188 0118 0276 0228 0390 0023

Aκri C G 0431 994 0108 0936 OSOO 0500 0898 0397 0108

AKT1 NT.026437 11_B6237422 A G 0028 994 0249 0526 0814 0 126 0624 0119 0119

AKT1 rs2494735 C T 0060 992 0886 0041 0486 0 111 0 198 0377 0198

AKT1 NT_02643711_88245e96 T C 0080 994 0711 0754 0727 0886 0687 0.637 0637

AKT2 NT_01110915_13006313 C G 0066 994 0.299 0013 0753 0097 0002 0.062 0002

AKT2 rs3730055 A G 0068 986 0333 0024 0658 0 145 0003 0088 0003

AKT2 rs37300S1 C T 0.253 994 0031 0.298 0391 0318 0525 0532 0031

AKT2 NT_01110915.13007731 C T 0.492 994 0060 0.563 0666 0883 0275 0643 0060

AKT2 rs1298O463 A G 0002 994 0730 0448 0 168 0323 0619 0456 0 168

AKT2 NT_01110915_13006637 A T 0.004 994 0524 0866 0919 0827 0543 0985 0524

AKT2 ra1804324 O A 0.000 994

AKT2 NT.0111091S_130155BO O G 0000 994

ALDOA rs2278S57 G C 0.403 994 0565 0688 0087 0408 0498 0267 0087

ALDOA rs9783783 G C 0494 992 0509 0478 0 104 0271 0353 0190 0104

ALDOA rs8054507 A G 0466 994 0483 0654 0213 0527 0518 0422 0213

ALDOA rsS928448 G A 0471 994 0372 0713 0221 0561 0516 0410 0221

ALDOA rs3809624 G A 0322 994 0919 0746 0821 0796 0244 0388 0244

ALDOA «8049837 A G 0066 994 0510 0925 0347 D 619 0979 0599 0347

ALDOA rs2289291 O G 0000 994

ARHGEFI NT_01110915_14678841 C G 0003 994 0934 0139 0934 0384 0058 0316 0058

ARHGEFI NT.01110915_14ST7554 G T 0010 994 0982 0764 0229 0417 0425 0.213 0213

ARHGEFI NT_01110915_14661037 G C 0001 994 0969 0751 0823 0647 0976 0849 0823

ARHGEFI NT_01110915_14660555 O G 0000 994

BAD NT.0339037_9357618 T C 0043 994 0731 0802 0885 0492 0417 0231 0231

BCL2 rs4987856 T C 0117 994 0628 0309 0899 0 126 0094 0037 0037

BCL2 rs498784S T C 0117 994 0628 0309 0899 0 126 0094 0037 0037

BCL2 NT.02502813_8583521 A G 0003 994 0571 0 331 0213 0864 0691 0655 0213

BCL2 rs1016860 T C 0111 994 0754 0958 0324 0538 0871 0624 0324

BCL2 NT_02502813_8586164 A C 0005 994 0510 0651 0756 0648 0453 0679 0453

BCL2 rs1564483 A G 0235 994 0610 0543 0669 0643 0633 0756 0610

BTK TS2238983 C T 0074 994 0028 0032 0 100 0216 0168 0668 0028

BTK rs7884209 C A 0128 994 0069 0 126 0 132 0217 0343 0476 0069

BTK rs2855259 A G 0251 994 0955 0081 0 244 0015 0396 0077 0077

BTK rs12848641 C G 0 157 994 0081 0 139 0 574 0461 0179 0688 0081

BTK rs1053870 T G 0142 994 0146 0 105 0 124 0174 0334 0433 0124

BTK rs3027594 G T 0 102 994 0608 0568 0 3O6 0339 0277 0160 0160

BTK rs2071222 T C 0225 994 0957 0281 0 942 0 140 0362 0 195 0195

BTK rs2S15901 T C 0226 994 0841 0276 D 912 0 155 0349 0219 0219

BTK rs700 T G 0481 994 0453 0035 0 7O4 0037 0252 0224 0224

BTK rs2239461 T C 0350 992 0345 0701 0415 0835 0888 0841 0345

BTK re5951303 C T 0345 968 0359 0 546 0372 0661 0719 0815 0359

BTK T C 0064 990 0785 0698 0620 0835 0365 0783 0365

BTK rs2071223 C T 0318 994 0816 0384 0415 0388 0657 0671 0415

BTK rs2238985 T G 0205 992 0931 0317 0799 0347 0519 0533 0519

BTK rs2071229 A G 0062 994 0796 0861 0 530 0441 0709 0628 0530

BTK rs1023431 T G 0104 994 0756 0574 0548 0535 0966 0853 0548

CALM1 rs2300499 C G 0063 994 0601 0074 0 537 0 197 0086 0283 0086

CΛLM1 rs2300497 T C 0 104 992 0784 0 151 0 900 0204 0093 0187 0098 CALMI re3729787 T C 0015 994 0 158 0712 0366 0378 0409 0212 015B

CALM1 ra2300500 G C 0410 994 0.235 0331 0866 0351 0621 0607 0235

CALMi rs2268433 G A 0.347 994 0331 0914 0626 0750 0724 0993 0331

CALM1 NT_02643711_71865380 G A 0.221 992 0504 0.263 0359 0225 0480 0395 0359

CALM1 NTJJ2643711_71863451 O A 0000 994

CALR NT_01129510_4312176 A G 0002 994 0807 0702 0.013 0181 0691 0146 0013

CD109 rs3O12541 C T 0060 994 0936 0268 0014 0014 0334 0011 0011

CD109 rs1437579 C T 0046 994 0996 0626 0018 0048 0337 0012 0012

CD109 NT.00729912_12347216 G T 0047 994 0013 0194 0468 0572 0372 0949 0013

CD109 NT.00729912_12301359 A G 0002 994 0029 0818 0312 0554 0405 0255 0029

CD109 rs693O164 C G 0039 994 0861 0850 0032 0 144 0514 0050 0032

CD1O9 rs28360541 G T 0438 994 0388 0559 0237 0627 0233 0040 0040

CD109 NT.0072Θ9 12J2333325 A G 0031 994 0047 0.224 0173 0176 0147 0116 0047

CD109 «7774274 A C 0482 994 0391 0661 0163 0459 0376 0048 0.048

CD109 «4708090 T C 0187 994 0326 0412 0161 0196 0144 0062 0062

CD109 fs773945S A T 0.481 986 0180 0905 0083 0729 0385 0.237 0083

CD 109 rs8453696 C T 0464 994 0426 0701 0645 0337 0166 0069 0089

CD 109 rc9442951 G A 0478 994 0494 0719 0473 0602 0310 0076 0076

CD109 rs104S5097 T G 0487 994 0481 0710 0539 0321 0212 0079 0079

CD109 NiT_00729912_12232059 C G 0004 994 0892 0100 0900 0243 0080 0268 0080

CD109 NT.00729912_12388362 G A 0004 994 0892 0100 0900 0.243 0080 0268 0080

CD109 rs9293938 A C 0283 994 0547 0757 0200 0.298 0316 0086 0086

CD109 NT.00729912_1217823O T C 0027 994 0416 0065 0159 0.236 0094 0362 0094

C0109 rS4708089 G A 0481 994 0542 0559 0851 0267 0243 0106 0106

CD109 rs2917862 T C 0466 994 0858 0739 0110 0378 0636 0743 0110

CD109 rs1392913 G A 0369 994 0321 0542 0508 0292 0226 0.115 0 115

CD109 rs2351311 A G 0495 994 0243 0691 0476 0263 0392 0116 0116

CD109 rs6923034 C T 0334 994 0679 0716 0576 0830 0281 0 152 0152

CD10S NT_O0729912_12346024 A G 0007 994 0583 0 148 0813 0181 0152 0201 0152

CD109 rs10805974 C G 0378 994 0 176 0849 0259 0510 0284 0156 0 156

CD109 rs9343O83 C T 0060 994 0.250 0398 0280 0910 0571 0160 0 160

CD109 rs944295β G A 0331 S94 0628 0676 0571 0359 0332 0162 0162

CD10β rs4342388 T G 0369 994 0.293 0556 0610 0340 0276 0166 0 166

CO109 rs4708077 C G 0333 994 0768 0634 0535 0869 0371 0204 0204

CD109 rs4706554 T C 0487 994 0786 0953 0823 0669 0351 0209 0209

CD10S ra47080β8 A G 0358 994 0218 0809 0472 0616 0336 0281 0218

CD1D9 rs5023688 A G 0350 994 0317 0775 0723 0540 0296 0218 0218

CD109 rs3012558 A G 0419 994 0303 0823 0232 0690 0609 0802 0232

CD109 rs3012572 T C 0373 994 0603 0419 0251 0 166 0863 0501 0251

CD109 NT.00729912_12296273 T C 0107 994 0729 0353 0946 0 187 0524 0262 0262

CD109 rs2882694 T G 0382 994 0859 0487 0264 0.288 0968 0617 0264

CO109 rs1370436 C T 0371 994 0890 0823 0265 0725 0469 0684 0265

CD109 rs1898485 G T 0316 990 0813 0244 0740 0374 0270 0430 0270

CD109 T C 0225 994 0411 0974 0342 0572 0605 0278 0278

CD109 rs9352023 C A 0 157 994 0343 0547 0781 0755 0741 0498 0343

CD109 rs6901628 T C 0249 992 0423 0811 0590 0610 0440 0344 0344

CD109 rs9446976 C T 0395 994 0483 0980 0344 0678 0962 0577 0344

CD109 rs7774119 A C 0318 994 0628 0961 0859 0793 0359 0349 0 349

CD109 TS1992141 C T 04S0 994 0922 0912 D 473 0936 0365 0503 0 365

CD109 NT_00729912_12317992 A G 0063 990 0884 0310 0399 0239 0955 0639 0399

CD109 rs38467S5 G T 0 175 994 0960 0912 0863 0469 0903 0424 0424

CD109 rs4708076 G A 0099 S94 0445 0434 0588 0900 0731 0705 0446 CD109 ra10943122 T C 0313 994 0525 0702 0886 0764 0645 0.707 0525

CD109 rs1O498893 T G 0312 994 0535 0.730 0978 0787 0633 0696 0535

CD109 rs1876700 A T 0305 992 0631 0955 0541 0752 0660 0996 0541

CD109 NT_00729912_12210174 A G 0284 0914 0735 0561 0986 0543 0883 0543

CD109 153764240 T C 0053 994 0680 0437 0567 0505 0909 0919 0567

CD109 rs159534β G A 0327 994 0811 0655 0683 0709 0575 0671 0.575

CD109 rs300549S C A 0181 994 0641 0703 0708 0886 0846 0957 0641

CD109 NT.007299 12_1225S977 C T 0086 994 0918 0731 0880 0332 0669 0657 0657

CD109 ra2351127 T C 0090 994 0706 0745 0718 0710 0788 0938 0706

CD109 [S3751645 G T 0330 994 0849 0422 0721 0535 0759 0772 0721

CD109 re9446983 o c 0000 994

CD1O9 NT_00729912_12293437 O A 0000 992

CD109 NT_00729912_12295889 O T 0000 994

CD38 rs1049554 T G 0441 994 0356 0003 0944 0070 0001 0101 0001

CD36 [53211822 A G 0373 0488 0016 0328 0088 0001 0040 0001

CD36 [5819437 A G 0445 994 0422 0002 0535 0032 0002 0067 0002

CD36 rs20S566β A G 034S 994 0985 0005 0254 0014 0002 0013 0002

CD36 rs6972923 C G 0380 994 0594 0011 0173 0043 0003 0032 0003

CD36 rs7806711 C A 0337 994 0924 0003 0129 0005 0003 0009 0003

CO36 rs1761661 G T 0446 994 0418 0003 0679 0041 0003 0091 0003

CD36 «17154155 A C 0411 994 0828 0003 0947 0033 0004 0079 0004

CD36 rs69β10S9 T C 0.398 992 0906 0001 0906 0010 0005 0050 0005

CD36 rs997906 0350 994 0881 0015 0521 0046 0006 0040 0006

CD36 rs7755 T C 0424 0512 0036 0739 0144 0007 0088 0007

CD36 rs1761645 T A 0472 994 0380 0011 0703 0081 0008 0079 0008

CD36 rs10480808 A T 0422 988 0965 0004 0842 0049 0009 0133 0009

CD36 rs7779873 A G 0439 0716 0011 0880 0053 0010 0084 0010

CD36 re10215288 C 0030 994 0012 0575 0090 0838 0244 0539 0012

CD36 rs10954289 C T 0436 0542 0084 0625 0303 0016 0168 0016

CD36 [510246832 C 0141 994 0024 0038 0253 0416 0099 0841 0024

CD36 [S3212000 C G 0031 994 0031 0083 0 12S 0160 0071 0187 0031

CD36 [S1S37593 T C 0099 0043 0261 0731 0903 0411 0751 0043

CD36 rs1924 G 0068 994 0647 0207 0073 0788 0699 0527 0073

CD36 rs819439 A G 0032 0078 0654 0086 0785 0425 0595 0076

CD36 TS3212013 G 0046 994 0144 0055 0226 0047 0089 0082 0082

CD36 rs9641866 A 0067 994 0641 0240 0085 0794 0865 0469 0085

CD36 [S3173798 G A 0067 994 0641 0240 0085 0794 0665 0469 0085

CD36 NT_007933 14_5539848 A G 0116 994 0833 0332 0340 0092 0413 0105 0105

CD36 rs11772036 T C 0064 972 0522 0323 0 108 0901 0921 0445 0108

CD36 [S1O499858 C T 0062 0502 0294 0 129 0875 0773 0525 0129

CD36 TS1334511 G 0065 992 0994 0334 0 131 0779 0960 0558 0131

CD36 [S11974777 G T 0058 0774 0415 0 137 0963 0 S11 0489 0137

CD36 [S1527480 C T 0079 0449 0743 0346 0791 0412 0222 0222

CD36 rs3211879 T A 0054 994 0599 0076 0270 0 110 0 338 0358 0270

CD36 rs3211876 G A 0032 S94 0816 0385 0620 0803 0922 0288 0288

C036 [S321200S C T 0002 994 0974 0806 0909 0587 0350 0752 0350

CD36 [S321190B A G 0042 994 0788 0247 0379 0573 0994 0648 0379

CD36 rs1026S717 G A 0133 0391 0534 0542 0257 0934 0620 0391

CD36 [S3212O01 C 0025 994 0437 0 S07 0918 0851 0868 0566 0437

CD36 rs1527483 T C 0072 0971 0 315 0 S04 0622 0952 0710 0710

CD36 rs17154186 0000

CD36 rs3211890 0000 994 CD36 NT_0795161_7661548β O A 0.000 994

CDS rs3181290 T C 0.023 994 0806 0777 0140 0749 0.959 0499 0.140

CO9 NT_0097S91S_6189291 A T 0001 994 0161 0785 0789 0412 0920 0542 0161

CO9 rs796β772 A G 0013 992 0414 0696 0.230 0826 0654 0775 0230

CD9 rs3181301 G T 0454 994 0.444 0122 0824 0251 0360 0561 0360

CD9 rs2072372 G T 0.452 994 0483 0.150 0731 0268 0371 0532 0371

CD9 NT_009759 15_6188446 O G 0000 994

COC42 «7544500 G A 0384 988 0792 0383 0189 0122 0027 0009 0009

CDC42 rs6698486 T C 0256 994 0999 0848 0.152 0213 0124 0016 0016

CDC42 rs2473317 C G 0128 994 O 01B 0.780 0 102 0357 0589 0.737 0018

CDC42 re1O799719 G A 0409 992 0847 0739 0192 0.294 OOES 0023 0023

CDC42 rs2473277 C T 0469 994 0521 0114 0242 0.262 0.026 0129 0026

CDC42 rs1883421 G C 994 0048 0569 0652 0480 0696 0523 0048

CDC42 re1063116 T A 0251 994 0048 0569 0652 0480 0696 0523 0048

CDC42 f«2473307 T C 0481 994 0269 0.239 0298 0343 0063 0154 0063

CDC42 rs1474646 A G 0224 994 0089 0926 0620 1 000 0617 0684 0089

CDC42 rs25O1299 G A 0357 994 0661 0180 0739 0223 0093 0179 0093

CDC42 rs2OS6976 C T 0069 994 0095 0114 0998 0167 0358 0449 0095

CDC42 rs7412O1O C G 0177 994 0957 0269 0459 0291 0103 0.165 0 103

CDC42 rs4SO4857 A G 0028 994 0293 0987 0248 0327 0109 0944 0 109

CDC42 C G 0260 994 0769 0852 0.685 0398 0301 0115 0115

CDC42 A G 0079 994 0 120 0083 0770 0087 0346 0317 0120

CDC42 rs25O129S A G 0034 994 0374 0758 0197 0577 0.121 0809 0121

CDC42 rs226β177 A T 0187 994 0835 0364 0427 0441 0.123 0236 0123

CDC42 rs6672792 T C 0244 994 0137 0741 0694 0803 0906 0946 0137

CDC42 rs12410694 A G 0237 994 0138 0958 0532 0917 0464 0549 0138

CDC42 rs1545593 G T 0379 994 0931 0235 0498 0200 0141 0152 0141

CDC42 rs3768574 C T 0040 994 0857 0276 0538 0197 0190 0144 0144

CDC42 ra25O1285 T C 0040 994 0 150 0549 0859 0226 0863 0483 0150

CDC42 rs25O1278 G T 0110 994 0179 0062 0580 0048 0231 0162 0 162

CDC42 rs3117048 T C 0348 994 0689 0425 0622 0357 0175 0.200 0 175

COC42 rs1274070S A G 0112 994 0202 0411 0863 0549 0414 0513 0202

CDC42 rs1534949 G T 0420 990 0222 0248 0248 0295 0235 0297 0222

CDC42 rs11582456 C T 0023 994 0318 0790 0900 0890 0234 0663 0234

CDC42 fs2092322 C 0459 994 0234 0378 0407 0528 0408 0584 0234

CDC42 rs6698084 A C 0390 994 0696 0517 0428 0331 0344 0241 0241

CDC42 rs10917139 T C 0137 994 0371 0034 0474 0026 0513 0268 0268

CDC42 rs12024382 C G 0066 994 0484 0781 0284 0646 0677 0945 0284

CDC42 re12751936 A G 0241 994 0291 0628 0798 0601 0314 0379 0291

CDC42 «10917152 T C 0128 994 0322 0061 0403 0043 0947 0516 0322

CDC42 rs4654783 A G 0296 994 0396 0598 0783 0482 0677 0986 0396

CDC42 rs7355161 G T 0 134 994 0651 0760 0748 0890 0430 0651 0430

CDC42 rs12025633 A G 0 122 994 0822 0884 0634 0943 0433 0725 0433

CDC42 rs12022453 A G 0085 994 0502 0805 0952 0378 0454 0842 0454

CDC42 rs16826588 C G 0027 994 0927 0563 0871 0230 0858 0466 0466

CDC42 rs107S3522 T C 0005 992 0932 0143 0709 0277 0488 0702 0488

CDC42 re17837965 G A 0046 994 0859 0717 0913 0827 0606 0797 0606

COMMD7 rsβ141803 G A 0181 994 0001 0026 0094 0040 0367 0379 0001

COMMD7 rs6058869 A G 0415 994 0109 0967 0 185 0964 0538 0 S81 0109

COMMD7 rs6087983 T G 0 171 994 0608 0245 0109 0320 0674 0751 0 109

COMMD7 rs2424905 G A 0 456 994 0 121 0776 0311 0817 0317 0455 0 121

COMMD7 rs2424895 C T 0462 994 0 149 0688 0208 0694 0283 0383 0 149 COMMD7 rs2424898 G A 0245 994 0661 0014 0837 0021 0 166 0188 0166

COMMD7 rs927239 G A 0377 994 0200 0553 0268 0469 0898 0713 0200

COMMD7 rs13044952 A C 0376 992 0.202 0593 0270 0495 0943 0826 0-202

COMMD7 rs2064933 T C 0222 994 0.711 0034 0904 0030 0356 0256 0256

COMMD7 rs6119935 C A 0215 994 0949 0053 0530 0068 0549 0.505 0505

CSK rs2229729 T C 0.006 994 0659 0593 0028 0762 0288 0964 0028

CSK ra8O33381 C T 0.271 994 0792 0137 0939 □ 133 0210 0215 0210

CSK re1378940 C A 0331 994 0836 0329 0753 0208 0747 0432 0432

CSK re7035 T C 028S 994 0905 0436 0938 0.531 0462 0611 0482

CSK NT_01019416_45884630 T C 0013 994 0983 0.810 0903 0568 0579 0633 0579

CSK NT_01019416_4S873614 T C 0002 994 0 S38 0956 0593 0976 0815 0793 0.593

CSK rs2071S01 C A 0049 994 0829 0585 0786 0881 0890 0650 0650

CSK NTJM0194 16_45883740 T C 0011 994 0958 0300 0968 0548 0651 0997 0651

CSK NT_01019416_4S867227 C G 0.004 994 0713 0801 0918 0813 0901 0978 0713

CSK NT_010194 1B_45881205 O G 0.000 994

F2R NTJM6713 13_5422399 G A 0004 994 0986 0344 0199 0069 0849 0276 0199

F2R 135894 G T 0009 894 0591 0461 0476 034S 0310 0263 0263

F2RL3 rs773905 A G 0442 994 0032 0.250 0595 0359 0345 0503 0032

F2RL3 rs2608732 G C 0445 994 0094 0.271 0604 0322 0498 0542 0094

F2RL3 rs2227356 T C 0354 994 0 158 0912 0835 0990 0751 0891 0158

F2RL3 IS773903 A G 0200 994 0381 0269 0633 0318 0531 0582 0381

F2RL3 rs773902 T C 0199 994 0424 0.282 0695 0333 0518 0579 0424

F2RL3 ra222737β A G 0021 994 0.482 0765 0907 0937 0.810 OS63 0482

FCER1G rs3557 G T 0095 994 0792 0000 0738 0000 0000 0000 0000

FCER1G NT.0044Θ717_11679004 T C 0055 994 0301 0008 0253 0032 0029 0098 0029

FCER1G rs2070902 A G 0268 994 0124 0066 0680 0062 0055 0063 0055

FCER1G rs11587213 G A 0165 994 0734 0030 0174 0039 0147 0149 0147

FCER1G NT_OO44Θ7 17_11679746 G A 0002 994 0593 0842 0905 0426 0905 0505 0505

FCER1G NT_00448717_11679178 O T 0000 994

FYB rs379707 C A 0291 992 0884 0399 0589 0035 0883 0 127 0127

FYB rs3749740 C T 0026 994 0139 0332 0 192 0481 0550 0742 0139

FYB NT.00657615_39174860 T C 0002 994 0868 0883 0503 0794 0152 0522 0152

FYB rs4957132 G C 0290 994 0985 0625 0796 0092 0664 0246 0246

FYB rs394930 A G 0077 994 0809 0683 0495 0364 0665 0323 0323

FYB rs10059957 G A 0212 Θ94 0721 0560 0818 0097 0602 0327 0327

FYB NT_006576 15_39126286 A G 0157 994 0337 0601 0388 0598 0512 0581 0337

FYB rs377022 T C 0210 994 0868 0317 0760 0381 0624 0686 0624

FYN rs9384805 A C 0487 994 0030 0032 0348 0150 0046 0128 0030

FYN rs1022647 A G 0 145 992 0151 0628 0622 0669 0961 0998 0151

FYN rs6916861 G T 0 115 994 0307 0869 0374 0330 0674 0339 0307

FYN rs4947144 G C 0455 994 0308 0461 0483 0447 0932 0836 0308

FYN rs3752545 C A 0035 994 0415 0547 0653 0450 0758 0814 0415

FYN rs1801121 O A 0000 994

FYN NT_O25741 13_16193035 O C 0000 994

GASβ NT_0776272_115106 G C 0051 994 0966 0 156 0005 0034 0092 0017 0005

GAS6 NT_0776272_108589 A G 0033 994 0788 0104 0693 0 154 0020 0064 0020

GAS6 NT_0776272_103609 T C 0 148 994 0302 0687 0023 0719 0565 0641 0023

GAS6 NT_0776272_102251 T C 0008 994 0 167 0832 0060 0607 0841 0584 0060

GAS6 NT_0776272_115819 G A 0006 994 0746 0079 0656 0052 0 128 0082 0082

GAS6 rs8191975 G C 0077 994 0210 0677 0927 0748 0943 0579 0210

GAS6 A G 0047 994 0216 0822 0899 0634 0622 0988 0216

GAS6 NT 0776272 103544 A T 0021 994 0887 0347 0913 0 190 0449 0232 0232 GAS6 re1803628 A G 0 100 994 0740 0042 0446 D 094 0511 0622 0446

GAS6 rs96O4573 T C 0272 994 0813 0623 0717 0760 0661 0827 0661

GAS8 rs8191973 G C 0101 994 0847 0610 0969 0959 0.799 0.704 0704

GASβ NT_0776272_89027 O T 0000 994

GNA11 rs308040 G C 0494 994 0028 0817 06S7 0806 0541 0973 0028

GNA11 1.397454 T C 0130 994 0 118 0983 0.797 0714 0764 0798 0118

GNA11 rs308043 C G 0306 994 0221 0702 0512 0710 0473 0793 0.221

GNA11 NT_011255 14_3063887 A G 0010 994 0584 0517 0487 0979 0382 0989 0382

GNA11 NT_011255 14_3064111 T G 0022 994 0427 0916 0742 0969 0872 0926 0427

GNA11 re10402749 G A 0014 994 0482 0667 0563 0568 0433 0427 0427

GNA11 NT_O11255 14_3058064 A G 0.200 994 0460 0805 0517 0871 0605 0765 0460

GNA11 NT_011255 14_3058514 A G 0044 994 0518 0979 07β8 0995 0906 0931 0518

GNA11 rs3746089 T C 0 193 990 0519 0815 0671 0915 0710 0889 0519

GNA11 «7257368 C T 0350 994 0538 0791 0772 0782 0.698 0.804 0538

GNA11 NT_01125514_306213B 0 G 0000 994

GNA12 NT_0078191S_2084698 A T 0001 994 0691 0000 0744 0000 0000 0000 0000

GNA12 NT.CO781915_2064863 A G 0003 994 0001 0.250 0 107 0837 0017 0361 0001

GNA12 rs25276B6 C T 0447 994 0373 0043 0027 0 155 0074 0.295 0027

GNA12 re11772508 A C 0133 994 0969 0357 0045 0265 0212 0170 0045

GNA12 rs798532 A G 0289 994 0762 0.219 0.53S 0642 0063 0444 0063

GNA12 rs7805092 A C 0422 994 0799 0695 0192 0334 0963 0442 0192

GNA12 ra12484 T C 0420 994 0850 0800 0256 0326 0833 0464 0256

GNA12 rs7092B2 T C 0427 990 0376 0523 0265 0542 0631 0661 0265

GNA12 NT_00781915_2065701 A G 0003 994 0269 0194 0774 0217 0323 0374 0.269

GNA12 NT_00781915_2067103 O G 0000 994

GKIA13 NT_01078314_21778439 G A 0011 994 0605 0829 0452 0873 0345 0244 0244

GNA13 NT.01078314_21738458 C T 0048 994 0909 0755 0664 0558 0886 0801 0664

GNAI2 NT_02251716.50213280 A G 0050 994 0599 0046 0561 0136 0010 0077 0010

GNAK NT_022517 16_S0218098 G C 0 100 994 0692 0015 0764 0161 0058 0453 0058

GNAI2 NT_022517 17.50229322 T C 0005 994 0 125 0110 0353 0103 0249 0210 0 125

GNAI2 NTJ322517 17_50204710 T A 0010 994 0956 0085 0S09 0071 0373 0247 0247

GNAI2 1^9830408 G A 0029 994 0350 0378 0519 0583 0524 0804 0350

GNAI3 rs12721543 A G 0028 994 0 179 0765 0914 0501 0904 0676 0 179

GNAI3 NT_01927317_6214923 T C 0003 994 0963 0234 0921 0109 0465 0199 0199

GNAI3 rs2301230 A G 0498 994 0743 0140 0532 0155 0222 0232 0222

GNA13 rs1279195 A G 0 100 976 0931 0913 0641 0759 0398 0815 0398

GNAB rs3525 T A 0 171 994 0450 0580 0824 0431 0826 0599 0450

GNA13 NT_01927317_6222756 A T 0004 994 0855 0866 0889 0670 0940 0471 0471

GNAO πs2289121 C A 0307 994 0635 0073 0078 0013 0623 0118 0078

GNAQ NT_023935 17_9496841 A G 0008 994 0448 0389 0803 0641 0297 0622 0297

GNAQ NT_023935 17_9809850 O T oooo 994

GNAS rs234628 T C 0490 994 0723 0765 0681 O 700 0647 0.241 0241

GNAS rs3730168 A G 0319 994 0935 0881 0602 0424 0694 0254 0254

GNAS NT_0113628_22537219 G C 0002 994 0749 0782 0448 0456 0514 0.273 0273

GNAS rs7121 A G 0493 994 0580 0765 0281 0870 0920 0872 0281

GNAS rs919196 G A 0 189 994 0918 0482 0423 0863 0581 0639 0423

GNAZ NT.01152010_2802586 T C 0369 994 0001 0389 0188 0893 0 SS7 0571 0001

GNAZ rs9612234 G A 0451 992 0024 0071 0425 0140 0 181 0347 0024

GNAZ NT_01152010_2856690 G A 0002 994 0698 0266 0079 0658 0423 0980 0079

GNAZ rsi 1703490 G A 0021 994 0800 0 109 0724 0308 O OSO 0371 0090

GNAZ NT_011520 10_2829138 T C 0002 994 0970 0980 0097 0429 0371 0 122 0097

GNAZ NT 01152010 2828685 A G 0007 994 0840 0729 0 179 0934 0678 0440 0 179 GNAZ rs4820538 C T 0263 992 0933 0866 0780 0962 0362 0.558 0362

GNAZ rs1βO505β A G 0252 Θ92 0897 0988 0796 0873 0549 0781 0549

GP6 ra1613662 G A 0172 994 0090 0000 0675 0000 0000 0000 0000

GPβ NT_01110915_27807501 T C 0173 994 0099 0000 0658 0.000 0000 0000 0000

GP6 ra10424969 G T 0 110 994 0832 0000 0191 0000 0021 0013 0013

GP6 rs11667105 T C 0339 992 0015 0009 0396 0025 0.223 0369 0015

GP6 re1554410 G A 0494 994 0368 0000 0673 0001 0016 0120 0016

GPβ rs2124089 G C 0092 994 0746 0000 0457 0.000 0024 0017 0017

GP6 rs17836542 G C 0042 994 0593 0001 O207 0.000 0082 0028 0028

GPβ rs4806637 C T 0058 994 0463 0000 0 192 0000 0030 0039 0030

GP6 rs1043673 A C 0410 994 0041 0000 0859 0000 0943 0882 0041

GPβ rs1059211 A G 0230 994 0143 0320 0583 0295 0042 0 t88 0042

GPS rs11084382 A G 0228 994 0052 0000 0768 0000 0408 0303 0052

GP5 rs8113032 A G 0443 994 0501 0000 0062 0005 0304 0175 0062

GPB rs12981732 A G 0233 994 0064 0173 0.272 0.135 0080 0347 0064

GP6 re12973968 C G 0218 994 0111 0293 0377 0235 0069 0292 0069

GP6 rs1698θ158 G T 0086 994 0679 O 001 0147 0007 0071 0152 0071

GPβ rs11881471 A G 0 103 994 0351 0000 0080 0003 0 180 0.252 0080

GPβ rs1654439 T G 0 174 994 0089 0000 0827 0000 0536 019S 0089

GP6 rs1654504 A G 0223 994 0820 0000 0 130 ooαo 0096 0266 0096

GPβ ra1654416 G A 0187 994 0326 0000 0304 0000 0118 0454 0118

GPE rs1671150 T C 0190 994 0.283 O 000 0223 0000 0128 0358 0128

GP6 ra23O4167 C T 0 1S0 994 0283 0000 0223 0000 0128 0358 0 128

GPβ rs1671153 C A 0.190 994 0283 0000 0223 oo∞ 0 128 0358 0 128

GP6 ra16S4431 G A 0454 994 0985 0000 0253 0000 0 137 0.280 0137

GP6 rs1671169 A G 0232 994 0988 0000 0679 0000 0185 0142 0142

GPβ rs1671218 C T 0340 994 0 145 0000 0483 0000 0721 0753 0145

GPβ rs1654498 G A 0443 994 0 158 0000 0583 0000 0863 0986 0158

GPβ NT_01110915_27807178 G C 0035 992 0675 0003 0270 0008 0170 0187 0170

GP6 rs10418743 T C 0087 994 0331 0002 0171 0015 0264 0450 0 171

GP6 NT_01110915_27794008 A G 0031 994 0173 0247 0550 0 154 0940 0619 0 173

GPβ rs1654495 G T 0457 994 0184 0000 0574 0000 0997 0821 0184

GP6 rs1671152 A C 0 168 990 0187 0000 0236 0000 0269 04Θ8 0187

GPβ rs1β71214 T C 0309 994 0189 0000 0688 0000 0669 0587 0 189

GP6 rs12609974 C T 0302 994 0 -98 0000 0746 0000 0191 0267 0191

GP6 rs118802SS A G 0070 994 0206 0997 0904 0724 0363 0832 0206

GP6 rs4029 G A 0118 992 0970 0001 0455 0003 0310 0300 0300

GP6 rs1671176 T G 0265 994 0331 0000 0736 0000 0471 0838 0331

GP6 rs11669150 G A 0205 994 0897 0000 0737 0000 0345 0390 0345

GP6 rs17836526 A T 0024 994 0640 0011 0756 0038 0345 0470 0345

GP6 G A 0343 986 0401 0000 0987 0001 0745 0849 0401

GPβ rs703467 T C 0256 994 0577 0000 0907 0002 0450 0541 0450

GP6 A G 0139 994 0465 0016 0846 0039 0840 0890 0465

GPβ NT_01110915_27864368 O G 0000 994

GRAP2 NT.011520 10J9755906 A C 0020 994 0506 0940 0735 0976 0383 0612 0383

GRAP2 NT_011520 10_19757762 A G 0005 994 0871 0726 0471 0363 0639 0746 0471

GRAP2 NT_O1152010_19746761 C T 0001 994 0611 0533 0637 0332 0921 0516 0516

GRAP2 rs138011 A G 0 187 994 0522 0650 0863 0768 0683 0756 0522

GRAP2 rs9611236 O G 0000 994

GRB2 NT_010641 1S_7243152 G C 0064 994 0536 0098 0572 0077 0056 0058 0056

GRB2 [512600908 T C 0099 990 0687 0245 0702 0120 0664 0318 0318

GRB2 rs8079197 C G 0216 994 0744 0954 0462 0809 0594 0866 0462 GRP58 NT_010194 16J4852141 G A 0017 994 0670 0594 0053 0919 0483 0836 0053

GRPS8 NT_01019416_14834350 G C 0079 994 0843 0467 0604 0261 0142 0082 0082

G RP 58 NT_O1O1Θ4 16J4854368 C T 0009 994 0280 0435 0157 0357 0189 0.205 0 157

GRP58 NT-OIOI 3416J4853136 T C 0016 994 0997 0942 0225 0874 0379 0589 0225

GRP58 πs8040336 G A 0450 994 0765 0145 0428 0102 0763 0.475 0426

GRP58 ra2411284 C T 0.285 994 0832 0532 0650 0414 0898 0645 0645

GRP58 NT_010194 1β_14844259 O A 0.000 994

GTF2A2 rs1O57058 T C 0050 994 0011 0773 0132 0526 0832 0774 0011

GTF2A2 rs71804OB A T 0328 994 0236 0113 0014 0051 0227 0106 0.014

GTF2A2 rs11829842 A T 0265 994 0118 0210 0025 0155 0375 0285 0025

GTF2A2 rs12910751 C T 0322 994 0231 0148 0027 0071 0415 0195 0027

GTF2A2 rs8O41223 C G 0353 972 0316 0203 0 111 0055 0 146 0038 003B

GTF2Λ2 rs15S2031 C T 0326 994 0374 0133 0050 0057 0357 0155 0050

GTF2A2 rs1979422 T C 0366 994 0.269 0074 0063 0079 0.253 0.240 0.063

GTF2A2 rsS151562 T C 0043 988 0349 0937 0220 0609 0533 0345 0220

GTF2A2 rsβ494124 C T 0306 994 0405 0547 0235 0297 0477 0524 0235

GTF2A2 ra17236804 A G 0222 994 0.287 0052 0570 0070 0595 0548 0287

GTF2A2 rιs6151554 C T 0004 994 0347 0335 0398 0718 0521 0989 0347

GTF2A2 rs1552032 C T 0264 992 0669 0659 0650 0915 0724 0412 0412

GTF2Λ2 rs11071467 G A 0193 994 0510 0519 0773 0690 0891 0965 0510

GTF2A2 rs1802671 O G 0000 994

ILK NT.00923717_5418541 A G 0017 994 0465 0915 0029 0714 0747 0786 0029

ILK rs104339O A G 0259 994 0259 0466 0032 0423 0351 0340 0032

ILK C T 0488 994 0104 0979 0036 0740 0911 0753 0036

ILK rs2S55iao T C 0251 994 0373 0.225 0832 0428 0138 0358 0138

ILK rs2292195 T C 0254 994 0456 0446 0789 0673 0286 0553 0286

INSR rsS510959 T C 0165 994 0480 0492 0317 0707 0009 0081 0009

INSR rs286O177 G T 0243 994 0162 0545 0018 0569 0016 0064 0016

INSR NT_01125514_70β4975 G A 0002 994 0367 0084 0776 0098 0022 0041 0022

INSR rs16994192 T C 0004 994 0032 0510 0242 0 S05 0988 0.910 0032

INSR NT_01125514_7055197 G C 0002 994 0049 0597 0904 0579 0107 0 S98 0049

INSR rs2059807 A G 0390 994 0331 0486 0536 0625 0050 0.171 0050

INSR rs891O87 T C 0072 994 0601 0166 0539 0495 0057 0370 0057

INSR rs11883325 T C 0232 994 0274 0 195 0253 0139 0186 0124 0 124

INSR rs2245β55 G T 0064 988 0764 0409 0722 0788 0136 0509 0 136

INSR NT_011255 14_7072173 G C 0002 994 0549 0419 0219 0271 0734 0448 0219

INSR rs2245649 C T 0066 994 0777 0508 0419 0980 0220 0739 0220

INSR rs891088 C T 0247 994 0645 0869 0258 0972 0239 0309 0239

INSR NT_01125514_7107867 T C 0016 994 0252 0863 0788 0836 0988 0938 0252

INSR NT_011255 14_7112756 A G 0168 994 0418 0682 0796 0981 0263 0625 0263

INSR rs1051690 A G 0158 994 0357 0246 0598 0293 0588 0596 0357

INSR rs1799815 A G 0073 994 0675 0917 0442 0974 0373 0534 0373

INSR NT_011255 14.7065616 G C 0009 994 0382 0 789 0967 0975 0623 0501 0382

INSR NT_011255 14_7062799 A G 0011 994 0425 0895 0409 0859 0728 0841 0409

INSR rs2252673 C G 0153 994 0561 0987 0942 0247 0444 0429 0429

INSR rs2860175 T C 0 107 994 0457 0926 0545 0546 0493 0932 0457

INSR rs3745550 A G 0186 994 0565 0960 0583 0740 0724 0858 0565

INSR NT_01125S 14_7055453 0 G 0000 994

INSR NT_01125514_7057083 O G 0000 994

INSR NT_011255 14_7062669 0 C 0000 994

INSR NT_011255 14_7062903 O C 0000 992

INSR NT 011255 14 7066638 O G 0000 994 INSR NT.0112SS 14_7072333 O G 0000 994

INSR NT_O1125S 14_7081S05 O C 0000 994

INSR MT_O112S514_7090491 O G 0000 994

INSR NT_O1125S 14_7112413 O G 0000 994

IRS1 re16822573 T G 0041 994 0359 0528 0279 0217 0191 0077 0077

IRS1 rs1801276 C G 0023 994 0284 0887 0153 0371 0979 03S4 0 153

IRS1 rs3731597 A G 0015 994 0982 0995 0494 0570 0744 0691 0494

IRS1 NT.OO54O314_77870415 C G 0017 994 0914 0782 0552 0789 0915 0511 0.511

IRS1 re1801278 A G 0068 994 0790 0-289 0872 0373 0604 0704 0604

ΓTGAΣ NTJM671314_2870077 G A 0030 994 0672 0717 0001 0461 0538 0491 0001

ITGA2 rs6450105 C T 0030 994 0672 0717 0001 0461 0538 0491 0001

ITGA2 rs2464O6 G A 03S9 994 0002 0502 0407 0710 0508 0590 0002

ITGA2 NT_00671314_3021075 T C 0028 994 0696 0119 0167 0048 0015 0009 0009

ITGA2 rs3212418 G A 0458 994 0013 0699 0247 0926 0617 0952 0013

FTGA2 rs16880B75 G A 0030 994 0949 0168 0382 0479 0019 0201 0019

ITGA2 rs3212632 C T 0080 994 0990 0169 0221 0487 0019 0209 0019

ITGA2 NTJX6431 13_2909230 C T 0001 994 0563 0397 0192 0098 0109 0020 0020 rTGA2 rs3212636 G A 0002 994 0391 0782 0661 0314 0088 0024 0024

ITGA2 «3212603 T C 0.232 994 0236 0377 0025 0046 0683 0067 0.025

ITGA2 rs12515434 T C 0096 994 0708 0229 0241 0637 0025 0274 0025

ITGA2 rs321239l T A 0454 994 0026 0472 0316 0275 0480 02(31 0026

ITGA2 «35236 T G 0160 994 0027 0874 0062 0892 0806 0836 0027

ITGA2 ra770S328 T C 0193 994 0513 0761 0034 0330 0633 0229 0034

ITGA2 rs1688O63β T C 0175 994 0536 0100 0580 0029 0123 0036 0036

ITGA2 rs266β1 C T 0341 994 0313 0315 0037 0037 0860 0177 0037 rτGA2 rs26679 G C 0338 994 0290 0397 0038 0053 0749 0.220 0038

ITGA2 rs33446 C G 0355 994 0402 0516 0039 0063 0675 0211 0039

ITGA2 re17294112 C T 0029 994 0081 0360 0231 0843 0041 0400 0041

ITGA2 NT_00671314_2880224 A C 0002 994 0962 0369 0041 0163 0603 0255 0041

ITGA2 rs3212682 G A 0032 994 0O43 0958 0618 0251 0991 0224 0043

ITGA2 NT_00671314_2849678 T C 0103 994 0053 0955 0436 0747 0943 0746 0053

ITGA2 rs3212429 C T 0048 994 0158 0938 0057 0921 0773 0826 0057

ITGA2 rs1062S35 A G 0398 994 0058 0497 0680 0939 0219 0697 0058

ITGA2 rs1445942 C T 0264 994 0366 0335 0 111 0048 0526 0058 0058

1TGA2 rs3212602 T C 0036 994 0328 0138 0363 0074 0099 0058 0058

ITGA2 rs1O061730 A G 0 185 994 0517 0206 0066 0036 0347 0060 0060

ITGA2 NT_006713 14_2955520 T G 0003 992 0061 0200 0432 0246 0638 0609 0 D61

1TGA2 TS1S3141 C T 0410 994 0063 0688 0390 0539 0723 0902 0 063

UGA2 rs989073 A C 0334 994 0064 0517 0827 0972 02B9 0795 0064

ITGA2 rs1126643 T C 0401 994 0065 0482 0753 0970 0207 0731 0065

UGA2 rs10O52267 G A 0 133 994 0946 0258 0253 0048 0352 0065 0065

ITGA2 rs11741738 C T 0326 994 0 125 0470 0072 0 130 0818 0340 0072

ITGA2 rs3212417 G A 0 17B 994 0403 0925 0 117 0 153 0728 0072 0 Q72

ITGA2 TS3212472 T A 0326 938 0073 0386 0480 0964 02S5 0934 0073

ITGA2 rs3756532 A G 0456 994 0663 0576 0527 0865 0073 0345 0 073

ITGA2 rs3212531 C G 0079 994 0085 0721 0616 0828 0962 0983 0085

ITGA2 G A 0472 994 00B7 0616 0258 0703 0 181 0341 0087

ITGA2 rs716436 T C 0317 994 0087 0952 0139 0404 0378 0673 0087

ITGA2 NT_006713 14_2879457 A C 0066 994 0586 0429 0671 0808 0095 0459 0095

ITGA2 rs2233216 G A 0038 994 0590 0280 0757 0139 0 192 0096 0 096

ITGA2 rs3212386 T C 0 155 994 0378 0132 0639 0060 0202 0096 0096

ITGA2 rs3212641 A G 0160 994 0265 0275 0430 0645 0 101 0450 0101 fTGA2 rs2068247 T C 0403 0442 0953 0171 0566 0105 0633 0105

FTGA2 rs1421929 C T 0486 992 0111 0530 0244 0623 0245 0411 0111

ITGA2 rs32124β7 A G 0307 994 0113 0593 0.551 0762 0409 0844 0113 rTGA2 NT_Q0671314.2932342 A G 0006 S94 0928 0825 αsoo 0762 0117 0172 0117

ITGA2 rs4865755 G A 0197 994 0584 0349 0.406 0018 0685 0 122 0122 fTGA2 ra152088 T C 0196 994 0324 0907 0 125 0719 0930 0.616 0.125

ITGA2 IS17298242 A G 0.255 0686 0428 0217 0087 072S 0125 0125

ITGA2 ra26682 G T 0448 994 0126 0319 0970 0.166 0510 0.275 0126 rrβA2 rs119S58B0 T C 0319 994 0127 0957 0425 0105 0326 0364 0127

IT6A2 rs3212657 C T 0121 994 0128 0919 0448 0795 0.963 0845 0128

ITGA2 «3212574 T C 0-208 994 0733 0S10 0871 0237 0305 0132 0132 rTGA2 NT.006431 13_293SS6β G A 0005 994 0297 0423 0137 0348 0920 0666 0137 rs6B95049 A C 0449 994 0138 0418 0893 0262 0641 0413 0138

ITGA2 rs3212383 A G 0194 0286 0374 0466 0018 0565 0138 0138

UGA2 re17298473 G A 0325 994 0725 0746 0.141 0130 0239 0735 0 141

(TGA2 N(T_00671314_2870194 A T 0194 0402 0379 0472 0018 0537 0141 0141

ITGA2 rs3212S02 A G 0112 994 0495 0897 0 153 0424 0525 0725 0153

ITGA2 NT_006713 14_2952360 T A 0003 994 0875 0919 0 158 0540 0362 0 184 0158

ITGA2 rs3212483 T C 0297 0315 0557 0 173 0 104 0974 0 160 0160

1TGA2 rs12520747 G C 0322 994 0771 0607 0 170 0068 0711 0 164 0164

ITGA2 rs1316250 G 0296 0.170 0815 0335 0532 0623 0589 0170

ITGA2 rs6B593S5 T C 0401 994 0794 0593 0283 0882 0172 0523 0 172

ITGA2 rs7725246 G T 0379 994 0 175 0388 0519 0958 0236 0883 0 175

ITGA2 rs3212430 A G 0347 994 0756 0384 0614 0081 0923 0 185 0185 fTGA2 NT_α0671314.2915721 T C 0021 994 0744 0530 0S86 0246 0486 0 189 0 189

ITGA2 rs278S0 G A 0073 0 198 0728 0578 0896 0900 0559 0198

ITGA2 rs35233 T 0 142 994 0953 0947 0210 0568 0888 0492 0210 tTGA2 rs3212627 A T 0 177 0673 0577 0776 0262 0517 0211 0211

ITGA2 rs773S277 A G 0214 994 0219 0718 0661 0069 0402 0246 0219

ΓΓGA2 G C 0455 994 0222 0369 0865 0618 0233 0549 0222 tTGA2 rs990602 G A 0455 994 0222 0369 0865 0618 0233 0549 0222

ITGA2 G 0 198 994 0239 0516 0791 0250 0523 0245 0239

ITGA2 rs7719848 A G 0282 994 0581 0888 0244 0207 0482 0259 0244

ITGA2 rs3212543 C T 0080 994 0578 0977 0273 0414 0920 0352 0273

ITGA2 rs16880892 A G 0098 994 0517 0658 0309 0226 0785 0274 0274

ITGA2 rs3212433 G 0379 0285 0554 0503 0253 0996 0394 0285

ITGA2 rs30001 G 0 189 994 0309 0747 0829 0877 0759 0472 0309

ITGA2 rs10054234 C 0 169 994 0381 0743 0926 0937 0362 0678 0362

ITGA2 rs1421934 T C 0 109 994 0564 0631 0367 0780 0755 0570 0367

ITGA2 rs58948S4 T C 0293 S88 0373 0402 0545 0456 0499 0579 0373

ITGA2 T G 0100 0458 0702 0408 0631 0787 0471 O 408

ITGA2 T 0303 992 0547 0395 0529 0512 0417 0587 0417

ITGA2 rs3212695 A C 0001 994 0861 0177 0894 0 342 0430 0684 0430

ITGA2 rs321269O G A 0011 0457 0865 0546 0448 0972 0505 0457

ITGA2 rs3212681 A G 0178 994 0937 0672 0536 0 166 0470 0482 0470

ITGA2 rs11742558 T C 0345 994 0699 0383 0713 0315 0 S87 0478 047B

ITGA2 rs246410 G A 0345 0699 0383 0713 0315 0587 0478 0478

ITGA2 rs988S74 C 0023 994 0570 0770 0478 0795 0935 0985 0478

ITGA2 NT_0D6713 14_2870521 C T 0003 994 0967 0661 0992 0937 0893 0509 0509

ITGA2 rs3212661 T 0065 0671 0836 0527 0830 0876 0951 0527

ITGA2 rs121529S4 A G 0003 994 0643 0649 0785 0941 0957 0 533 0533

ITGA2 NT 006713 14 2873793 A 0001 0542 0582 0552 0836 0955 0828 0542 ITGA2 rs30094 T C 0105 994 0731 0514 0554 0.S36 0677 0797 0.554

ITGA2 NT.00671314_2β88121 G T 0003 994 0597 0379 0944 0364 0807 0956 0597

ITGA2 rs3212684 T C 0063 994 0982 0719 0899 0504 0624 0940 0624

ΓΓGA2 rs3212699 A G 0042 994 0782 0 B74 0693 0622 0851 0762 0693

ITGA2 NT_00671314.2830237 O C 0000 S94

ITGA2 NT_006713 14_2837S37 O G 0000 994 rTGA2 re321266O O A 0.000 994

ITGA2 rs35237 O C 0000 930

ΓTGA2 NT_00671314_2946197 O G 0000 994

ITGA2 rs3212685 O T 0000 994 rτGA2 rs3212691 O A 0000 994

1TGA2 NT_00β7iai4_29654O6 O T 0000 994

ITGA2 TS3212644 O A 0000 994

ITGA2B rs5910 T C 0382 994 0.297 0554 0224 0763 0707 0224 0224 rTGA2B fs8SO73O G C 0385 990 0339 0553 0274 0779 0685 0227 0227

(TGB1 rs11009131 T G 0018 994 0.279 0854 0021 0705 0533 0295 0021

ITGB1 rs2488311 T C 0487 994 0321 0517 0049 0563 0167 0273 0049

1TGB1 NT.008705 15_152242B9 T C 0016 992 0553 0867 0067 0297 0810 0246 0067

ITGB1 rs24βS320 T C 0426 978 0639 0539 0067 0426 0113 0131 0067

ΓΓGBI re16933819 G A 0156 994 0796 0.247 0671 0182 0072 0083 0072

1TGB1 rs155715O G A 0284 992 0637 0424 0158 0240 0131 0035 0085

ΓTGBI rs16933842 G A 0098 994 0087 0341 0615 0735 0482 0990 0087

ITGB1 rs2SO399S GG C 0489 994 0382 0447 0087 0488 0179 0276 0087

ITGB1 rs7914799 TT A 0267 994 0552 0279 0327 0204 0119 0118 0118

ITGB1 rs2457706 TT A 0204 994 0142 0319 0443 0650 0393 0793 0142

ITGB1 re12248136 CC G 0093 994 0158 0270 0539 0497 0532 0858 0158

ITGB1 rs1187056 AA G 0443 994 0263 0392 0426 0564 0163 0362 0 163

ITGB1 rs2503997 TT C 0316 994 0960 0604 0372 0366 0278 0 167 0167

ITGB1 TS224SS44 GG T 0496 994 0481 0481 0247 0723 0181 0.451 0 181

ITGB1 rs2503995 CC G 0389 994 0922 0637 0267 0581 0184 0235 0 184

ITGB1 rs1187078 G A 0456 956 0842 0415 0402 0388 0200 0246 0200

ITGB1 rs248β330 G C 0184 984 0569 0552 0206 0725 0951 0798 0206

ITGB1 rs24S8335 G C 0346 994 0345 0542 0476 0986 0214 0680 0214

ITGB1 rs1187095 G A 0072 992 0684 0498 0222 0611 0968 0222 0222

ΓΓGBI rs1187101 T C 0491 994 0681 0578 0801 0829 0234 0534 0.234

ITGB1 rs1187093 C G 0469 994 0796 0423 0690 0547 0272 0438 0272

ITGB1 re1187097 T C 0453 994 0894 0470 0968 0599 0275 0445 0275

ITGB1 rs17296289 A G 0067 994 0918 0608 0448 0226 0831 0290 0290

ITGB1 rs11595981 A G 0091 994 0302 0823 0754 0783 0943 0649 0302

ITGB1 rs12266969 0092 994 0306 0834 0840 0714 0994 0548 0306

ITGB1 TS2475193 0251 994 0314 0443 0672 0627 0981 0889 0314

ITGB1 rs1187069 0482 994 0635 0678 0372 0804 0316 0528 0316

1TGB1 rs1009002 G A 0476 994 0912 0561 0796 0918 0338 0779 0338

ITGB1 rs2488336 A G 0412 994 0793 0763 0774 0821 0344 0501 0344

ITGB1 rs10827150 C T 0089 992 0969 0513 0611 0981 0345 0962 0345

ITGB1 rs2153875 C A 0251 994 0684 0808 0346 0612 0954 0722 0346

IT6B1 re11009157 A G 0244 992 0891 0668 0915 0902 0396 0763 0396

ITGB1 rs11009125 G A 0106 992 0486 0728 0468 0443 0840 0516 0468

ITGB1 NT_008705 15_15184355 A G 0025 994 0494 0708 0598 0934 0630 0893 0494

ITGB1 rs722432 A G 0074 994 0591 0997 0584 0410 0732 0496 0496

ITGB1 rs16933771 G A 0052 994 0789 0416 0778 0834 0497 0952 0497

ITGB1 rs2488326 T C 0107 994 0666 0969 0497 0917 0975 0906 0497 ITGB1 NT.00870515JI5246220 G A 0024 992 0628 0797 0896 0420 0895 0529 0529

ITGB1 rs2504004 G A 0 159 994 0605 0423 0670 0485 0545 0685 0545

ITGB1 NTJJ0870S 1S_15224208 A G 0172 994 0935 0984 0634 0891 0637 0547 0547

ITGB1 «10827164 G A 0349 994 0553 0771 0754 0520 0929 0570 0553

ITGB1 rs2974542 C G 0296 994 0723 0872 0745 0994 0725 0871 0723

ITGB1 NT_00870S 15_1S194239 O T 994

ITGB3 A G 0 153 994 0923 0226 0947 0080 0036 0013 0013

ITGB3 rsi 1079764 T C 0422 994 0538 0133 0972 0074 0029 0019 0.019

ITGB3 IS12603843 T C 0413 994 0269 0189 0 138 0008 0822 0033 0033

ITGB3 NT_01078314_4041487 T C 0061 994 0397 0985 0.434 0257 0398 0039 0039

ITGB3 r-2292887 A G 0105 994 0039 0362 0235 0423 0083 0166 0039

ITGB3 NT.010783 14_4016824 A C 0097 982 0040 0242 0319 0278 0052 0103 0040

ITGB3 rsS895150 C T 0391 994 0263 0154 0177 0061 0181 0066 0065

ITGB3 rs16941731 C T 0131 994 0853 0.219 0697 0 175 0079 0081 0079

ITGB3 rs3892084 A G 0155 994 0084 0324 0483 0526 0 167 0402 0084

1TGB3 nil 6941768 C T 0043 994 0884 0202 0693 0505 0086 037Θ 0086 rTGB3 rs12603582 T G 0213 994 0095 0.718 0092 0807 0351 0494 0092

ITGB3 re17605348 G A 0.097 992 0857 0070 0865 0083 0.097 0124 0097

ITGB3 ra11867160 G A 0057 976 0 101 0590 0.245 0498 0931 0739 0101

ITGB3 rs11079770 C G 0 159 994 0 102 0338 0726 0658 0240 0 B17 0102

UGB3 rs16941702 A G 0047 994 0 116 0598 0593 0855 0442 0190 0 116 rTGB3 ra2292866 G A 0122 894 0.207 0352 0815 O 290 0143 0142 0142

ITGB3 NT_01078314_4021526 A G 0017 994 0493 0330 0573 0584 0142 0395 0142

(TGB3 rs7216112 A G 0353 994 0 145 0.257 0396 0350 0362 0 S12 0145

ITGB3 re3783870 G A 0007 994 0160 0895 0189 0 S47 0850 0649 0160

ITGB3 rs116S0072 A G 0383 992 0407 0078 0644 0 145 0172 0309 0172

ITGB3 rs12709458 G T 0183 994 0197 0348 0914 0585 0308 0603 0 197

FTGB3 rs3851806 C G 0156 992 0203 0982 0724 0657 0516 0326 0203

ITGB3 rs722S575 C T 0324 994 0211 0516 0726 0615 0917 0993 0211 rTGB3 rs7217214 G A 0208 994 0580 0004 0921 0039 0224 0631 0224

ITGB3 ra11868894 G A 0 173 994 0243 0318 0997 0400 0226 0344 0226

[TGB3 rs37444S3 C T 0041 S94 0859 0072 O 705 0416 0230 0850 0230

ITGB3 rs8078β14 A G 0218 994 0779 0005 0739 0038 0241 0580 0241

ITGB3 rs11652772 G A 0282 994 0345 0171 0953 0348 0248 0517 0248 rTGB3 rs5919 C T 0061 S94 0676 0774 0615 0586 0756 0.249 0.249

ITGB3 1-7220842 A C 0262 994 0994 0063 0734 0 116 0255 0393 0255

ITGB3 rs11655536 G A 0273 994 0787 0749 0993 0668 0705 0260 0260

ITGB3 rs8077375 T C 0 170 994 0319 0014 0824 0051 0277 0515 0277

ITGB3 re5918 G A 0186 914 0495 0015 0977 0058 0327 0613 0327

ITGB3 rs7217710 G A 0314 994 0481 0047 0377 O 205 0994 0619 0377

ITGB3 G C 0307 994 0637 0049 0505 0242 09S8 0564 0505

ITGB3 rs2056131 A G 0332 994 0861 0207 0713 0550 0946 0508 0508

ITGB3 rs16941829 A G 0053 994 0771 0531 0572 0996 0963 0509 0509

ITGB3 ra15908 G T 0368 994 0520 0077 0678 0169 0858 0976 0520

ITGB3 rs4θ2S024 G A 0326 994 0547 0 196 0679 0308 0911 0827 0547

ITGB3 rs4S25555 A G 0325 994 0583 0197 0717 0317 0921 0823 0 S83

ITGB3 TS3760372 A G 0347 994 0679 0375 0791 0367 0613 0583 0583

ITGB3 1652097 T C 0390 994 0833 0450 0673 0659 0711 0587 0587

ITGB3 rs2015729 T C 0391 994 0619 0094 0999 0 197 0813 0986 0619

ITGB3 rs3809863 A G 0458 994 0827 0373 0944 0389 0728 0697 0697

ITGB3 rs8066295 A G 0 294 994 0940 0135 0854 0361 0901 0706 0706

ITGB3 rs7209700 G A 0 334 994 0874 0059 0988 0249 0795 0717 0717 ITGB3 rs10514919 T G 0269 994 0953 0117 0916 0305 0940 0723 0723

ITGB3 rs11658221 T G 0269 994 0953 0117 0916 0305 0940 0723 0723

ITGB3 rs5921 Q G 0000 994

ITPRI NT.02251717_46920O1 A G 0.001 994 0039 0.248 0002 0099 02BO 0109 0002

ITPR1 rs17788144 C T 0125 994 0003 0415 0003 0463 0198 0309 0003

ITPR1 NT_022517 16_4749969 C T 0423 994 0003 0506 0.023 0342 0367 0257 0003

ITPR1 NT_022517 16_4708604 T C 0055 994 0010 0243 0320 0789 0622 0683 0010

ΓTPRI rs4684443 A G 0258 994 0014 0648 0757 0621 0540 0576 0014

ITPR1 NT_02251716.4761019 A G 0149 994 0024 0064 0016 0073 0118 0149 0016

ITPR1 NT_02251717_4748477 T C 0010 994 0 137 0456 0027 0473 0476 0493 0027

ITPR1 rs6442895 C G 0166 994 0029 0204 0404 0301 0460 0583 0029

ITPRI rs931139S T C 0408 994 0034 0341 0.411 0504 0592 0776 0034

ITPRI NT.022517 16_4688193 A G 0194 994 0036 0740 0878 0959 0585 0.434 0036

ITPR1 rs7652028 G A 0196 994 0039 0639 0915 0939 0557 0417 0039

ITPR1 rs13316843 A G 0163 994 0040 0874 0988 0817 0971 0702 0040

ITPR1 rs6442896 T G 0162 994 0049 0397 0S58 0539 0724 0854 004S

ITPR1 rs901856 A G 0117 994 0962 0 162 0881 0338 0050 0207 0050

ITPR1 rs23O6877 G T 0173 994 0405 0653 0062 0729 0506 0765 0062

ITPR1 rs11920001 G A O 1S9 994 0 101 0627 0969 0337 0 105 0064 0064

ITPR1 rs2633722 G T 0139 994 0472 0344 0073 0977 0204 0917 0073

ITPR1 rs23O6875 G A 0325 994 0223 0904 0075 0656 0720 0720 0075

ITPRI (S2306879 G A 0320 994 0259 0998 0075 0806 0666 0898 0075

ITPR1 πs3816835 T G 0434 994 0091 0517 0563 0773 0979 0799 0091

ITPR1 rs7613447 A G 0162 994 0136 0691 0901 0059 0573 0158 0136 rrpRi rs1036839 A C 0381 994 0641 0 196 0138 0120 0600 0362 0138

ITPR1 rs3792487 A G 0328 992 0274 0891 0148 0684 0740 0734 0148

ITPRI rs3796336 G T 0240 994 0 149 0.747 0950 0964 0971 0708 0149

ITPR1 rs733018 G T 0232 994 0 153 0832 0745 0985 0324 0363 0153

ITPR1 NT_O22S17 17_4656708 T C 0019 994 0 157 0290 0754 0685 0392 0926 0157

ITPR1 NT_022517 16_4627653 G T 0154 994 0159 0264 0927 0425 0919 0811 0 159

ITPR1 rs9866640 G A 0177 994 0591 0186 0612 0419 0 176 0497 0 176

ITPR1 NT.022517 16_4818743 A G 0204 994 0761 0465 0720 0 189 0487 0177 0177

ITPR1 NT_022S17 17_4828756 A G 0047 994 0178 0971 0497 0892 0955 0829 0178

ITPR1 IS68O1563 G A 0303 994 0 178 0041 0436 0094 0 185 0317 0178

ITPR1 rs931389 A G 0452 994 0219 0261 0598 0549 0684 0926 0219

ITPR1 π>6793265 T C 0132 994 0389 0462 0512 0485 0252 0338 0252

ITPR1 rs64429O5 A G 0021 994 0264 0457 0723 0529 0306 0422 0264

ITPR1 NT_022517 16_4654841 T C 0007 994 0309 0733 0280 0856 0741 0708 0280

ITPR1 rs68O1737 T A 0 126 994 0848 0 Θ43 0284 0750 0736 0782 0284

ITPR 1 G C 0 132 994 0592 0064 0593 0052 0433 0288 0288

ITPR1 rsB73135 G T 0480 994 0296 0885 0355 0784 0516 0494 0296

ITPR1 NT_022517 16_466S555 C G 0045 994 0573 0503 0310 0420 0 864 0874 0310

ITPR1 NT.022517 17_4828552 T A 0049 990 0310 0964 0701 0951 0 918 0934 0310

ITPR1 NT.022517 16_4654920 G A 0012 994 0459 0327 0332 0357 0582 0611 0332

ITPRI rs23O68β1 C T 0494 994 0337 0510 0874 0599 0580 0681 0337

1TPR1 NT_022517 16_4644816 T C 0006 994 0523 0911 0698 0824 0338 0547 0338

ITPR1 TS3792490 A G 0289 992 0339 0944 0414 0885 0989 0814 0339

ITPR1 NT_022517 16_4782275 T C 0001 994 0528 0494 0542 0249 0793 0363 0363

ITPR1 NT.022S17 16_4498O1S C T 0 161 994 0821 0847 0619 0437 0825 0387 0387

ITPR1 rs304076 A C 0348 994 0850 0195 0395 0145 0793 0562 0395

ΓΓPRI rs9823748 T C 0489 994 0506 0455 0943 0663 0408 0674 0408

ITPR1 rs38O4984 C T 0331 994 0863 0395 0828 0689 0412 0785 0412 ITPR1 rs304074 T C 0317 994 0825 0535 0438 0245 0.993 0497 0438

ITPR1 151994500 G A 0402 994 0895 0616 0439 0863 0728 0992 0439

ΓTPRI πs2291861 C A 0419 992 0671 0490 0462 0695 0867 0942 0462

ITPR1 rs9O1854 C T 0.404 994 0831 0541 0997 0941 1 000 0492 0492

ITPR1 NT_022517 1Θ_4644668 T C 0004 994 0898 0754 0589 0841 0543 0681 0543

1TPR1 rs2304820 G A 0232 992 0988 0844 0590 0563 0885 0702 0590 rrPRi rs762S003 T G 0032 968 0746 0946 0840 0989 0681 0723 0681

ITPR1 NT_022S171β_4644906 O C 0000 994

ITPR1 NT_02251717_470821S O C 0000 992

ΓΓPRI NT.022S171β_4787739 O T 0000 994

ITPR1 NT.022S17 17_4827765 O A 0000 994

JAK2 rs10429491 T C 0304 994 0084 0574 0.001 0894 0659 0986 0001

JAK2 NT_∞B413 16_5116343 T C 0005 994 0763 0291 0052 0571 0901 0808 0052

JAK2 rs7034S3θ G A 0222 992 0677 0851 0061 0891 0299 0692 0061

JAK2 NT_0084131β_5117180 G A 0004 994 0709 0612 0980 0457 0073 0.088 0073

JAK2 re10974955 A G 0221 994 0778 0739 0128 0923 0345 0819 0128

JΛK2 NT_0084131β_5116913 A G 0005 994 0554 0315 0142 0.207 0452 0.280 0 142

JAK2 rs2274471 C T 0263 994 0650 0600 0801 0.864 0174 0515 0 174

JAK2 rs7869668 T C 0472 994 0400 0989 0302 0946 0312 0441 0302

JAK2 NT_008413,16_5O40798 A G 0001 994 0976 0603 0725 0884 0871 0413 0413

JAK2 NT_0084131β_5O7O16S O T 0000 994

LAT rs1βO2141 G A 0.015 994 0798 0339 0042 0034 0097 0006 0006

LAT NT_01039315_20310349 C T 0010 994 0800 0503 0205 0 123 0 197 0035 0035

LAT rs992S068 T G 0305 994 0633 0709 0992 0775 0553 0679 0553

LAT rs4788115 A T 0171 994 0945 0857 0966 0861 0832 0890 0832

LAT NT_02481210_398781 O C 0000 994

LAT NT_01039315_20314727 O A 0000 994

LCK rs1042546 G A 0076 994 0029 0535 0073 0559 0864 0839 0029

LCK NT_004511 17_2717559 G C 0001 994 0202 0663 0 165 0516 0 272 0246 0165

LCK NT_0D4511 17_2713551 0 C 0000 994

LCP2 NT_02313312_14507455 A G 0500 994 0246 0090 0017 0534 0 190 0931 0017

LCP2 NT.02313311J4507463 A G 0486 994 0213 0086 0029 0431 0213 0834 0029

LCP2 NT_02313312_14511832 G T 0444 994 0192 0022 0569 0180 0041 0375 0041

LCP2 NT_02313312_I4489697 G C 0023 994 0296 0830 0188 0319 0305 0083 0083

LCP2 NT_02313312_14494972 C A 0457 994 0588 0845 0238 0858 0684 0961 0238

LCP2 NTJJ2313312_14534098 G C 0258 994 0883 0623 0319 0261 0923 0382 0319

LCP2 NT_023133 11_14512002 T C 0065 994 0796 0 137 0485 0287 0330 0600 0330

LCP2 NT_02313312_14495114 T C 0473 994 0696 0562 0332 0839 0496 0824 0332

LCP2 NT_023133 12_14497B31 A G 0028 994 0390 0160 0758 0558 0372 0985 0372

LCP2 NT_023133 12_14494589 T C 0477 994 0663 0567 0386 0823 0414 0722 0386

LCP2 NT_023133 11_14499607 T C 0304 994 0633 0065 0546 0650 0414 0536 0414

LCP2 NT_O23133 11_14524603 G A 0297 994 0899 0420 0743 0290 0690 0474 0474

LDLR rs11669576 A G 0044 994 0858 0010 0936 0044 0013 0079 0013

LDLR rs2226671 T C 0 112 994 0017 0 191 0752 0498 0070 0378 0017

LDLR NT_011295 10_2501439 T C 0022 994 0398 0654 0879 0799 0055 0 173 0055

LDLR NT.011295 10_2494137 C T 0029 994 0115 0103 0328 0039 0202 0062 0062

LDLR NT_011295 10_2505132 A G 0001 994 0796 0707 0250 0301 0273 0098 0098

LDLR NT_O1129S 10_2496688 T C 0011 994 0628 0053 0922 0138 0 103 0273 0103

LDLR rs2304182 A G 0072 986 0157 0419 0111 0496 0968 1 000 0 111

LDLR rs1433099 T C 0253 994 0510 0 105 0633 0081 0244 0172 0172

LDLR rs3826810 T C 0052 990 0743 0201 0246 0489 0856 0776 0246

LDLR rs6413504 G A 0476 994 0843 0950 0794 0898 0278 0476 0278 UH-R 154508523 A G 0131 994 0516 0156 0398 0224 0336 0427 0336

LOLR rs5929 A G 0035 994 0430 0106 0881 0428 0345 0938 0345

LDLR rs179989B T C 0113 994 0346 0.997 0784 0527 0743 0626 0346

LDLR rs1003723 T C 0455 994 0420 0632 0514 0713 0784 0876 0420

LDLR re2738465 A O 0323 994 0809 0351 0709 0 168 0882 0532 0532

LDLR IS273&460 T C 0.279 994 0699 0112 0978 0072 1 000 0556 0556

LOLR rs5S2S G A 0433 994 0612 0898 0560 0933 0875 0753 0560

LDLR rs14158 A G 0272 994 0677 0 106 0.862 0070 0952 0591 0591

LYN NT_0081B317_8709069 G A 0266 994 0086 0791 0390 0710 0.380 0379 0086

LYN rs7813271 G A 0183 992 0102 0075 0279 0047 0153 0095 0.095

LYN ra1B922478 G A 0001 994 0787 0171 0655 0427 0 194 0567 0194

LYN rs10100561 C A 0287 994 0337 0.857 0689 0964 0586 0578 0337

LYN re1027987 G A 0432 994 0,367 0264 0761 0290 0786 0743 0367

LYN rs7828258 T C 0477 994 0880 0331 0944 0278 0451 0396 0396

LYN «2668011 T C 0252 994 0559 0782 0837 0762 0795 0819 0559

MADD NT.00923717_46138044 T C 0004 994 0415 0829 0003 0614 0850 0633 0003

MADD rs3738101 A G 0 116 994 0.280 0597 0015 0475 0367 0309 0015

MADD NT_00923717_46132443 A G 0011 994 0046 0074 0045 0224 0342 0726 0045

MADD «2291119 T C 0.297 994 0333 0945 0.491 0559 0 151 0064 0064

MADD rs2290149 G A 0 144 994 0630 0645 0113 0604 0807 0740 0113

MADD NT_00923717_46135S07 T C 0018 980 0145 0709 0266 0924 0621 0946 0145

MADD NT.00923717_4S099108 C G 0001 994 0444 0689 0191 0996 0340 0725 0191

MADD NT_00923717_4β101581 G A 0033 994 0193 0408 0611 0997 0440 0831 0193

MADD rs7943429 C T 0029 994 0450 0828 0310 0962 0295 0267 0267

MADD rs1449626 C A 0176 994 0841 0356 0602 0396 0276 0350 0276

MADD NT.009237 17_46090290 A G 0055 994 0407 0816 0908 0950 0651 0917 0407

MADD rs753993 T G 0202 S94 0630 0418 0410 0534 0632 0763 0410

MADD rs3816725 C A 0236 990 0900 0356 0678 0474 0418 0575 0418

MADD NT.00923717_46082671 O T 0000 994

MADD NT_00923717_4609ai3O O G 0000 994

MADD NT.009237 17_46117441 O G 0000 S94

MAP2K1 rs11637558 C A 0252 986 0034 0517 0005 0273 0403 0.221 0005

MAP2K1 rs1B949939 A G 0024 994 0271 0750 0052 0 194 0691 0 133 0052

MAP2K1 NT.010194 16_37572367 A G 0087 994 0906 0511 0311 0240 0431 0.202 0202

MAP2K1 rs16949924 C G 0355 994 0236 04B1 0367 0835 0512 0974 0236

MAP2K1 NT.01019416_37573046 T C 0002 9S4 0497 0886 0350 0659 0381 0296 0296

MAP2K1 rs2229676 A G 0019 994 0943 0837 0819 0838 0658 0696 0658

MAP2K1 rs17586159 A G 0019 994 0943 0837 0819 0838 0658 0696 0658

MAP2K2 rs35091β A G 0494 994 0222 0988 0001 0638 0283 0176 0001

MAP2K2 NT.01125514_4042449 A G 0.201 994 0748 0979 0375 0338 0361 0072 0072

MAP2K2 fs35O891 A G 0230 994 0949 0517 0124 0735 0793 0248 0124

MAP2K2 rs360890 T C OJ23O 994 0949 0517 0124 0735 0793 0248 0124

MAP2K2 NT_01125514_4040804 T C 0007 994 0332 0716 0439 0702 07B6 0775 0332

MAP2K2 NT.011255 14_4035523 T C 0003 994 0856 0763 0824 0976 0773 0940 0773

MAP2K3 rs3744222 T C 0240 994 0592 D 175 0522 0124 0471 0296 0296

MAP2K3 ra4985837 C T 0235 992 0717 0175 0872 0155 0518 0387 0387

MAP2K3 rs2305874 0 C 0000 994

MAP2K4 NT.01071815_11625033 G A 0008 992 0333 0007 0656 0003 0006 0003 00O3

MAP2K4 rs47922t9 T C 0242 986 0604 0160 0039 0 126 0413 0293 0039

MAP2K4 NT_01071815_11643523 G A 0004 994 0331 0263 0 153 0212 0 113 0 108 0 108

MAP2K5 rs11631474 G A 0476 994 0007 0708 0049 0849 0684 0661 0007

MAP2K5 TS4343227 C T 0 151 994 0011 0463 0 102 0442 0993 0872 0011 MAP2K5 rs37433S3 C T 0097 994 0138 0470 0.369 0439 0454 0423 0138

MAP2K5 rs12592919 T C 0100 994 0209 0514 0.904 0341 0989 0570 0209

MAP2K5 NT_010194 16_^38889762 A G 0036 994 0327 0772 0955 0705 0243 0258 0243

MAP2K5 rs12438118 A C 0.252 994 0975 0329 0706 0629 0507 0.361 0361

MAP2K5 rs2278076 T C 0.223 994 0858 0495 0474 0704 0443 0.404 0404

MAP2K5 NTJ)10194 16_38626097 A G 0001 994 0814 0665 0732 0913 0947 0807 0732

MAP2K6 NTJ)10641 15J440174 T C 0039 994 0020 0439 0991 0303 0159 0119 0020

MAP2K6 NT.010641 15_1443S9< G C 0055 994 0566 0132 0.147 0263 0673 0858 0147

MAP2K6 133815035 C T 0140 994 0780 0551 0233 0817 0391 0718 0.233

MAP2KB re17690945 T C 0 121 994 0775 0529 0432 0801 0289 0^67 0267

MAP2KB rs2O74030 G A 0405 994 0655 0 172 0402 0144 0916 0618 0402

MAP2K6 re11657645 G C 0217 994 0554 0401 0923 0445 0622 0647 0554

MAP2KB rs2074Q28 A G 0377 994 0931 0079 0853 0070 0944 0612 0612

MAPK1 rs13515 T C 0196 994 0238 0021 0647 0009 0138 0053 0053

MAPKI [«2276006 A C 0039 994 0 136 0394 0335 0262 0249 0164 0 136

MAPK1 NTJJ115209_1508798 T C 0032 994 0.143 0772 0200 0569 0651 0206 0 143

MAPKI rs13058 C A 0055 994 0.455 0622 0340 0885 0187 0184 0.184

MAPKI rs381060β C T 0.232 994 0419 0964 0965 0795 0331 0306 0306

MAPK1 ra13943 C G 0473 970 0823 0087 0483 0063 0472 0.384 0364

MAPK1 rs3810609 C T 0473 994 0966 0093 0845 0090 0602 0470 0470

MAPK1 ra3810610 T C 0473 994 0966 0093 0645 0090 0602 0470 0470

MAPK1 rs1063311 A G 0433 994 0908 0086 0745 0151 0659 0713 0659

MAPK1 rs8139376 T G 0435 994 0799 0088 0711 0 159 0699 0730 0699

MAPK1 rs9810271 G A 0387 994 0760 0122 0870 0 147 0906 0938 0760

MAPK11 rs760747 A G 0238 914 0.217 0435 0413 0555 0691 0.787 0217

MAPK14 rs851007 G A 0453 994 0003 0 185 0032 0543 0064 0.425 0003

MAPK14 rs28158O5 C T 0025 994 0007 0554 007f 0999 0151 0594 0007

MAPK14 rs3730385 A G 0019 994 0162 0451 0049 0413 0701 0947 0049

MAPK14 NT_O07592 13_26860641 T A 0026 994 0097 0283 0776 0678 0053 0391 0053

MAPK14 rs373O327 C T 0101 994 0762 0496 0507 0819 0229 0643 0229

MAPK14 FS8510 A G 0076 994 0600 0780 0298 0611 0725 0878 0298

MAPK14 NT_007592 13_26867354 A C 0107 994 0911 0760 0460 0943 0403 0841 0403

MAPK14 rs3804452 A G 0108 994 0749 0705 0768 0803 0660 0835 0660

MAPK14 NT_007592 13_26817588 0 C 0000 994

MAPK14 NT_0O7592 13_26867434 O T 0000 994

MAPK14 NT_00759214_26935615 0 C 0000 994

MPL rs12731981 A G 0033 994 0093 0260 0486 0762 0027 0362 0027

MPL rs16830693 G A 0034 994 0045 0500 0295 0568 0706 0757 0045

MPL rs710252 T C 0396 994 0158 0556 0665 0343 0S88 0360 0158

MPL rs1780670 T C 0396 994 0 158 0556 0665 0343 0 S88 0360 0158

MYLK rs76198S4 C T 0105 992 0693 0552 0552 0190 0158 0049 0049

MYLK rs7641248 G A 0129 994 0263 0240 0393 0136 O 074 0050 0050

MYLK NT_005612.14_30007773 T G 0094 994 0864 0893 0068 0578 0702 0275 0068

MYLK NT_005612 14_29680081 A G 0069 986 0687 0747 0822 0689 0075 0 131 0075

MYLK rs40305 G A 0227 994 0872 0501 0154 0721 0381 0078 0078

MYLK rs6438804 G A 0150 994 0380 0084 0847 0049 0 173 0104 0 104

MYLK A T 0186 978 0765 0 148 0806 0 113 0114 0108 0 108

MYLK rs4678047 C T 0331 994 0881 0370 0416 0195 0298 0143 0143

MYLK rs384591S C T 0143 990 0619 0223 0908 0112 0428 0209 0209

MYLK NTJ305612 14_29B35707 T C 0002 994 0227 0355 0841 0 143 0571 0220 0220

MYLK rs3732487 T G 0016 994 0232 0 139 0293 0199 0298 0406 0232

MYLK rs848145 A G 0054 994 0790 0 318 0761 0 196 0416 0250 0250 MYLK rs820456 T G 0037 994 0300 0176 0808 0211 0262 0326 0262

MYlK NT_00S612 14_2Sβ31235 T C 0001 988 O2S8 0359 0965 0301 0439 0378 02S8

MYLK NT_00S612 14_29947654 T C 0036 994 0361 0354 0662 0965 0596 0588 0361

MYLK NT_0O5612.14_2S898206 T C 0032 994 0700 0 130 0364 0591 0475 0787 0364

MYLK rs17302COβ A G 0107 994 O51S 0443 0390 0481 0423 0459 0390

MYLK NT_00S61214_29947472 G C 0001 934 0.859 0987 0674 0835 0704 0584 0584

MYLK rs270O3S2 A G 0213 992 0586 0358 0971 0.286 0932 0645 0586

MYlK NT_005612 14_29B80363 A G 0026 S94 0923 0726 0600 0.782 0718 0773 0600

MYLK NTJJ0561214_29838834 O C 0000 992

MYLK NT_0056ΪZ14_29896O2O O C 0000

MYLK rs3732485 O G 0000 994

MYLK NT_005612.14_29915470 0 C 0000

MYLK NT_O0S612 14_29951430 o c 0000 994

NFE2L2 re10183914 T C 0362 0027 0812 0052 0837 0631 0.724 0027

NFE2L2 re13005431 G A 0.365 994 0054 0787 0100 0760 0745 0747 0054

NFE2L2 rs1B06649 A G 0255 0155 0777 0088 0575 0568 0425 0088

NFE2L2 rs2444563 G A 0207 994 0606 0038 0841 0289 0100 0641 0100

NFE2L2 rs1962142 A G 009S 994 nm 0580 0650 0796 0109 0335 0109

NFE2L2 rs17647S88 T C 0360 0 115 0935 0 119 0887 0773 0782 0 115

NFE2L2 rs134O1026 T C 0109 994 0144 0451 0.221 0667 0794 0975 0144

NFE2L2 rs13029183 C T 0 109 0144 0451 0221 0667 0794 0975 0144

NFE2L2 rs2247446 A G 0.204 994 0656 0890 0954 0665 0 147 0153 0147

NFE2L2 rs9941681 G A 0208 994 0653 0054 0633 0385 0151 0830 0151

NFE2L2 rs2364722 G A 0325 992 0216 0468 0188 0412 0766 0650 0 188

NFE2L2 132386161 C 0324 986 0217 0516 0 190 0511 0794 0758 0 190

NFE2L2 rs180668S G A 0136 0236 0857 0345 0986 0211 0436 0211

NFE2L2 re12623239 G 0232 994 0771 0075 0948 0288 0217 0638 0217

NFE2L2 «6726395 T 0458 994 0260 0825 0225 0706 0680 0928 0225

NFE2L2 rs10207932 T G 0220 0832 0100 0915 0434 0342 0953 0342

NFE2L2 rs2364725 C 0467 994 0.561 0884 0385 0958 0.516 0665 0385

NFE2L2 rs6433659 T C 0475 0717 0437 0653 0437 0406 0422 0406

NFE2L2 rs12474344 G C 0428 0538 0195 0753 0528 0418 0892 0418

NFE2L2 rs11βBββ84 T A 0425 994 0718 0156 0741 0396 0446 0818 0446

NFE2L2 rs16865105 C A 0221 0547 0455 0751 0461 0449 0482 0449

NFE2L2 rs1349762 T C 0147 994 0457 0772 0845 0774 0877 0839 0457

NFE2L2 re10170546 C T 0280 0608 0420 0618 0711 0471 0845 0471

NFE2L2 rs6433658 C G 0256 994 0782 0198 0766 0.291 0496 0627 0496

NFE2L2 G C 0253 0839 0192 0896 0292 0564 0698 0564

NFE2L2 rs2034678 T A 0204 994 0678 0871 0925 0884 0832 0593 0593

NFE2L2 rs1O497508 C 0119 994 08B6 0634 0906 0992 0605 0937 0605

NFE2L2 rs1453373 G A 0368 0631 0598 0944 0864 0896 0816 0631

NFE2L2 rs2364731 C T 0418 0790 0983 0735 0890 0692 0856 0692

NFE2L2 rs12105484 o c 0000

P2RX1 rs6502752 C G 0237 0388 0022 0079 0017 0 162 0103 0079

P2RX1 NT_010718 15_3403591 T C 0295 994 0784 0239 0703 0 171 0290 0217 0217

P2RY1 rs701265 G A 0 145 0972 0707 0247 0447 0696 0325 0247

P2RX1 rs7219732 T A 0087 0681 0549 0564 0316 0654 0808 0564

P2RY12 rs1472122 A G 0483 994 0001 0111 0066 0482 0063 0491 0001

P2RY12 rs10935839 C T 0355 0003 0032 0583 0355 0050 0635 0003

P2RY12 rs16863323 A G 0279 0067 0489 0029 0404 0425 0387 0029

P2RY12 rs17204437 A G 0181 994 0053 0249 0499 0818 0 151 0773 0053

P2RY12 rs13070270 T C 0209 994 0933 0 198 0670 0041 0315 0055 0055 P2RY12 131388622 T C 0.329 994 0.276 0252 0058 0663 0296 0.425 0058

P2RY12 ra17204376 T G 0087 994 0132 0842 0059 0852 D 807 0895 0059

P2RY12 rs6787801 A G 0499 994 0 120 0087 0448 0254 0067 0262 0067

P2RY12 rs6770918 G A 0063 964 0070 0831 0804 0622 0851 0476 0070

P2RY12 rs1388628 C G 0.226 994 0088 0.273 0089 0 191 0292 0225 0088

P2RY12 rs1491978 C T 0347 994 0159 0.230 0092 0831 0383 0.483 0092

P2RY12 re13090236 A T 0032 934 O 402 0018 0637 0041 0096 0 181 0096

P2RY12 re1466684 C T 0165 934 0.582 0318 0 120 0534 0.880 0902 0 120

P2RY12 re107551 OS A G 0396 994 0159 0381 0239 0609 0376 0452 0159

P2RY12 rs6440739 A G 0133 S94 0861 0794 0161 0877 0874 0616 0161

P2RY12 rs10935842 T A 0370 994 0863 0122 0569 0.236 0174 0327 0174

P2RY12 rs10513394 T C 0054 994 0709 0524 0175 0539 0749 0737 0175

P2RY12 rs9859538 G A 0441 994 0496 0232 0913 0115 0475 0 193 0193

P2RY12 rs6772253 T G 0045 994 0592 0613 0641 0543 0.534 0474 0474

PECAM1 NT_O1078314.21051616 C T 0461 994 0879 0542 0070 0813 0529 0478 0070

PECAM1 ra12953 A G 0487 992 0421 0266 0725 0684 0087 0492 0087

PECAM1 rs2070783 T C 0475 994 0945 0489 0125 0625 0517 0456 0 125

PECAM1 NT_010783 14_21052934 C T 0015 994 0482 0025 0535 0030 0149 0 133 0133

PECAM1 NT_010783 14_21092494 T C 0028 994 0145 0094 0848 0103 0225 0255 0145

PECAM1 re6808 G C 0483 994 0978 0538 0 180 0683 0488 0603 0180

PECAM1 rs4968725 A G 0.482 994 0777 0628 0652 0879 0.211 0753 0211

PECAM1 NT_01078314.21115565 G A 0.004 994 0422 0858 0768 0481 0568 0271 0.271

PECAM1 r$11652497 T C 0039 992 0909 0614 0608 0411 0503 0301 0301

PFKL rs2838551 C A 0376 994 0381 0999 0001 0301 0866 0281 0001

PFKL rs11701842 G A 0381 994 0596 0938 0004 0317 0650 0367 0004

PFKL rs4818908 G A 0144 994 0193 0 183 0018 0575 0866 0517 0018

PFKL rs3761392 T G 0145 994 0028 0748 0175 0605 0623 0933 0028

PFKL rs933150 A G 0286 994 O 030 0499 0831 0976 0065 0418 0030

PFKL r52256817 A G 0382 994 0358 0021 0847 0132 0052 0310 0052

PFKL rs2096860 T G 0 160 994 0674 0351 0054 0987 0961 0381 0054

PFKL rs941405 G C 0345 994 0066 0725 0522 0840 0 180 0642 0066

PFKL πs878081 A G 0243 992 0075 0388 0989 0869 0310 0863 0075

PFKL rs2070572 A G 0368 994 0576 0188 0097 0 196 0128 0 167 0097

PFKL rs2105662 C T 0206 994 0 102 0962 0953 0711 0743 0644 0102

PFKL rs8130070 C T 0091 994 0112 0577 0437 0542 0936 0841 0112

PFKL rs734336 G A 0181 994 0986 0446 0116 0751 0952 0271 0116

PFKL rs1057034 C T 0393 994 0195 0080 0394 0319 0117 0494 0117

PFKL rs1003854 G A 0249 988 0147 0334 0 666 0670 0280 0647 0147

PFKL rs11909068 A G 0 157 994 0147 0612 0 164 0954 0 896 0663 0 147

PFKL rs8129937 A G 0296 994 0 161 0195 0909 0883 0 160 0986 0 160

PFKL rs8134520 A G 0 159 994 0 175 0 916 0896 0619 0239 0788 0175

PFKL rs760426 G A 0138 994 0531 0092 0946 0282 0 189 0544 0169

PFKL re2838S49 T C 0090 994 0862 0400 0204 0 159 0994 0405 0204

PFKL rs2838S50 T A 0332 994 0206 0499 0874 0634 0247 0754 0206

PFKL rs2075876 T C 0107 994 0625 0739 0240 0799 0567 0666 0240

PFKL rs928303 G C 0 186 994 0559 0215 0734 0974 0244 0709 0244

PFKL rs2838544 T C 0248 994 0295 0532 0389 0685 0325 0506 0295

PFKL rs2070573 A C 0 191 994 0717 0266 0604 0961 0321 0696 0321

PFKL rs2276249 A G 0 139 988 0568 0096 0833 0432 0515 0823 0515

PFKL rs4350841 C T 0226 994 0828 0067 0533 0122 0579 0682 0533

PFKL rs2850161 T G 0 381 994 0812 0920 0600 0826 0624 0566 0566

PFKL rs2850163 A C 0450 994 0594 0917 0 757 0951 0869 0976 0594 PFKL 152850166 A G 0357 990 0808 0836 0831 0737 0735 0632 0632

PFKL re8127824 O T 0000 994

PIK3CB NT_00Sβ12 14_44973018 C T 0020 994 0399 0264 0075 0051 0232 0038 0038

PIK3CB rs17548850 T G 0191 994 0070 0677 0470 0963 0273 0710 0O7D

PIK3CB rs3729781 T C 0001 990 0888 0923 0369 0-249 0.490 0078 0078

PIK3CB NT_005612.14_44878167 T G 0029 994 0144 0458 0193 0525 0332 0452 0 144

PIK3CB rs497900 C T 0460 992 0534 0521 0416 0912 0835 0345 0345

PIK3CB rs3610β8 C A 0461 994 0554 0492 0554 0948 0919 0483

P1K3CG NT_00793313_31695874 A G 0321 994 0848 0085 0576 0166 0033 0123 0033

PIK3CG NTJW793313_31709561 C A 0016 994 0043 0503 0363 0486 0070 0145 0043

PIK3CG NT_00793313_3170S371 G A 0037 994 0105 0541 0.234 0623 0 159 0282 0 105

PIK3CG rs3173908 T C 0257 994 0621 0080 0437 0088 0124 0159 0124

PIK3CG rs3729673 A G 0040 994 0145 0559 0218 0669 0947 0944 0145

PIK3CG re849389 T C 0060 990 0262 0154 0S82 0137 0525 0395 0262

PIK3CG NTJ30793313_31702896 T C 0062 994 0288 0136 0649 0125 0446 0350 0288

PIK3CG NT.007933 14.31692907 T G 0096 994 0342 0431 0511 0418 0521 05S1 0342

P1K3CG ra12667819 A G 0459 994 0466 0732 0654 0707 0920 0858 0466

PIK3CG NT.007933 13.31702638 G C 0034 994 0802 0971 0560 0778 0983 0774 0560

PIK3CG NT_O07933 13_31709265 o c 0000 994

PIP5K3 NT.00S40315_59430944 G T 0006 994 0453 0244 0053 0093 0016 0010 0010

PIP5K3 NT_00S40315_59429291 G A 0004 982 0044 0207 0107 0431 0251 0547 0044

PIP5K3 rs1866047 C G 0009 994 0076 0860 0837 0843 0413 0317 0076

PIP5K3 rs2304545 C T 0 155 994 0539 0650 0095 0541 0621 0516 0095

PIP5K3 rs11538998 A G 0 108 994 0201 0687 0099 0466 0598 0386 0099

PIP5K3 NT_00540315_59421947 G T 0009 994 0928 0224 0832 0326 0324 0475 0324

PIP5K3 [32289171 T C 0340 992 0360 0952 0338 0548 0900 0474 0338

P1P5K3 NT_005403 15_59394564 G T 0001 994 0956 0315 0414 0306 0371 0382 0371

PIP5K3 re16840913 C T 0033 994 0487 0522 0712 0365 0606 0417 0417

PIP5K3 NT_00540315_59422185 A G 0035 994 0632 0456 0818 0612 0966 0945 0632

P1P5K3 NT_005403 15_59409421 C T 0017 994 0633 0759 0899 0636 0703 0986 0633

PIP5K3 NT_00540315_59419164 O A 0000 994

PIP5K3 NT_00540315_S942S387 O T 0000 S94

PIP5K3 NT_00540315_59429S42 O G 0000 994

PIP5K3 NT_0054031S_59431038 O C 0000 994

PIPSK3 NT_00540315_59431892 O T 0000 994

PLA2G2A re2307246 T C 0220 992 0096 0080 0009 0027 0 164 0056 0009

PLA2G2A ra11677 A G 0116 992 0155 0954 0629 0820 0661 0962 0155

PLA2G2A rs2236772 A G 0031 994 0813 0874 0270 0740 0753 0970 0270

PLA2G2A rs11573162 0 C 0000 994

PLA2G4A rs12720549 G A 0006 970 0740 0585 0290 0040 0456 0016 0016

PLA2G4A rs2307198 C T 0025 994 0358 0480 0130 0926 0741 0589 0 130

PLA2G4A rs6690185 A G 0168 994 0 187 0 195 0342 0217 0305 0339 0 187

PLA2G4A rs969357 C T 0070 S94 0347 0356 060O 0455 0218 0375 0218

PLA2G4A «12720625 C T 0027 972 0447 0378 0261 0508 0380 0573 0261

PLA2G4A rs2307195 G A 0023 994 0339 0535 0268 0736 0836 0950 0268

PLA2G4A [S6661772 A G 0061 994 0912 0559 0618 0495 0514 0453 0453

PLA2G4A rs7S19192 G A 0287 994 0627 0436 0538 0984 0648 0715 0538

PLA2G4A TS12129917 T C 0285 994 0627 0464 0550 0970 0636 0706 0550

PLA2G4A rs12720691 0 A 0000 994

PLCB1 rs 16994453 T C 0 149 986 0300 0 185 0091 0032 0068 0010 0010

PLCB1 rs2295179 C T 0302 994 0078 0436 0027 0368 0979 0744 0027

PLCB1 rs5516421 A G 0164 994 0055 0202 0080 0295 0 404 0555 0055 PLCB1 rs1047383 C T 0410 994 0.282 0157 0541 0237 0064 0165 0064

PLCBI rs6133609 C T 0014 994 0070 0600 0.210 0882 0112 0377 0070

PLCB1 rs1047381 A G 0360 S92 009S 0127 0211 0322 0072 0315 0072

PLCB1 [S2O766S0 T C 0183 994 0357 0504 0.077 0176 0695 0243 0077

PLCB1 rs3761170 A G 0078 994 0803 0 S54 0685 0533 0226 0.084 0084

PLCB1 NTJM 13878_8802593 G A 0018 994 0982 0744 0584 0443 0547 0.091 0091

PLCB1 rs605612β G C 0027 994 0405 0369 0491 0172 0.328 0131 0131

PLCB1 rs207S689 C A 0 129 994 0133 0422 0170 0464 0654 0705 0133

PLCB1 NT.0113878_8566859 A C 0170 962 0147 0827 0135 0728 0465 0504 0.135

PLCB1 rs8039269 T C 0290 994 0665 0602 0.383 0319 0289 0138 0138

PLCB1 rs5056043 A C 0091 994 0833 0969 0907 0452 0512 0190 0190

PLCB1 rsβ133622 A C 0371 994 0799 0S93 0584 0667 0282 0197 0197

PLCB1 re6088714 C T 0499 994 0747 0218 0201 0.289 0400 0505 0201

PLCB1 NT.0113878_8885826 G A 0022 994 0221 0943 0273 0949 0658 0765 0.221

PLCB1 RS608B550 G A 0342 994 0275 0547 0224 0645 0407 0579 0224

PLCB1 rs6086551 G A 0237 994 0231 0810 0845 0471 0793 0701 0.231

PLCB1 rs3761168 G T 0497 972 0364 0-985 0234 0468 0569 0647 0.234

PLCB1 ra2206266 T C 0499 994 0877 0228 0252 0297 0415 0515 0.252

PLCB1 rs2076639 T G 0477 994 0573 0104 0725 0128 0269 0299 0269

PLC B1 NT_O11387 β_8723171 G A 0012 994 0483 0767 0775 0388 0632 0277 0277

PLCB1 rs2235613 A G 0395 994 0516 0996 0.724 0818 0318 0321 0318

PLCB1 rs2076409 A G 0242 Θ94 0328 0870 0685 0779 0390 0412 0328

PLCB1 rs993670 G A 0020 992 0568 0914 0375 0631 0685 0415 0375

PLCB1 rs6086663 C G 0211 988 0512 0754 0384 0867 0716 0478 0384

PLCB1 !>Tr_0113878_8β02654 T A 0002 994 0996 0925 0662 0.626 0831 0416 0416

PLCB1 rs2327089 G A 0039 994 0498 0960 0695 0823 0837 0655 0498

PLCB1 rs2235612 A T 0317 994 0860 0506 0552 0381 0679 0583 0552

PLCB1 rs6O39315 T G 0282 994 0633 0736 0999 0839 0864 0850 0633

PLCB1 rs1015171 C T 0418 994 0941 0 784 0968 0985 0760 0645 0645

PLCB1 rs17446441 G A 0326 994 0782 0476 0831 0409 0724 0956 0724

PLCB 1 rs2294597 A G 0300 994 0903 0582 0889 0509 0979 0737 0737

PLCB1 rs6056118 G A 0339 992 0868 0595 0775 0583 0984 0877 0775

PLCB 1 rs2235947 T C 0313 994 0809 0730 0794 0788 0922 0923 0794

PLCB1 NT_0113878_8709293 O T 0000 994

PLCB1 NT_0113878_880S081 O G 0000 994

PLCG2 rs4354929 G C 0395 994 0919 0114 0339 0110 0025 0047 0025

PLCG2 rs7187863 G A 0227 994 0316 0067 0614 0437 0033 0483 0033

PLCG2 NT_O10498 15_35555692 C T 0019 992 0745 0998 0036 0 187 0918 0 111 0036

PLCG2 rs12596639 T C 0179 994 0528 0 151 0680 0 111 0052 0050 0050

PLCG2 rs6S64928 A C 0241 994 0390 0210 0634 0383 0133 0368 0133

PLCG2 rs7188701 G C 0177 994 0853 0932 0904 0277 0762 0158 0158

PLCG2 rs13333348 T C 0072 994 0419 0382 0680 0166 0491 0184 0184

PLCG2 rs4586426 T C 0344 994 0987 0928 0185 0836 0351 0405 0185

PLCG2 rs4405546 C A 0080 994 0966 0 112 0376 0488 0 191 0789 0 191

PLCG2 rs17626801 A G 0363 992 0931 0061 0821 0128 0244 0357 0244

PLCG2 rs4243221 C T 0235 994 0258 0350 0824 0301 0610 0472 0258

PLCG2 rs4072831 G A 0336 994 0733 0034 0471 0 144 0259 0597 0259

PLCG2 NT_01049815_35518467 G C 0071 994 0875 0822 0265 0468 0910 0592 0265

PLCG2 rs 16955980 A C 0377 994 0848 0067 0371 0177 0278 0529 0278

PLCG2 re4889419 A G 0210 994 0620 0175 0342 0372 0281 0562 0281

PLCG2 rs4258608 G A 0261 994 0923 0299 0812 0222 0393 0300 0300

PLCG2 NT 010498 15_35560567 C A 0 111 994 0635 0565 0617 0232 0929 0365 0365 PLCG2 rs3813009 G C O.21S Θ92 0959 0475 0692 0673 0377 0637 0377

PLCG2 NT_01O49B 15_35576730 G A 0 129 994 0377 0392 0524 0839 0418 0.972 0377

PLCG2 NT_01O49815_355O217β C G 0110 994 0816 0723 0813 0430 0875 0467 0.467

PLCG2 NT_01049815.35502473 T G 0079 994 0672 0594 0837 0491 0617 0490 0490

PICG2 rs17537869 T C 0058 994 0968 0994 0.549 0837 0791 0982 0549

PLCG2 NT_01(M9ai5_35571152 A C 0010 992 0652 0714 0944 0508 0857 0801 0652

PLCG2 NT_01049815_3SS55359 G A 0155 994 0728 0670 0835 0365 0701 0713 0701

PLCG2 rs12445580 T C 0381 Θ94 0931 0703 0.879 0490 0725 0859 0725

PLSCR1 rs.343320 T C 0088 994 0439 0623 0602 0282 0859 0OE6 0066

PLSCR1 Nr_005612 14_52746420 0 G 0000 Θ94

PPIA rs950355 A G 0.403 994 0003 0015 0334 0163 0021 0321 0003

PPIA 152825207 A T 0403 994 0003 0014 0300 0 118 0.017 0221 0003

PPIA re7276O4O C T 0.411 994 0014 0308 0056 0542 0328 0669 0014

PPIA rs997936 G C 0 175 994 0.617 0421 0032 0647 0.228 0472 0.032

PPIA rs2096970 A T 0.223 S94 0 119 0039 0331 0364 0043 0521 0043

PPIA C G 0 178 994 0052 0085 0583 0691 0066 0825 0052

PPIA «962363 T A 0389 994 0067 0521 0083 0563 0.565 0664 0.067

PPIA rs2825200 G A 0044 994 0072 0451 0629 0959 0364 0949 0072

PPIA rs1343760 C G 0179 994 0464 0062 0181 0303 0083 0458 0083

PPIA rs12482602 T C 0178 994 0474 0060 0157 0.282 0088 0448 0088

PPIA rs7282574 T C 0157 994 0944 0669 0108 0808 0225 0405 0108

PPIA rs1112111 A G 0134 994 0259 0 128 0353 0625 0120 0770 0120

PPIA rs2825203 G T 0134 994 0259 0 128 0.353 0625 0120 0770 0120

PPIA rs2243978 A G 0134 9S4 0J2S9 0128 0353 0625 0120 0770 0120

PPIA rs2406611 A G 0470 990 0128 0735 0708 0854 0347 0549 0 128

PPIA rs13051777 A G 0060 994 0304 0679 0634 0.612 0215 0259 0215

PPIA rs8132370 C T 0473 994 0279 0925 0315 0779 0548 0389 0279

PPIA rs13048541 T G 0013 994 0524 0364 0931 0799 0994 0572 0524

PPP2CA rs2300065 T A 0 147 994 0010 0202 0.476 0245 0681 0683 0010

PPP2CA NT_0347725_36951386 T A 0009 994 0180 0 133 0341 0165 0010 0036 0010

PPP2CA rs3776841 C A 0078 992 0090 0454 0744 0772 0572 0952 0090

PPP2CA rs10463916 G A 0059 992 0203 0134 0909 0260 0978 0856 0203

PPP2CA NT_0347725_35952532 G A 0022 994 0828 0162 0324 0262 0.241 0392 0241

PPP2CA rsi 1750335 A G 0028 994 0676 0908 0 Θ91 0914 0844 0877 0676

PRKACB rs787858 C A 0249 994 0051 0496 0026 0968 0978 0536 0026

PRKACB rs6703653 T C 0268 994 0814 0092 0410 0 129 0027 0071 0027

PRKACB rs12129768 G A 0112 994 0612 0033 0949 0119 0030 0173 0030

PRKACB rs6OO574 T C 0201 994 0032 0739 0073 0944 0 S95 0816 0032

PRKACB rs663521 A C 0228 994 0878 0248 0033 0599 0236 0683 0033

PRKACB rs970318 T C 0440 994 0204 0048 0612 0079 0036 0089 0036

PRKACB rs124θ4263 T C 0493 994 0182 0035 0430 0067 0037 0098 0037

PRKACB TS3861699 T C 0251 S94 0058 0501 0046 0729 0981 o eoo 0046

PRKACB rs2812447 G A 0235 994 0071 0436 0054 0586 0924 0967 0054

PRKACB rs11163932 A C 0299 994 0054 0524 0169 0699 0160 0396 0054

PRKACB rs1O874427 G C 0216 994 0545 0 175 0317 0141 00S5 0064 0055

PRKACB rs2892811 T C 0262 994 0932 0631 0056 0894 0 126 0572 0056

PRKACB rs12039822 A G 0246 S94 0091 0381 0058 0566 0616 0848 0058

PRKACB rs1016379 G A 0237 994 0063 0484 0073 0587 0990 0968 0063

PRKACB TS39O3924 G T 0486 994 0532 0097 0237 0317 0080 0391 0080

PRKACB rs12036564 G C 0246 992 0112 0509 0081 0681 0891 0951 0081

PRKACB C T 0 152 994 0838 0052 0448 0143 0083 0272 0083

PRKACB rs12122765 A G 0046 994 0235 0038 0919 0068 0083 0 155 0083 PRKACB rs12031680 A C 0322 994 0246 0172 0401 0 105 0124 0088 0088

PRKACB rs7S47B92 G A 0476 994 0089 0062 0.735 0098 0096 0 169 0089

PRKACB rs1057738 T G 0370 994 0331 OO7S 0.728 0 129 0097 0202 0097

PRKACB rs12O478S0 C A 0221 994 0125 0818 0.269 0.910 0.450 0856 0125

PRKACB rs171313O3 A G 0074 994 0278 0402 0603 0637 0 129 0381 0129

PRKACB rs957823 G T 0331 992 0264 0.229 0216 0127 0222 0131 0131

PRKACB CS752489B A G 0.043 990 0760 0416 0602 0645 0142 0401 0 142

PRKACB re12129674 A G 0 122 994 0940 0706 0318 0406 0303 0164 0164

PRKACB rs60681β A C 0074 994 0447 0611 0782 0824 0210 0480 0.210

PRKACB rs589373 T A 0082 994 0566 0817 0278 0666 0587 0244 0244

PRKACB rs11163895 T C 0045 994 0531 0897 0752 0895 0.299 0423 0299

PRKACB rs7S4682S A G 0179 994 0518 0334 0675 0393 0315 0429 0.315

PRKACB rs12728295 A G 0019 990 0555 0983 0320 0.896 0353 0575 0320

PRKACB re3729864 O A 0000 994

PRKCA NT.O1O783 14_23466487 T A 0497 994 0480 069O 0492 0668 0473 0688 0473

PRKCB1 NT_010393 14_15514782 A C 0001 994 096S 0017 0454 0075 0013 0098 0013

PRKCB1 NT_010393.15_15539394 T C 0007 994 0035 0348 0277 0270 0921 0765 0035

PRKCB1 NT_O1O39315_15541749 A C 0026 994 0798 0720 0431 0604 0089 0760 0089

PRKCB1 rs429813 A G 0280 994 0288 0873 0281 0957 0179 0432 0179

PRKCB1 rs7159349 G C 0072 994 0361 0537 0593 0783 0634 0186 0186

PRKCB1 rs223333β A G 0466 994 0687 0671 0189 0576 0521 0470 0189

PRKCB1 re3729898 C A 0004 992 0.214 0472 0.276 0610 0565 0742 0214

PRKCB1 NT_0103931S_15541472 G A 0067 994 0568 0378 0328 0217 0428 0230 0230

PRKCB1 rs198145 C T 0396 994 0559 0086 0332 0147 0.258 0372 0258

PRKCB1 rs3729BS6 A G 0037 994 0281 0836 0308 0825 0380 0541 0.281

PRKCB1 rs7196765 G A 0451 994 0648 0988 0356 0673 0749 0450 0356

PRKCB1 rs2239339 C G 0.183 994 0556 0778 0750 0601 0477 0374 0374

PRKCB1 rs4111O3 A T 0.388 994 0959 0495 0502 0232 0935 0412 0412

PRKCB1 NT.010393 14_15543583 T C 0017 994 0481 0476 0979 0984 0418 0958 0418

PRKCB1 NT_01039314J5312286 C T 0004 994 0423 0597 0648 0487 0762 0634 0423

PRKCB1 NT_01039315_15542778 T C O 074 994 0654 0141 0839 0149 0536 0445 0445

PRKCB1 NT.010393 15_15540807 G A 0033 994 0876 0564 0467 0858 0671 0972 0467

PRKCB1 NT.01O39315_15542272 T G 0011 988 0540 0292 0513 0477 0972 0876 0513

PRKCB1 rs3729885 C A 0049 994 0879 0181 0973 0340 0599 0844 0599

PRKCB1 rs3729883 G A 0462 994 0631 0401 0920 0455 0782 0812 0631

PRKCB1 NT_O1O39314_15S09347 O A 0000 994

PRKCD NT_022517 17_53161550 T C 0057 994 0013 0279 0 138 0171 0543 0317 0013

PRKCD re6764111 T C 0214 994 0023 0752 0379 0718 0696 0671 0023

PRKCD rs11130350 T G 0341 994 0 105 0628 0487 0525 0978 0772 0 105

PRKCD NT_O22517 17_53156064 A G 0021 992 0 129 0312 0251 0274 0217 0224 0 129

PRKCD rs2306574 G A 0210 994 0138 0523 0437 0441 0867 0690 0 138

PRKCD fs7630325 T C 0136 994 0824 0271 0962 0205 0526 0370 0370

PRKCD NT_O22517 16_53143018 A G 0268 S94 0925 0973 0966 0994 0876 0.886 0876

PRKCD NT_02251716_53139584 O A 0000 994

PRKCD NT_022517 17_53161405 O C 0000 976

PRKCD NT_022517 16_53145086 0 C 0000 992

PRKCE TS14138 A G 0 174 994 0339 0025 0573 0015 0045 0029 0029

PRKCE NT_0221B4 14_25053463 T C 0006 994 0051 0537 0991 0377 0721 0884 0051

PRKCE rs1987070 T G 0263 994 0 103 0407 0077 0788 0939 0304 0077

PRKCE rs935655 A C 0252 994 0156 0671 0116 0371 0449 0232 0116

PRKCE rs11680901 T C 0 128 986 0124 0235 0239 0974 0631 0420 0 124

PRKCE rs2595213 T C 0241 994 0469 0861 0271 0434 0552 0125 0125 PRKCE NT_O2218414_25021283 G A 0001 994 0 SO6 0519 0133 1766 0601 0533 0133

PRKCE NT.0221B414_25228885 G A 001S 994 0 133 0.604 0164 0358 0716 0417 0 133

PRKCE NT_02218414_25021128 A T 0013 994 0140 0160 0.944 0577 0315 0995 0140

PRKCE rs17034455 T C 00S1 994 0686 0951 0808 0552 0359 0163 0163

PRKCE 152278773 C G 0020 994 0279 0383 0753 0371 0 194 0231 0194

PRKCE rs281506 G A 0 138 994 0257 0726 0223 0886 0484 0754 0223

PRKCE rs10495929 A G 0136 994 0592 0420 0227 0273 0998 0604 0227

PRKCE FS4953294 A G 0291 994 0261 0541 0751 0870 0899 0773 0261

PRKCE rs672738β A G 0253 994 0281 0565 0434 0447 0820 0831 0.281

PRKCE NT_02218413_,24744637 T C 0006 994 0327 0324 0546 0.353 0517 0542 0327

PRKCE rs10191926 C T 0441 994 0418 0946 0343 0892 0370 0458 0343

PRKCE re7S57421 A G 0053 994 0849 0404 0561 0563 0344 0588 0344

PRKCE NT_022184 14_24740945 C T 0023 994 0954 0787 0399 0517 07S5 0774 0399

PRKCE rs2249633 G A 0314 978 0505 0625 0430 0792 0977 0427 0427

PRKCE rs2278774 G A 0020 992 0950 0971 0438 0783 0951 0746 0438

PRKCE NT_02218414_25021499 G C 0007 994 0900 0803 0439 0945 0491 0860 0439

PRKCE NT_02218413_25050573 C T 0012 994 0618 0315 0886 0688 0847 0469 0469

PRKCE rs10188306 C T 0207 990 0897 0439 0937 0460 0640 0605. 0605

PRKCE G A 0262 994 0805 0725 0819 0936 0916 0632 0632

PRKCE NT_02218413_251882S9 A G 0001 994 0817 0688 0989 0787 0974 0958 0817

PRKCE NT.02218414_2469S299 0 C 0000 994

PRKCE NT_02218414_24883670 O G 0000 994

PRKCE NT_0221β4 14_25021630 O T 0000 994

PRKCE NT_022184 14_2504463β o c 0000 994

PRKCG rs104203S8 G C 0418 994 0059 0545 0331 0610 0921 0923 0059

PRKCG rs307955 A G 0023 994 0 160 0547 0 163 0123 0461 0075 0075

PRKCG rs3745406 C T 0400 992 0085 0662 0516 0667 0895 0836 0085

PRKCG rs2242245 C T 0004 992 0995 097S 0 188 0891 0816 0741 0 188

PRKCG NT.O11109 15_26655403 A C 0013 994 0592 0269 0260 0162 0383 0917 0260

PRKCG NT.011109 15_26669792 G C 0043 994 0697 0264 0917 0377 0377 0497 0377

PRKCG rs2547362 O T 0000 976

PRKCG NT_011109 15_26676161 0 C 0000 992

PRKCH rs1088667 G C 0064 994 0908 0690 0706 0363 0146 0075 0075

PRKCH TS1092184 T A 0 186 994 0 110 0540 0204 0400 0555 0383 0110

PRKCH rs1088679 A G 0 136 994 0247 0528 0156 0614 0899 0927 0 156

PRKCH NT_026437 11,42923553 T G 0001 994 0 157 0725 0986 0621 0451 0758 0 157

PRKCH rs1088680 C T 0 149 994 0495 0420 0162 0571 0931 0962 0 162

PRKCH ra1092183 A G 0287 994 0 196 0767 0368 0427 0982 0515 0196

PRKCH rs10150621 T C 0020 994 0204 0943 0394 0992 0261 0391 0204

PRKCH rs2296275 C A 0013 992 0241 0713 0726 0931 0792 0922 0241

PRKCH rs1536016 T C 0034 994 0645 0819 0790 0635 0823 0343 0343

PRKCH r$3742633 G A 0140 994 0344 0323 0985 0456 0803 0908 0344

PRKCH rs2251380 C G 0035 992 0651 0701 0891 0776 0939 0442 0442

PRKCH NT_026437 11_42788945 T C 0071 994 0737 0616 0733 0807 0819 0722 0722

PRKCH NT_0Z6437 11_43014233 0 C 0000 994

PRKCQ rsβO4663 C T 0461 994 0087 0178 0346 0 115 0329 0215 0087

PRKCQ TS11258747 A C 0228 994 0251 0135 0628 0075 0199 0 112 0112

PRKCQ rs2453 T C 0258 994 0 150 0992 0318 0975 0965 0992 0150

PRKCQ rs7082071 T C 0231 984 0 171 0194 0584 0 124 0241 0 158 0 158

PRKCQ rs2236380 T C 0297 994 0584 0544 0596 0346 0290 0197 0197

PRKCQ NT_0775692_894384 T C 0009 990 0390 0500 0626 0889 0243 0990 0243

PRKCQ rs5391O3 C A 0023 994 0486 0389 0712 0473 0247 0383 0247 PRKCQ rs2236379 A G 0-257 994 0601 0344 0575 0771 0326 0.864 0.326

PRKCQ re4750528 G A 0164 994 0492 0945 0500 0785 0705 0986 0492

PRKCQ rs643610 A G 0186 994 0833 0273 0904 0235 0714 0571 0571

PRKCQ reS63798 T C 0119 994 0.901 0994 0653 0665 0621 0896 0621

PTGS1 rsS78β T G 0102 994 0669 0.056 0145 0613 0088 0962 0088

PTGS1 rs12555242 C T 0043 994 0626 0270 0105 0.231 0846 0.643 0105

PTGS1 rs4836885 G A 0104 990 0888 0109 0.200 0737 0 109 0,955 0109

PTGS1 rs10306194 T G 0154 994 0328 0103 0644 0378 0287 0790 0287

PTGS1 rs5794 T C 0007 992 052S 0603 0309 0872 0881 0599 0309

PTGS1 rs2282169 G C 0161 994 0535 0071 0708 0546 0322 0774 0322

PTGSI rs3842798 G A 0164 994 0652 0054 0608 0454 0369 0764 0369

PTGS1 rs8046 G A 0065 994 0687 0554 0387 0552 0382 0583 0382

PTGS1 rs5789 A C 0021 994 0725 0656 0403 0737 0.537 0769 0403

PTGS1 re1236913 T C 0074 992 0986 0346 0866 0663 0684 0920 0684

PTGS1 NT_00847017_32477897 O T 0000 994

PTGS2 reS277 C G 0172 994 0006 0575 0608 0826 0430 0775 0006

PTGS2 1320424 C G 0022 994 0069 0477 0941 0 138 0659 0 144 0069

PTGS2 rs4648276 C T 0123 994 0656 0295 0605 0 114 0202 0074 0074

PTGS2 rs2206593 T C 0052 994 0905 0767 0253 0554 0522 0363 0253

PTGS2 rs5275 G A 0330 994 0750 0816 0701 0814 0917 0569 0569

PTGS2 rsS272 O A 0000 994

PTK2 NT_O0804615_54886899 T A 0016 994 0157 0486 0022 0239 0228 0116 0022

PTK2 NT_008046 15_54887S02 A G 0002 994 0099 0408 0024 0147 0600 0210 0024

PTK2 NTJ3O8O4615_55074706 A T 0.068 994 0878 0.205 0344 0018 0488 0035 0035

PTX2 NT_0080461S_54992567 T C 0037 994 0066 0157 0301 0299 0 184 0383 0066

PTK2 NTJM8046 15_5489698S T C 0001 994 0713 0002 0607 0008 0078 0197 0078

PTK2 NT_0O8O461S_54887142 G A 0006 994 0646 0837 0235 0900 0656 0440 0235

PTK2 NT_00β04615_55155798 T C 0 148 994 0962 0647 0822 0 134 0783 0255 0255

PTK2 NT_0C804615_55155649 A G 0497 994 0371 0896 0599 0582 0624 0823 0371

PTK2 NT.00804615_55149347 A G 0004 994 0855 0858 0608 0597 0679 0433 0433

PTK2 NT_028251 11_6399599 T C 0312 994 0852 0583 0675 0210 0791 0434 0434

PTK2 NT_00804615_54929130 A G 0301 994 0693 0953 0817 0452 0531 0607 O531

PTK2 rs10875458 A C 0461 994 0546 0852 0640 0555 09B6 0564 0546

PTK2 rs443466β C T 0461 994 0546 0852 0640 0555 0986 0564 0546

PTK2 rs746O A T 0499 994 0840 0934 0693 0539 0692 0580 0580

PTK2 NT_028251 11_6399462 T C 0 139 994 0630 O B52 0868 0614 0718 0924 0630

PTK2 NT_00804615_54963443 T C 0456 994 0665 0924 0808 0739 0753 0753 0665

PTK2 NT.028251 11_6335816 T C 0001 994 0827 0306 0851 0464 0688 0856 0668

PTK2 NT_008046 15_55032053 0 C 0000 994

PTK2B rs919492 G T 0446 994 0221 0239 0018 0056 0 152 0028 0018

PTK2B rs10086852 G C 0451 994 0363 0228 0059 0054 0177 0034 0034

PTK2B rs7S1019 G T 0463 994 0222 0841 0064 0638 0540 0397 0064

PTK2B rs1030526 A G 0404 994 0329 0934 0071 0501 0560 0790 0071

PTK2B rs2278319 T C 0266 994 0661 0935 0086 0609 0 507 0X8 0086

PTK2B NT_02366617_S663411 T C 0442 994 0268 0769 0 100 0501 0900 0547 0100

PTK2B rs2241661 T G 0442 994 0268 0769 0100 0501 0900 0547 0100

PTK2B A G 0228 994 0694 0412 0103 0300 0284 0210 0103

PTK2B rs2241652 C T 0160 994 0915 0399 0725 0409 0 129 0 188 0 129

PTK2B NT_02356617_5651927 T C 0016 994 0357 0986 0416 0745 0 143 0456 0143

PTK2B NT_023666 16_5662599 C T 0147 994 0157 0459 0309 0486 0876 0 B14 0 157

PTK2B NT_023β6β 16_5667593 T G 0014 994 0868 0938 0170 0549 0815 0455 0170

PTK2B rs2241655 A G 0392 994 0327 0950 0204 0860 0949 0739 0204 PTK2B re7005244 G A 0428 992 0223 0.217 0598 0092 0877 0385 0223

PTK2B rs6988218 T A 0430 994 0228 0215 0555 0078 0837 0320 0.228

PTK2B rs7005936 T C 0388 994 0403 0988 0.257 0873 0946 0831 0.257

FTK2B re2241653 T A 0.157 994 0908 0106 0274 0255 0610 0885 0.274

PTK2B rs7482B2 T G 0146 994 0601 0717 0276 0677 0476 0488 0276

PTK2B rs7(X)714S T C 0398 994 0367 0846 0280 0951 0879 0695 0280

PTK2B rs748281 T C 0134 994 0454 0979 0281 0962 0882 0844 0281

PTK2B NT_02386617_5664303 G T 0017 994 0373 06S3 0354 0641 0445 0650 0354

PTK2B NT_0236651β_5683311 A G 0005 994 0476 0618 0945 0733 0888 0971 0476

PTK2B NT_023666 17_5557344 O T 0000 994

PTK2B NT_Q23δ6β 17_5662880 O G 0000 994

PTK2B NT_023666 17_566S976 o c 0000 992

PTK2B NT_02366β 17_5671188 O C 0000 994

PTPN11 NT_009775 14_3434176 T C 0079 994 0 131 0144 0142 0331 0868 0.690 0131

PTPN11 NT_009775 15_3460712 G C 0011 994 0 181 0231 0703 0.217 0451 0399 0181

PTPN11 NT.0097751S_351β148 T C 0022 994 0.754 0054 0743 0156 0342 0606 0342

PTPN11 NT.00977514_3443448 T C 0048 994 0838 0883 0622 0762 0766 0854 0622

PTPN11 NT.00977S 15_3489418 O A 0000 994

PTPN6 NT.009759 1S_6919795 T C 0003 994 0053 0704 0234 0325 0800 0574 0053

PTPN6 re10744724 G A 0055 992 0475 0373 0970 0642 0203 0213 0.203

PTPN6 rs759053 C T 0119 994 0623 0691 0320 0792 0303 0406 0303

PTPN6 rs11608598 A G 0406 994 0525 0080 0915 0148 0982 0995 0525

PTPNβ NT.00975915.6919697 O G 0000 992

RAC1 NT_00781915_5711286 C A 0132 994 0709 0166 0540 0303 0072 0209 0072

RAC1 rs3729796 C T 0008 994 0702 0.296 0854 0198 0098 0077 0077

RAC1 NT.007B1914_5726929 T G 0090 994 0467 0593 0816 0372 0287 0 175 0175

RAC1 rs6954996 T C 0027 992 0640 0449 0667 0518 0824 0 183 0183

RAC1 rs7O2483 A G 0451 994 0982 0939 0328 0581 0637 0720 0328

RAC1 rs836479 T G 0071 994 0394 0606 0849 0495 0737 0957 0394

RAC1 rs836S51 C G 0461 994 0918 0854 0532 0705 0663 0777 0532

RAF1 TS3729931 A G 0.368 994 0629 0773 0000 0496 0989 0280 0000

RAF1 rs5746223 G A 0102 994 0.223 0 135 0000 0010 0089 0004 0000

RAFI C G 0.229 994 0402 0595 0001 0153 0079 0012 0001

RAF1 rs1051208 T C 0141 994 0869 0402 0 180 0433 0053 0 116 0053

RAF1 rs2596831 C G 0429 994 0681 0909 0 146 0626 0224 0158 0 146

RAF1 rs2648367 G A 0.218 994 0978 0793 0 193 0876 0895 0596 0193

RAF1 NT.022517 16_12566223 O G 0000 994

RHOA rs3448 T C 0278 994 0889 0389 0446 0174 0720 0321 0321

PEAR1 rs3737224 A G 0092 994 0911 0215 0034 0010 0018 0000 0000

PEAR1 NT_004487 17_7373112 G C 0017 994 0461 0049 0094 0010 0001 0000 0000

PEAR1 NT_004487 17_7372314 A G ooβo 994 0984 0406 0091 0043 0050 0002 0002

PEAR1 re822442 T G 0 104 994 0845 0843 0017 0114 0253 0003 0003

PEAR1 re11264579 G A O ISO 994 0087 0207 0004 0231 0257 0319 0004

PEARI NT_004487 17_7370545 T G 0029 994 0480 0 753 0 030 0805 0613 0342 0030

PEAR1 NT_00448717_7374939 T C 0 140 994 0492 0020 O 048 0267 0342 0789 0048

PEAR1 rs4661012 G T 0389 990 0923 0210 0057 0728 0874 0 136 0057

PEAR1 rs12401524 T G 0096 994 0707 0421 0459 0242 0 124 0083 0083

PEAR1 TSS22441 C G 0 141 994 0145 0418 0519 0882 0814 0228 0145

PEAR1 rs11264581 A G 0195 994 0369 0005 0838 0080 0 158 0705 0 158

PEAR1 NT_004487 17_7375610 T C 0036 994 0420 0443 0508 0874 0 167 0626 0167

PEAR1 rs7492S6 A G 0268 994 0800 0 104 0913 0 104 0219 0212 0212

PEAR1 NT 004487 17 7373468 A G 0001 994 0217 0585 0651 0625 0910 0 318 0217 SELP rs6131 A G 0177 994 0081 0259 0185 0115 0259 0112 0081

SELP rs391774O T C 0190 994 0790 0176 0994 0096 0 178 0090 0090

SELP rs613S T C 0001 974 0.143 0794 0117 0534 0742 0233 0117

SELP G T 0126 994 0856 0939 0125 0402 0593 0 198 0 125

SELP rs3917729 A G 0120 994 0308 0076 0857 0180 0152 0353 0152

SELP rs6125 T C 0055 994 0299 0.559 0.171 0637 0993 0276 0171

SELP rs3917696 T C 0055 934 0299 0559 0171 0637 0993 0276 0171 sap rs3917739 G A 0367 994 0312 0S21 0537 0656 0 199 0406 0199

SELP rs2076O74 T C 0227 994 0903 0213 0271 0864 0226 0920 0226

SELP 13732314 A G 0477 994 0642 0731 0618 0302 0902 0335 0335

SELP rs6133 A C 0123 994 0825 0806 0335 0792 0911 0835 0335

SELP IS3917875 C G 0.005 994 0.869 0226 0544 0.217 0474 0433 0433

SELP re3917731 C T 0297 994 0676 0574 0738 0.695 0675 0829 0675

SHC1 rs3766921 C G 0030 S94 0962 0512 0971 0250 0128 0061 0061

SHC1 NT_0O448717_5432386 T C 0005 994 0570 0674 0577 0850 0671 0340 0340

SHC1 rs8191981 O C 994

SHC1 MT.004487 17_5437434 0 C 0000 994

SYK rs14979 A G 0027 992 0326 0260 0650 0095 0107 0039 0039

SYK ra176O124 C T 0219 994 0488 0097 0104 0055 0126 0071 0071

SYK rs1049164 A G 0186 994 0881 0.201 0807 0070 0305 0 103 0103

SYK rs914928 T C 0240 992 0530 0 156 0126 0 131 0119 0111 0111

SYK NT_00847614_9S0272 G A 0055 994 0464 0754 0575 0196 0694 0130 0130

SYK NT_00847β 14_929335 T C 0061 988 0 164 0 104 0813 0658 0205 0999 0164

SYK rs1756870S G T 0017 994 0499 0068 0 167 0546 0.295 0795 0167

SYK rs290227 T C 0248 992 0198 0051 0226 0017 0525 0172 0172

SYK rs29O228 C T 0 117 988 0635 0020 0410 0006 0600 0 175 0 175

SYK fs2306042 C T 0015 992 0236 0904 0973 0927 0408 0408 0236

SYK rs158688 G A 0345 994 0933 0 133 07B5 0142 0292 0290 0290

SYK TS2290890 A G 0125 992 0339 0588 0308 0805 0810 0520 0308

SYK rs2278275 C T 0346 994 0505 0973 0638 0664 0571 0377 0377

SYK rs11787670 C T 0068 994 0746 0451 0719 0330 0715 0476 0476

SYK ra158687 C T 0318 994 0681 0250 0668 0349 0591 0695 0591

SYK rs158689 A T 0452 994 0815 0653 OS45 0861 0627 0879 0627

TACC3 ra744β58 C T 0203 994 0302 0820 0975 0936 0016 0102 0016

TACC3 rs4865468 A G 0063 982 032S 0896 0025 0737 0608 0367 0025

TACC3 3135667 C G 0054 994 0248 0551 0028 0727 0536 0531 0028

TACC3 rs1665366 G A 0194 994 0382 0811 0879 0926 0031 0213 0031

TACC3 rs3752749 A G 0190 990 0356 0951 0831 0725 0034 0227 0034

TACC3 rs4577642 G C 0213 994 0.220 0442 0493 0833 0060 0380 0060

TACC3 rs1374468 A G 0214 994 0206 0422 0562 0895 0061 0454 0061

TACC3 rs17802841 C T 0197 994 0325 0535 0550 0947 0096 0493 0096

TACC3 G C 0484 994 0580 0503 0962 0601 0098 0238 0098

TACC3 NT_0376234_242157 A G 0046 994 0189 0677 0438 0627 0608 0605 0189

TACC3 rs223699S A C 0496 994 0226 0860 0583 0438 0207 0865 0207

TACC3 rs1063743 A G 0271 994 0582 0969 0534 0677 0904 0587 0534

TACC3 rs7680647 G A 0342 994 0891 0593 0973 0520 0701 0954 0701

TACC3 rs1530688 A G 0320 994 0764 0372 0973 0324 0911 0705 0705

TACC3 NT_0376234_245715 O G 0000 994

TBPL1 rs229908 G A 0298 S94 0063 0317 0012 0207 0233 0 163 0012

TBPL1 rs9375998 C T 0018 994 0017 0 133 0062 0223 0049 0 140 0017

TBPL1 G A 0266 994 0546 0 157 0044 0260 0040 0 139 0040

TBPL1 NT 025741 13 38408214 A C 0005 994 0271 0001 0642 0002 0053 0043 0043 TBPL1 re228857 C G 0445 994 0315 0129 0288 0396 0.0SΘ 0404 0088

TBPL1 rs127171 C T 0^35 994 0928 0174 0312 0.291 0091 0J233 0091

TBPL1 rs2811675 A G 0.444 994 0781 0154 0.234 0089 0 189 0111 0 111

TBPL1 rs17482529 T C 0032 994 0799 0136 0930 0393 0119 0493 0119

TBPL1 rs47137 C A 0435 994 0738 0061 0175 0057 0155 0141 0141

TBPL1 rs2811673 A C 0214 994 0858 0277 0230 0390 0141 0289 0141

TBPL1 rs229903 A G 0373 994 0197 0827 0680 0899 0.307 0475 0197

TBPU rs1217β172 C T 017Θ 994 0713 0165 0263 0094 0481 0^57 0.257

TBPL1 13380825 C T 0.471 994 0655 0035 0753 0107 0.282 0492 0282

TBPL1 rs170645 T C 0030 994 0308 0956 0814 0598 0625 0751 0308

TBPL1 rs220O2BS A G 0041 994 0313 0748 0642 0592 0526 0409 0313

TBPL1 rs19S0503 C T 0345 994 0920 0 149 0338 0468 0329 0819 0329

TBPL1 re93760O2 C A 0171 994 0390 0871 0Θ72 0451 0519 0830 0390

TBPL1 rs6902440 C T 0080 994 0884 0624 0407 0502 0760 0955 0407

TBPL1 rs3777899 C T 0080 994 0884 0624 0407 0502 0760 0955 0407

TBPL-I rs2627239 C A 0233 994 0587 0537 0547 0601 0419 0537 0419

TBPL1 r 59389124 G A 0399 994 0433 0139 0616 0.274 0472 0654 0433

TBPL1 rs9375994 A T 0422 994 0988 0082 0.574 0.241 0474 0.797 0474

TBPL1 rs9385675 C A 0366 994 0682 0333 0475 0507 0870 0982 0475

TBPL1 rs9373073 T G 0426 994 0951 0092 0614 0248 0478 0775 0476

TBPL1 rs2076583 C T 0447 990 0737 0 100 0767 0202 0627 0766 0627

TBPL1 rs459625 A G 0439 994 0953 0 124 0750 0272 0631 0851 0631

TBPL1 rs9402557 T C 0196 994 0851 0304 0716 0210 0.976 0664 0664

TBPL1 re9493783 0 G 0000 994

TBXA2R reS7S1 0 C 0000 992

TBXAS1 rs2072179 G A 0044 S94 0489 0006 0915 0003 0015 0008 O 0OS

TBXAS1 WT_007914 14_308885 C G 0001 994 0079 0967 0 110 0650 0800 0798 0079

TBXAS1 NT_00791414_167123 T C 0004 994 0230 0023 0.971 0031 0092 0105 0092

TBXAS1 rs6484448 G A 0123 994 0372 0632 0 122 0582 0826 0941 0122

TBXAS1 rs17263191 C T 0050 994 0865 0741 0701 0133 0896 0184 0184

TBXAS1 NTJW7914 14_163319 C T 0 171 992 0327 0 139 0326 0237 0663 0657 0326

TBXAS1 rs5763 A C 0014 994 0931 0037 0835 0050 0344 0329 0329

TBXAS1 NT.00791413_244723 A G 0204 994 0360 0440 0936 0885 0895 0423 0360

TBXAS1 rs8192827 C T 0034 994 0640 0317 0429 0315 0628 0587 0429

TBXAS1 NT_00791414_72248 G T 0001 994 0471 0369 0501 0450 0521 0618 0471

TBXAS1 NT_0O7914 14_2O4716 C T 0023 992 0485 0831 0548 0801 0638 0822 0485

TBXAS1 rs10242928 A T 0 101 994 0742 0819 0771 0538 0806 0515 0515

TBXAS1 NT_∞7914 14_204366 A T 0011 994 0977 0.721 0802 0870 0572 0810 0572

TBXAS1 rs10255449 0 T 0000 994

TBXAS1 rs6138 0 C 0000 994

TBXAS1 NT_007914 14_246714 O A 0000 994

TBXAS1 NT_007914 13_248864 0 G 0000 994

TBXAS1 rs5760 0 G 0000 994

TBXAS1 NT.007914 14_311202 0 G 0000 992

TEC NT_006238 10_78804Q6 C T 0428 994 0418 0454 0071 0407 0270 0285 0071

TEC NT_006238 10_7849694 C T 0370 994 0087 0968 0105 0858 0985 0886 0087

TEC rs2071027 G A 0335 994 0396 0389 0 150 0525 0566 0562 0150

TEC NT_OOS238 10_7840137 G A 0323 994 0358 0513 0195 0591 0403 0496 0195

TEC NT_006238 10_7874137 T C 0332 994 0477 0583 0234 0667 0324 0414 0234

TEC NT.006238 10_7875137 G A 0334 994 0493 0476 0253 0558 0398 0492 0253

TEC NT_006238 10_7973652 C G 0 143 994 0969 0 363 0260 0648 0350 0718 0260

TEC rs2271173 T C 0329 988 0406 0595 0313 0 584 0285 0469 0285 TEC NT_00623810_7871929 A G 0.238 994 0829 0089 0363 0.098 0688 0591 0363

TEC NT_00623810.7840437 T C 0.257 994 0664 0072 0392 0080 0713 0569 0392

TEC NTJM623810_7841249 C A 0257 994 0664 0072 0392 0080 0713 0569 0392

TEC NT_00623810_784O456 G C 0022 994 0670 0399 0.688 0.202 0905 0.457 0.457

THBS1 rs9920929 A G 0034 994 0150 0395 0252 0024 0385 0013 0013

THBS1 NT_010194 16.10669135 A G 0012 994 0202 0678 0050 0338 0466 0880 0050

THBS1 rs17632916 G A 0 164 994 0332 0714 0292 0484 0688 0137 0137

THBS1 rs1051442 A G 0 164 994 0332 0714 0292 0484 0688 0137 0 137

THBS1 rs22282S2 6 A 0 113 994 0846 0512 0927 0735 0647 0163 0 163

THBS1 rs2664141 A G 0289 994 0508 0809 0236 0721 0844 0414 0.236

THBS1 NT.0101941β_108β8025 T A 0007 992 0473 0016 0375 0039 0695 0715 0375

THBS1 rs753599 T C 0126 994 0631 0954 0731 0726 0917 0591 0591

THBS1 ra22923O5 C T 0128 994 0767 0912 0675 0813 0916 0759 0675

THBS1 NT_010194 16_10675626 O T 0000 994

TLN1 rs3829078 G A 0119 994 0086 0050 0162 0078 0024 0067 0024

TLN1 C T 0281 994 0024 0792 0484 0978 0702 0940 0024

TLN1 NT_008413 16_35689546 T C 0001 994 0670 0048 0658 0070 0028 0081 002S

TLN1 NT.00B413 16_3S700904 C G 0001 994 0031 0329 0079 0493 0066 0221 0.031

TLN1 rs10814270 T C 0064 994 0.514 0377 0.035 0678 0825 0826 0035

TLN1 rs1998308 A T 0344 994 00S8 0378 0039 0360 0706 0616 0039

TLN1 rs10972567 A C 0402 994 0.120 0286 0.044 0 180 0253 0168 0044

TLN1 rs741917 T C 0281 992 0045 0927 0520 0722 0884 0836 0045

TLN1 ra1O972558 G C 0230 994 0048 0989 0601 0643 0705 0775 0048

TLN1 NT_00841316.35722528 G A 0026 994 0063 0924 0709 0405 0823 0221 0063

TLN1 ra3793537 C G 0291 994 0798 0798 0065 0606 0621 0494 0065

TLN1 re2857802 C T 0375 994 0067 0870 0515 0871 0922 0789 0067

TLN1 π>2295795 A G 0289 994 0871 0600 0069 0422 0524 0384 0069

TLN1 rs2O7167β T C 0343 994 0081 0555 0354 0878 0262 0640 0081

TLN1 rs1534847 G A 0293 994 0684 0410 0086 0.269 0432 0298 0086

TLN1 rs2236288 G C 0217 994 0999 0746 0089 0424 0268 0156 0089

TLN1 G T 0.457 994 0 197 0330 0092 0349 0407 0453 0092

TLN1 A G 0282 994 0584 0328 0 105 0.235 0397 0297 0 105

TLM A G 0 186 994 0838 0696 0 107 0797 0540 0281 0 107

TLN1 rs11541908 T C 0279 994 0852 0601 0114 0420 0574 0406 0 114

TLN1 rs10814274 A G 0422 994 0126 0675 0476 0980 0775 0509 0 126

TLN1 ra1951432 A G 0341 992 0137 0484 0446 0451 0415 0447 0 137

TLN1 NT.008413 16_35709720 T C 0001 994 0142 0575 0931 0803 0884 0709 0 142

TLN1 NT.00B413 16,35688942 T C 0022 994 0165 0546 0202 0910 0942 0448 0165

TLN1 rs224925O G T 0317 994 0903 0214 0167 0125 0413 0237 0167

TLN1 NT_008413 16_35701405 T C 0005 994 0832 0377 0947 0416 0181 0241 0181

TLN1 rs1243874 A T 0016 994 0237 0517 0917 0211 0983 0402 0237

TLN1 rs4879924 G A 0144 994 0641 0752 0746 0831 0287 0856 0287

TLN1 NT_008413 16_35722357 G C 0009 994 0298 0136 0769 0403 0577 0942 0298

TLN1 rs7858447 C T 0 163 994 0304 0263 0329 0292 0497 0495 0304

TLN 1 rs4879923 C T 0366 994 0860 0130 0466 0084 0518 0313 0313

TLN 1 rs3763629 C T 0096 994 0337 0772 0819 0909 0320 0583 0320

TLN1 NT_008413 16_3S697677 A G 0056 994 0714 0790 0509 0694 0394 0672 0394

TLN1 rs7853785 C G 0048 994 0611 0896 0406 0617 0677 0667 0406

TLN1 NT_008413 16_35698425 G A 0019 906 0954 0787 0803 0893 0609 0951 0609

TLN1 rs2071675 A G 0066 994 0717 0965 0611 0882 0831 0706 0611

TLN 1 NT_008413 16_35697582 0 C 0000 994

TLN1 NT 008413 16 35709509 O G 0000 994 TUBB1 re10485828 C G 0204 994 0571 0.113 0965 0120 0.348 0304 0304

TUBB1 MT_011362.9_226475S0 T C 0041 994 0421 0588 0857 0979 0.693 0781 0421

TUBB1 rsβ070697 T C 0 192 994 0766 0472 0924 0700 0450 0692 0450

TUBB1 NT_011362.9_22651704 T C 0001 994 0.716 0694 0642 0692 0953 0959 0642

VAV1 ra186295 T C 0 124 992 0534 0046 0979 0015 0021 0007 0007

VAV1 rs7258040 A G 0 125 994 0703 0629 0049 0755 0355 0546 0049

VAV1 ra347O33 G A 0175 994 0396 0.276 0053 0439 0323 0545 0053

VAV1 MT_011255 14_6797430 T C 0006 994 0176 0601 0055 0637 0493 0587 0055

VAV1 rs331679 T C 0284 994 0297 0085 0456 0277 0 100 0425 0 100

VAV1 NT_011255 14_6790767 T C 0086 994 0756 0122 0577 0477 0137 0669 0 137

VAV1 rs625828 A T 0448 994 0863 0394 0721 0445 0895 0919 0721

VAV1 NT_01125514_6788058 O C 0000 994

VAV3 NT_01927317_422SO76 G A 0058 994 0001 0228 0097 0375 0136 0336 0001

VAV3 ra12410842 A G 0.059 994 0005 0144 0 126 0260 0083 0.237 0005

VAV3 rs276S66θ T C 0059 994 0005 0 144 0 128 0260 0083 0237 0005

VAV3 rs7416884 G C 0366 984 0023 0953 0600 0687 0772 0497 0023

VAV3 rs12403266 G C 0182 994 0087 0619 0308 0638 0382 0479 0087

VAV3 NT_01927317_4378128 C T 0030 948 0720 0299 0716 0615 0154 0531 0 154

VAV3 rs2494069 G A 0218 994 0242 0821 0179 0669 0966 0758 0179

VAV3 NT_O1927317_43β4116 C G 0009 994 0251 0972 0196 0708 0927 0596 0198

VAV3 «7516071 G A 0154 922 0366 0903 0211 0616 0610 0406 0211

VAV3 r5229β877 T G 0163 994 0.550 0077 0569 0266 0252 0616 0252

VAV3 rs6672483 T C 0381 994 0252 0874 0310 0861 0463 0586 0252

VAV3 rs17020006 C T 0010 994 0.311 0937 0.293 0800 0879 0629 0293

VAV3 «2494070 G A 0394 952 0613 0809 0900 0732 0305 0329 0305

VAV3 NT.019273 17_4397382 C A 0009 992 0366 0042 0898 0320 0316 0974 0316

VAV3 rs6583048 C T 0208 994 0412 0380 0672 0959 0340 0929 0340

VAV3 NT_01S273 17_4202166 A G 0038 994 0464 0398 0942 0307 0427 0344 0344

VAV3 fs7528153 T A 0288 994 0997 0931 0760 o τπ 0969 0669 066S

VIPR1 rs8913 G A 0465 9S4 0099 0618 0157 0816 0811 0967 0099

VIPR1 rs9677 A G 0477 994 0225 0203 0153 0 114 0585 0295 0 153

VIPR1 rs406360 C T 0370 994 0457 0966 0663 0243 0943 0156 0 156

VIPR1 rs342511 G A 0480 994 0186 0765 0663 0910 0908 0617 0186

VIPR1 NTJJ22517 17_42518415 G C 0001 994 0937 0669 0571 0610 0674 0 187 0187

V1PR1 rs2276829 C G 0141 994 0527 0124 0456 0285 0197 0460 0197

VIPR1 rsS96 A G 0440 994 0343 0400 0765 0277 0276 0202 0202

VIPR1 re168207 A G 0467 994 0255 0819 0794 0903 0887 0648 0255

VIPR1 NTJK2517 16_42499014 T C 0012 994 0296 0681 0632 0982 0833 0812 0296

VIPR1 rs413042 C G 0022 994 0977 0898 0342 0838 0392 0301 0301

VIPR1 NT_O22S17 16_42S02634 T G 0015 994 0581 0343 0996 0834 0733 0687 0581

VIPR1 NT 022517 16 42SO2534 0 G 0000 994 References

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2. Farndale RW, Siljander PR, Onley DJ, Sundaresan P, Knight CG, Barnes MJ. Collagen-platelet interactions: recognition and signalling. Biochem Soc Symp. 2003:81-94.

3. Farndale RW, Sixma JJ, Barnes MJ, de Groot PG. The role of collagen in thrombosis and hemostasis. J Thromb Haemost. 2004;2:561-573.

4. Moroi M, Jung SM, Okuma M, Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest. 1989;84:1440-1445.

5. Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001;409:202-207.

6. Jones C, Garner, SF, Angenent, W, Bernard, A, Berzuini, C, Burns, P, Farndale, RW, Hogwood, J, Rankin, A, Stephens, JC, Tom, BD, Walton, J, Dudbridge, F, Ouwehand, WH and Goodall, AH. Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus. Journal of Thrombosis and Haemostasis, 5: 1756-1765, 2007;Epub, ahead of publication.

7. O'Donnell CJ, Larson MG, Feng D, et al. Genetic and environmental contributions to platelet aggregation: the Framingham heart study. Circulation. 2001;103:3051-3056.

8. Gaxiola B, Friedl W, Propping P. Epinephrine-induced platelet aggregation. A twin study. Clin Genet. 1984;26:543-548.

9. Macaulay IC, Carr P, Gusnanto A, Ouwehand WH, Fitzgerald D, Watkins NA. Platelet genomics and proteomics in human health and disease. The Journal of Clinical Investigation. 2005 115:3370-3377.

10. Gnatenko DV, Dunn JJ, McCorkle SR, Weissmann D, Perrotta PL, Bahou WF. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood Cells, Molecules, and Disease. 2003;101:2285-2293.

11. Bugert P, Dugrillon A, Gϋnaydin A, Eichler H, Kliiter H. Messenger RNA profiling of human platelets by microarray hybridization. Thrombosis and Haemostasis. 2003;90 738-748.

12. Newland SA, Macaulay IC, Floto RA, et al. The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro. Blood. 2007;prepublished online February 20, 2007; DOI 10.1182/blood-2006-09- 047449.

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Claims

Claims

1. An in vitro method of diagnosing whether a subject has, or is at risk of, an abnormal blood condition, which comprises determining the genotype of the subject at a single nucleotide polymorphism (SNP) position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response.

2. A method according to claim 1, wherein the abnormal blood condition is associated with an increased risk of thrombosis.

3. A method according to claim 1, wherein the abnormal blood condition is associated with an increased risk of bleeding.

4. A method according to any preceding claim, wherein the gene associated with platelet response is specifically associated with adenosine-di-phosphate (ADP)- stimulated platelet activation, collagen-related peptide (CRP)-stimulated platelet activation, or ADP- and CRP-stimulated platelet activation.

5. A method according to claim 4, wherein the gene specifically associated with ADP-stimulated platelet activation is any of the following genes: RAFl, JAK2, P2RY12, GNAZ, VAV3, PFKL, ITGA2, ITPRl, MAP2K2, MAPK14, MADD, MAP2K1, PTGS2, or MAP2K5.

6. A method according to claim 4, wherein the gene specifically associated with CRP-stimulated platelet activation is any of the following genes: GP6, GNAl 2, FCERlG, CD36, AKT2, MAP2K4, VAVl, TBXASl, INSR, CDC42, or LAT.

7. A method according to claim 4, wherein the gene specifically associated with ADP- and CRP-stimulated platelet activation is any of the following genes: PEARl, C0MMD7, GAS6, PLA2G2A or PLCBl.

8. A method according to claim 5, wherein the SNP position is selected from any of the following: position rs3729931 of RAFl; position rslO429491 of JAK2; position rsl472122 of P2RY12; a position corresponding to position NT_011520.10_2802586 of GNAZ SEQ ID NO: 1; a position corresponding to position NT_019273.17_4225076 of VAV3 SEQ ID NO: 2; position rs2838551 of PFKL; position rs41305896 of ITGA2; position rs41304179 of ITPRl; position rs350916 of MAP2K2; position rs851007 of MAPKl 4; position rs41304345 of MADD; position rsl l637556 of MAP2K1; position rs5277 of PTGS2; or position rsll631474 of MAP2K5.

9. A method according to claim 6, wherein the SNP position is selected from any of the following: position rsl613662 of GP6; position 41304915 of GNA12; position rs3557 of FCERlG; position rslO49654 of CD36; position rs41275750 of AKT2; position rs41307923 of MAP2K4; position rsl86295 of VAVl; position rs2072179 of TBXASl; position rs6510959 of INSR; position rs7544500 of CDC42; or position rsl 802141 of LAT.

10. A method according to claim 7, wherein the SNP position is selected from any of the following: position rs3737224 of PEARl; position rs6141803 of C0MMD7; position rs41307142 of GAS6; position rs2307246 of PLA2G2A; or position rsl6994453 of PLCBl.

11. A method according to any preceding claim, wherein it is determined whether the subject is homozygous or heterozygous for an allele at the SNP position.

12. A method according to any preceding claim, wherein the subject is a Caucasian.

13. An oligonucleotide probe capable of specifically detecting an allele at a SNP position in a gene associated with platelet response, wherein the allele is associated with enhanced platelet response, or wherein the allele is anti-thetical to an allele that is associated with enhanced platelet response.

14. A probe according to claim 13, wherein the gene associated with platelet response is specifically associated with adenosine-di-phosphate (ADP)-stimulated platelet activation, collagen-related peptide (CRP)-stimulated platelet activation, or with ADP- and CRP-stimulated platelet activation.

15. A probe according to claim 13, wherein the gene specifically associated with ADP-stimulated platelet activation is any of the following genes: RAFl, JAK2, P2RY12, GNAZ, VAV3, PFKL, ITGA2, ITPRl, MAP2K2, MAPK14, MADD, MAP2K1, PTGS2, or MAP2K5.

16. A probe according to claim 13, wherein the gene specifically associated with CRP-stimulated platelet activation is any of the following genes: GP6, GNA12, FCERlG, CD36, AKT2, MAP2K4, VAVl, TBXASl, INSR, CDC42, or LAT.

17. A probe according to claim 14, wherein the gene specifically associated with ADP- and CRP-stimulated platelet activation is any of the following genes: PEARl, C0MMD7, GAS6, PLA2G2A or PLCBl.

18. A probe according to claim 15, wherein the SNP position is selected from any of the following: position rs3729931 of RAFl; position rslO429491 of JAK2; position rsl472122 of P2RY12; a position corresponding to position NTJ)11520.10J2802586 of GNAZ SEQ ID NO: 1; a position corresponding to position NT_019273.17_4225076 of VAV3 SEQ ID NO: 2; position rs2838551 of PFKL; position rs41305896 of ITGA2; position rs41304179 of ITPRl; position rs350916 of MAP2K2; position rs851007 of MAPK14; position rs41304345 of MADD; position rsll637556 of MAP2K1; position rs5277 of PTGS2; or position rsl 1631474 of MAP2K5.

19. A probe according to claim 16, wherein the SNP position is selected from any of the following: position rsl613662 of GP6; position 41304915 of GNA12; position rs3557 of FCERlG; position rslO49654 of CD36; position rs41275750 of AKT2; position rs41307923 of MAP2K4; position rsl86295 of VAVl; position rs2072179 of TBXASl; position rs6510959 of INSR; position rs7544500 of CDC42; or position rsl 802141 of LAT.

20. A probe according to claim 17, wherein the SNP position is selected from any of the following: position rs3737224 of PEARl; position rs6141803 of C0MMD7; position rs41307142 of GAS6; position rs2307246 of PLA2G2A; or position rsl6994453 of PLCBl.

21. A kit for diagnosing whether a subject has, or is at risk of, an abnormal blood condition, which comprises means for determining the genotype of the subject at a SNP position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response, or is anti-thetical to an allele that is associated with enhanced platelet response.

22. A kit according to claim 21, wherein the determining means comprises a probe according to any of claims 13 to 20.

23. A kit according to claim 21 or 22, wherein the abnormal blood condition is associated with an increased risk of thrombosis.

24. A kit according to claim 21 or 22, wherein the abnormal blood condition is associated with an increased risk of bleeding.

25. Use of a probe according to any of claims 13 to 20, or a kit according to claim 21 or 22, for the diagnosis of an abnormal blood condition.

26. Use according to claim 25 for the diagnosis of an abnormal blood condition associated with an increased risk of thrombosis.

27. Use according to claim 25 for the diagnosis of an abnormal blood condition associated with an increased risk of bleeding.

28. Use of a method according to any of claims 1 to 12, a probe according to any of claims 13 to 20, or a kit according to claim 21 or 22, to identify subjects for participation in a clinical trial to assess a drug candidate for treatment of an abnormal blood condition.

29. A method of preventing, treating, or ameliorating an abnormal blood condition, which comprises determining the genotype of the subject at a single nucleotide polymorphism (SNP) position in a gene associated with platelet response, wherein an allele of the SNP is associated with enhanced platelet response, and administering an appropriate prophylactic or treatment, or adjusting an ongoing prophylactic or treatment course, based on the result of the determination.

30. A method according to claim 29, wherein the prophylactic or treatment is a platelet inhibitor.

31. A method according to claim 29 or 30, wherein the prophylactic or treatment is specific for adenosine-di-phosphate (ADP)-stimulated platelet activation, collagen- related peptide (CRP)-stimulated platelet activation, collagen-stimulated platelet activation, or ADP- and CRP-stimulated platelet activation.