Abstract 20907: A Genome-Wide Association Study Identifies an Association between a Genetic Variant in the MET Receptor Gene and Collagen-induced Platelet Aggregation
Variations in platelet function among individuals are partly due to genetic factors. While previous GWAS have examined platelet function in platelet-rich plasma, we report here results of the first GWAS of platelet function in whole blood. Study and replication samples consisted of 1245 Caucasians and 843 African Americans (AA) respectively. Whole blood impedance aggregometry after collagen-induced (1 ug/mL) platelet aggregation was used to measure lag-time, slope, and maximal aggregation. Genotyping was performed with the Illumina 1M BeadChip array. Linear mixed effects models were used to test for association between each SNP and platelet phenotypes. Analyses were adjusted for age, sex, cardiac risk factors and population stratification. Due to high correlation between maximal aggregation and slope(r=0.76), we combined these two phenotypes by performing meta-analysis with tetrachoric correlation. We identified an association between a SNP in the 2nd intron of the MET gene, rs10243024, and platelet aggregation that reached GWAS significance (meta-analysis p-value = 3.61 × 10−8) in Caucasians. This SNP was also significantly associated with platelet aggregation in AA (meta-analysis p-value = 0.03). In both ethnicities, the presence of minor allele was associated with increased maximal aggregation and slope and decreased lag-time (table). This SNP explained up to 2.5% and 0.4% of phenotypic variance in Caucasians and AA respectively. MET receptor activation has been implicated in both platelet function and tumor metastasis, and its ligand, hepatocyte growth factor, is known to cause platelet activation. By using meta-analysis to combine two closely related platelet phenotypes, we have identified an association between variation at rs10243024 of the MET gene and collagen-induced platelet activation. The mechanistic basis for this association requires further study and may have clinical implications for both thrombosis and tumor metastasis.
- © 2010 by American Heart Association, Inc.