Multiple Platelet Aggregation Genes Are Identified By Genome-Wide Association Meta-Analyses

Platelet aggregation plays an important role in arterial thrombosis. While a few candidate gene polymorphisms have been previously associated with platelet aggregation, a genome-wide association study (GWAS) has not been reported. We hypothesized that meta-analysis of results from multiple GWAS would discover new genes contributing to aggregation. In two separate GWAS conducted in white participants, the Framingham Heart Study (FHS) Offspring cohort and GeneSTAR (GS), platelet rich plasma (PRP) was isolated from fasting blood samples. Subjects with CAD or anti-coagulant or anti-platelet medication were excluded. PRP samples were treated with varying doses of agonists (collagen, ADP, epinephrine) and lag time, biphasic responses and maximal aggregation were measured. Genotyping was conducted with Affymetrix 500K + 50K MIPs arrays (FHS) and Illumina 1M arrays (GS). After genotyping QC, both cohorts used MACH software to impute 2.54 million common SNPs based on the HapMap. The imputed SNP dosages were used i...