Abstract 16386: Genome-Wide Association Study of Native Platelet Function in African Americans
Background: We have previously shown that platelet aggregation, an essential component of pathogenesis of acute coronary syndromes, has higher heritability in African Americans than Caucasians. However, a genome-wide association study of native platelet function in African Americans has not been reported.
Methods: Platelet-rich plasma (PRP) was isolated from blood samples obtained from the discovery (GeneSTAR, N=835) and replication (Platelet Genes and Physiology Study, N=119) cohorts. Optical aggregation was used to measure maximal aggregation in PRP after samples were stimulated with arachidonic acid, collagen, ADP, or epinephrine. For each cohort, age- and sex-adjusted linear mixed models were used to test for association between each SNP and each phenotype under an additive model. Genotyping was conducted with Illumina 1M arrays.
Results: Of the 117 SNPs that were significant (P< 5 x 10-8) in the discovery sample, 50 SNPs in 4 regions were also significant in the replication sample (Table). Among the replicated SNPs, a previously reported SNP in European Americans, rs12041331, in the PEAR1 gene was associated with ADP- and epinephrine-mediated aggregation. 47 SNPs in the 17q21.31 region, in one LD block, were associated with collagen-mediated aggregation.
Conclusions: In this first GWAS of native agonist-mediated platelet aggregation in African Americans, we have discovered, and replicated in an independent sample, 4 regions that are associated with platelet aggregation. Several genes in the identified regions are expressed in platelets and further study of these genes may provide novel insights in platelet biology.
- © 2011 by American Heart Association, Inc.