Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists

Abstract

Platelet function mediates both beneficial and harmful effects on human health, but few genes are known to contribute to variability in this process. We tested association of 2.5 million SNPs with platelet aggregation responses to three agonists (ADP, epinephrine and collagen) in two cohorts of European ancestry (N 2,753 in the Framingham Heart Study, N 1,238 in the Genetic Study of Atherosclerosis Risk). We identified associations of seven loci with platelet aggregation near or within GP6 (P = 4.6 × 10 13), PEAR1 (P = 3.4 × 10-12), ADRA2A (P = 3.3 × 10 11), PIK3CG (P = 3.1 × 10-9), JMJD1C (P = 1.6 × 10-8), MRVI1 (P = 2.0 × 10-8) and SHH (P = 4.5 × 10 8). Six of these loci replicated at P 0.05 in an additional African-American cohort (N 840 in the Genetic Study of Atherosclerosis Risk). These results provide insights into platelet aggregation pathways and may suggest new antiplatelet therapeutic targets. © 2010 Nature America, Inc. All rights reserved.