Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists.
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<or=2,753 in the Framingham Heart Study, N<or=1,238 in the Genetic Study of Atherosclerosis Risk). We identified associations of seven loci with platelet aggregation near or within GP6 (P=4.6x10(-13)), PEAR1 (P=3.4x10(-12)), ADRA2A (P=3.3x10(-11)), PIK3CG (P=3.1x10(-9)), JMJD1C (P=1.6x10(-8)), MRVI1 (P=2.0x10(-8)) and SHH (P=4.5x10(-8)). Six of these loci replicated at P<0.05 in an additional African-American cohort (N<or=840 in the Genetic Study of Atherosclerosis Risk). These results provide insights into platelet aggregation pathways and may suggest new antiplatelet therapeutic targets.
Johnson
Andrew D
AD
National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, USA. johnsonad2@nhlbi.nih.gov
Yanek
Lisa R
LR
Chen
Ming-Huei
MH
Faraday
Nauder
N
Larson
Martin G
MG
Tofler
Geoffrey
G
Lin
Shiow J
SJ
Kraja
Aldi T
AT
Province
Michael A
MA
Yang
Qiong
Q
Becker
Diane M
DM
O'Donnell
Christopher J
CJ
Becker
Lewis C
LC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D015331:Cohort Studies; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
D000316:Adrenergic alpha-Agonists; D000244:Adenosine Diphosphate; D003094:Collagen; D004837:Epinephrine