Genome-wide meta-analyses identifies 7 loci associated with platelet aggregation in response to agonists

National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, USA.
Nature Genetics (Impact Factor: 29.35). 07/2010; 42(7):608-13. DOI: 10.1038/ng.604
Source: PubMed


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.

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Available from: Christopher J O'Donnell, Jun 09, 2014
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    • "Nonetheless, an understanding of the responsible genes and underlying mechanisms remains limited to date. In this regard, genome wide association studies (GWAS) have identified loci associated with platelet number, platelet volume and ex vivo platelet aggregation [4,5], but the effect sizes have been quite small. Furthermore, most of the identified loci are not in protein-coding genomic regions. "
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    • "Concludingly, IRAG prevented arterial thrombosis (Antl et al., 2007). Recently, it was reported that IRAG is one of seven proteins which exhibited a polymorphism which was associated with enhanced platelet aggregability known to be a major factor for the incidence of cardiovascular diseases (Johnson et al., 2010). A recent study showed that IRAG might be involved in the activation and attachment of osteoclasts (Yaroslavskiy et al., 2010). "

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