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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/35452
Title: Genome-wide association study of platelet aggregation in African Americans
Authors: Rehan Qayyum
Lewis C. Becker
Diane M. Becker
Nauder Faraday
Lisa R. Yanek
Suzanne M. Leal
Chad Shaw
Rasika Mathias
Bhoom Suktitipat
Paul F. Bray
The Johns Hopkins School of Medicine
University of Tennessee College of Medicine
Baylor College of Medicine
Mahidol University
Jefferson Medical College
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 30-May-2015
Citation: BMC Genetics. Vol.16, No.1 (2015)
Abstract: © Qayyum et al.; licensee BioMed Central. Background: We have previously shown that platelet aggregation has higher heritability in African Americans than European Americans. However, a genome-wide association study (GWAS) of platelet aggregation in African Americans has not been reported. We measured platelet aggregation in response to arachidonic acid, ADP, collagen, or epinephrine by optical aggregometry. The discovery cohort was 825 African Americans from the GeneSTAR study. Two replication cohorts were used: 119 African Americans from the Platelet Genes and Physiology Study and 1221 European Americans from GeneSTAR. Genotyping was conducted with Illumina 1 M arrays. 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. Results: Six SNPs were significantly associated with platelet aggregation (P < 5×10<sup>-8</sup>) in the discovery sample. Of these, three SNPs in three different loci were confirmed: 1) rs12041331, in PEAR1 (platelet endothelial aggregation receptor 1), replicated in both African and European Americans for collagen- and epinephrine-induced aggregation, and in European Americans for ADP-induced aggregation; 2) rs11202221, in BMPR1A (bone morphogenetic protein receptor type1A), replicated in African Americans for ADP-induced aggregation; and 3) rs6566765 replicated in European Americans for ADP-induced aggregation. The rs11202221 and rs6566765 associations with agonist-induced platelet aggregation are novel. Conclusions: In this first GWAS of agonist-induced platelet aggregation in African Americans, we discovered and replicated, novel associations of two variants with ADP-induced aggregation, and confirmed the association of a PEAR1 variant with multi-agonist-induced aggregation. Further study of these genes may provide novel insights into platelet biology.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84930662804&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/35452
ISSN: 14712156
Appears in Collections:Scopus 2011-2015

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