@article{46fa35530d4a444284b92d6e3d3bd816,
title = "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.",
author = "Johnson, {Andrew D.} and Yanek, {Lisa R.} and Chen, {Ming Huei} and Nauder Faraday and Larson, {Martin G.} and Geoffrey Tofler and Lin, {Shiow J.} and Kraja, {Aldi T.} and Province, {Michael A.} and Qiong Yang and Becker, {Diane M.} and O'Donnell, {Christopher J.} and Becker, {Lewis C.}",
note = "Funding Information: This work was supported by the US National Heart, Lung, and Blood Institute{\textquoteright}s Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This work was supported by the National Heart, Lung, and Blood Institute through the PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01) consortia, and through R01-HL-48157. This research was conducted in part using the resources of the Johns Hopkins General Clinical Research Center, funded through the National Center for Research Resources, M01-RR000052 and the Washington University DSG cluster. We thank G. Ehret and S. Ganesh for providing R code that was modified to generate plots displayed in Figures 1 and 2 and Supplementary Figure 2.",
year = "2010",
month = jul,
doi = "10.1038/ng.604",
language = "English",
volume = "42",
pages = "608--613",
journal = "Nature Genetics",
issn = "1061-4036",
number = "7",
}