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

被引：220

作者：

Johnson, Andrew D. ^{[1
,2
]}

Yanek, Lisa R. ^{[3
]}

Chen, Ming-Huei ^{[1
,4
]}

Faraday, Nauder ^{[5
]}

Larson, Martin G. ^{[1
,6
]}

Tofler, Geoffrey ^{[7
]}

Lin, Shiow J. ^{[8
]}

Kraja, Aldi T. ^{[8
]}

Province, Michael A. ^{[8
]}

Yang, Qiong ^{[1
,9
]}

Becker, Diane M. ^{[3
]}

O'Donnell, Christopher J. ^{[1
,2
,10
]}

Becker, Lewis C. ^{[3
]}

机构：

[1] NHLBI, Framingham Heart Study, Framingham, MA USA

[2] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[4] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[5] Johns Hopkins Univ, Sch Med, Dept Anesthesia & Crit Care Med, Baltimore, MD USA

[6] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[7] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia

[8] Washington Univ Med, Div Stat Genom, St Louis, MO USA

[9] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[10] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 07期

关键词：

GLYCOPROTEIN-VI; RECEPTOR; PROTEIN; GENE; EXPRESSION; MOLECULE; VARIANT; RESPONSIVENESS; POLYMORPHISMS; HEMOSTASIS;

D O I：

10.1038/ng.604

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：608 / U186

页数：8

共 49 条

[1] IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation [J].

Antl, Melanie ;

von Bruehl, Marie-Luise ;

Eiglsperger, Christina ;

Werner, Matthias ;

Konrad, Ildiko ;

Kocher, Thomas ;

Wilm, Matthias ;

Hofmann, Franz ;

Massberg, Steffen ;

Schlossmann, Jens .

BLOOD, 2007, 109 (02) :552-559

[2] Sex differences in platelet reactivity and response to low-dose aspirin therapy [J].

Becker, DM ;

Segal, J ;

Vaidya, D ;

Yanek, LR ;

Herrera-Galeano, JE ;

Bray, PF ;

Moy, TF ;

Becker, LC ;

Faraday, N .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 295 (12) :1420-1427

[3] Gene variants associated with deep vein thrombosis [J].

Bezemer, Irene D. ;

Bare, Lance A. ;

Doggen, Carine J. M. ;

Arellano, Andre R. ;

Tong, Carmen ;

Rowland, Charles M. ;

Catanese, Joseph ;

Young, Bradford A. ;

Reitsma, Pieter H. ;

Devlin, James J. ;

Rosendaal, Frits R. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 299 (11) :1306-1314

[4] Heritability of platelet function in families with premature coronary artery disease [J].

Bray, P. F. ;

Mathias, R. A. ;

Faraday, N. ;

Yanek, L. R. ;

Fallin, M. D. ;

Herrera-Galean, J. E. ;

Wilson, A. F. ;

Beckeri, L. C. ;

Becker, D. M. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2007, 5 (08) :1617-1623

[5] Genetic evidence for a predominant role of PI3Kβ catalytic activity in ITAM- and integrin-mediated signaling in platelets [J].

Canobbio, Ilaria ;

Stefanini, Lucia ;

Cipolla, Lina ;

Ciraolo, Elisa ;

Gruppi, Cristian ;

Balduini, Cesare ;

Hirsch, Emilio ;

Torti, Mauro .

BLOOD, 2009, 114 (10) :2193-2196

[6] Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens [J].

Carmen Martinez, Maria ;

Larbret, Frederic ;

Zobairi, Fatiha ;

Coulombe, Josee ;

Debili, Najet ;

Vainchenker, William ;

Ruat, Martial ;

Freyssinet, Jean-Marie .

BLOOD, 2006, 108 (09) :3012-3020

[7] GWAF: an R package for genome-wide association analyses with family data [J].

Chen, Ming-Huei ;

Yang, Qiong .

BIOINFORMATICS, 2010, 26 (04) :580-581

[8] Rap1b is required for normal platelet function and hemostasis in mice [J].

Chrzanowska-Wodnicka, M ;

Smyth, SS ;

Schoenwaelder, SM ;

Fischer, TH ;

White, GC .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (03) :680-687

[9] Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction [J].

Croft, SA ;

Samani, NJ ;

Hampton, KK ;

Steeds, RP ;

Channer, KS ;

Daly, ME .

CIRCULATION, 2001, 104 (13) :1459-1463

[10] Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands [J].

Ellies, LG ;

Ditto, D ;

Levy, GG ;

Wahrenbrock, M ;

Ginsburg, D ;

Varki, A ;

Le, DT ;

Marth, JD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (15) :10042-10047

← 1 2 3 4 5 →