A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans

被引：81

作者：

Qayyum, Rehan ^{[1
]}

Snively, Beverly M. ^{[2
]}

Ziv, Elad ^{[3
]}

Nalls, Michael A. ^{[4
]}

Liu, Yongmei ^{[5
]}

Tang, Weihong ^{[6
]}

Yanek, Lisa R. ^{[1
]}

Lange, Leslie ^{[7
]}

Evans, Michele K. ^{[8
]}

Ganesh, Santhi ^{[9
]}

Austin, Melissa A. ^{[10
]}

Lettre, Guillaume ^{[12
]}

Becker, Diane M. ^{[1
]}

Zonderman, Alan B. ^{[13
]}

Singleton, Andrew B. ^{[4
]}

Harris, Tamara B. ^{[14
]}

Mohler, Emile R. ^{[15
]}

Logsdon, Benjamin A. ^{[11
]}

Kooperberg, Charles ^{[11
]}

Folsom, Aaron R. ^{[6
]}

Wilson, James G. ^{[16
]}

Becker, Lewis C. ^{[1
]}

Reiner, Alexander P. ^{[10
]}

机构：

[1] Johns Hopkins Sch Med, GeneSTAR Res Program, Div Gen Internal Med, Baltimore, MD USA

[2] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

[4] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[5] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA

[6] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[7] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA

[8] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA

[9] Univ Michigan Hlth Syst, Div Cardiol, Ann Arbor, MI USA

[10] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[11] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA

[12] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada

[13] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA

[14] NIA, Lab Epidemiol Demog & Biometry, NIH, Baltimore, MD 21224 USA

[15] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[16] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA

来源：

PLOS GENETICS | 2012年 / 8卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY; GENE-EXPRESSION; CAPPING PROTEIN; POPULATION; ACTIVATION; DISEASE; TRAITS; RISK; DIFFERENTIATION;

D O I：

10.1371/journal.pgen.1002491

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p < 5 x 10(-8) of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1 x 10(-9)), 7q11 (rs13236689, CD36, p = 2.8 x 10(-9)), 10q21 (rs7896518, JMJD1C, p = 2.3 x 10(-1)2), 11q13 (rs477895, BAD, p = 4.9 x 10(-8)), and 20q13 (rs151361, SLMO2, p = 9.4 x 10(-9)). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p, 5610 28, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.

引用

页数：11

共 66 条

[1] Variants in TF and HFE Explain ∼40% of Genetic Variation in Serum-Transferrin Levels [J].

Benyamin, Beben ;

McRae, Allan E. ;

Zhu, Gu ;

Gordon, Scott ;

Henders, Anjali K. ;

Palotie, Aarno ;

Peltonen, Leena ;

Martin, Nicholas G. ;

Montgomery, Grant W. ;

Whitfield, John B. ;

Visscher, Peter M. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (01) :60-65

[2] Analysis of 12,517 inhabitants of a Sardinian geographic isolate reveals that predispositions to thrombocytopenia and thrombocytosis are inherited traits [J].

Biino, Ginevra ;

Balduini, Carlo L. ;

Casula, Laura ;

Cavallo, Piergiorgio ;

Vaccargiu, Simona ;

Parracciani, Debora ;

Serra, Donatella ;

Portas, Laura ;

Murgia, Federico ;

Pirastu, Mario .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (01) :96-101

[3] Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque [J].

Bis, Joshua C. ;

Kavousi, Maryam ;

Franceschini, Nora ;

Isaacs, Aaron ;

Abecasis, Goncalo R. ;

Schminke, Ulf ;

Post, Wendy S. ;

Smith, Albert V. ;

Cupples, L. Adrienne ;

Markus, Hugh S. ;

Schmidt, Reinhold ;

Huffman, Jennifer E. ;

Lehtimaki, Terho ;

Baumert, Jens ;

Muenzel, Thomas ;

Heckbert, Susan R. ;

Dehghan, Abbas ;

North, Kari ;

Oostra, Ben ;

Bevan, Steve ;

Stoegerer, Eva-Maria ;

Hayward, Caroline ;

Raitakari, Olli ;

Meisinger, Christa ;

Schillert, Arne ;

Sanna, Serena ;

Voelzke, Henry ;

Cheng, Yu-Ching ;

Thorsson, Bolli ;

Fox, Caroline S. ;

Rice, Kenneth ;

Rivadeneira, Fernando ;

Nambi, Vijay ;

Halperin, Eran ;

Petrovic, Katja E. ;

Peltonen, Leena ;

Wichmann, H. Erich ;

Schnabel, Renate B. ;

Doerr, Marcus ;

Parsa, Afshin ;

Aspelund, Thor ;

Demissie, Serkalem ;

Kathiresan, Sekar ;

Reilly, Muredach P. ;

Taylor, Kent ;

Uitterlinden, Andre ;

Couper, David J. ;

Sitzer, Matthias ;

Kahonen, Mika ;

Illig, Thomas .

NATURE GENETICS, 2011, 43 (10) :940-U40

[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]

Buckley MF, 2000, THROMB HAEMOSTASIS, V83, P480

[6] Profiling of gene transcripts in human platelets:: An update of the platelet transcriptome [J].

Bugert, P. ;

Klueter, H. .

PLATELETS, 2006, 17 (07) :503-504

[7] Genome-Wide Association Study SNPs in the Human Genome Diversity Project Populations: Does Selection Affect Unlinked SNPs with Shared Trait Associations? [J].

Casto, Amanda M. ;

Feldman, Marcus W. .

PLOS GENETICS, 2011, 7 (01)

[8] Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis [J].

Chasman, Daniel I. ;

Pare, Guillaume ;

Mora, Samia ;

Hopewell, Jemma C. ;

Peloso, Gina ;

Clarke, Robert ;

Cupples, L. Adrienne ;

Hamsten, Anders ;

Kathiresan, Sekar ;

Maelarstig, Anders ;

Ordovas, Jose M. ;

Ripatti, Samuli ;

Parker, Alex N. ;

Miletich, Joseph P. ;

Ridker, Paul M. .

PLOS GENETICS, 2009, 5 (11)

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

Chen, Ming-Huei ;

Yang, Qiong .

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

[10] Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis [J].

Chu, S. G. ;

Becker, R. C. ;

Berger, P. B. ;

Bhatt, D. L. ;

Eikelboom, J. W. ;

Konkle, B. ;

Mohler, E. R. ;

Reilly, M. P. ;

Berger, J. S. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2010, 8 (01) :148-156

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