A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium

被引：426

作者：

Soranzo, Nicole ^{[1
,2
]}

Spector, Tim D. ^{[2
]}

Mangino, Massimo ^{[2
]}

Kuehnel, Brigitte ^{[3
]}

Rendon, Augusto ^{[4
,5
]}

Teumer, Alexander ^{[6
]}

Willenborg, Christina ^{[7
,8
]}

Wright, Benjamin ^{[9
]}

Chen, Li ^{[10
]}

Li, Mingyao ^{[11
]}

Salo, Perttu ^{[12
,13
]}

Voight, Benjamin F. ^{[14
,15
]}

Burns, Philippa ^{[4
,5
]}

Laskowski, Roman A. ^{[16
]}

Xue, Yali ^{[1
]}

Menzel, Stephan ^{[17
]}

Altshuler, David ^{[14
,15
,18
,19
,20
]}

Bradley, John R. ^{[21
]}

Bumpstead, Suzannah ^{[1
]}

Burnett, Mary-Susan ^{[22
]}

Devaney, Joseph ^{[22
]}

Doering, Angela ^{[3
]}

Elosua, Roberto ^{[23
,24
]}

Epstein, Stephen E. ^{[22
]}

Erber, Wendy ^{[25
]}

Falchi, Mario ^{[2
,26
]}

Garner, Stephen F. ^{[4
,5
]}

Ghori, Mohammed J. R. ^{[1
]}

Goodall, Alison H. ^{[27
]}

Gwilliam, Rhian ^{[1
]}

Hakonarson, Hakon H. ^{[28
]}

Hall, Alistair S. ^{[29
]}

Hammond, Naomi ^{[1
]}

Hengstenberg, Christian ^{[30
]}

Illig, Thomas ^{[3
]}

Koenig, Inke R. ^{[7
]}

Knouff, Christopher W. ^{[31
]}

McPherson, Ruth ^{[10
]}

Melander, Olle ^{[32
]}

Mooser, Vincent ^{[31
]}

Nauck, Matthias ^{[33
]}

Nieminen, Markku S. ^{[34
]}

O'Donnell, Christopher J. ^{[19
,35
,36
]}

Peltonen, Leena ^{[12
,13
]}

Potter, Simon C. ^{[1
]}

Prokisch, Holger ^{[37
,38
]}

Rader, Daniel J. ^{[39
,40
]}

Rice, Catherine M. ^{[1
]}

Roberts, Robert ^{[10
]}

Salomaa, Veikko ^{[12
,13
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton, England

[2] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[3] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[4] Univ Cambridge, Dept Haematol, Cambridge, England

[5] Natl Hlth Serv Blood & Transplant, Cambridge, England

[6] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[7] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany

[8] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany

[9] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England

[10] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada

[11] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[12] Natl Inst Hlth & Welf, Helsinki, Finland

[13] Univ Helsinki, Inst Mol Med, FIN-00014 Helsinki, Finland

[14] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[15] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[16] European Bioinformat Inst, Hinxton, England

[17] Kings Coll London, Dept Haematol, London WC2R 2LS, England

[18] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[19] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[21] Univ Cambridge, Sch Clin Med, Dept Med, Addenbrookes Hosp, Cambridge, England

[22] Washington Hosp Ctr, MedStar Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA

[23] Inst Municipal Invest Med, E-08003 Barcelona, Spain

[24] CIBER Epidemiol & Salud Publ, E-08003 Barcelona, Spain

[25] Cambridge Univ Hosp NHS Fdn Trust, Dept Haematol, Cambridge, England

[26] Univ London Imperial Coll Sci Technol & Med, Sect Genom Med, London, England

[27] Univ Leicester, Glenfield Hosp, Leicester, Leics, England

[28] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[29] Leeds Gen Infirm, BHF Heart Res Ctr, Leeds, W Yorkshire, England

[30] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany

[31] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA

[32] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo Univ Hosp, Malmo, Sweden

[33] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany

[34] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland

[35] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[36] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[37] Tech Univ Munich, Klinikum Rechts Isar, Dept Human Genet, D-8000 Munich, Germany

[38] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[39] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA

[40] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA

[41] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany

[42] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[43] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[44] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany

[45] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[46] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany

[47] Queen Mary Univ London, Inst Cell & Mol Sci, Barts & London Sch Med & Dent, London, England

[48] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

基金：

英国惠康基金; 加拿大健康研究院; 加拿大创新基金会; 美国国家卫生研究院;

关键词：

MEAN PLATELET VOLUME; MYOCARDIAL-INFARCTION; RISK; VARIANTS; DISEASE; GENE; EXPRESSION; MUTATIONS; PROTEIN; DIFFERENTIATION;

D O I：

10.1038/ng.467

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.

引用

页码：1182 / U38

页数：11

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