A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

被引：553

作者：

Peden, John F. ^{[1
,2
]}

Hopewell, Jemma C. ^{[3
]}

Saleheen, Danish ^{[4
,5
]}

Chambers, John C. ^{[6
,7
]}

Hager, Jorg ^{[8
]}

Soranzo, Nicole ^{[9
]}

Collins, Rory ^{[3
]}

Danesh, John ^{[5
]}

Elliott, Paul ^{[6
,10
]}

Farrall, Martin ^{[1
,2
]}

Stirrups, Kathy ^{[9
]}

Zhang, Weihua ^{[6
,7
]}

Hamsten, Anders ^{[11
,12
]}

Parish, Sarah ^{[3
]}

Lathrop, Mark ^{[8
]}

Watkins, Hugh ^{[1
,2
]}

Clarke, Robert ^{[3
]}

Deloukas, Panos ^{[9
]}

Kooner, Jaspal S. ^{[7
,13
]}

Goel, Anuj ^{[1
,2
]}

Ongen, Halit ^{[1
,2
]}

Strawbridge, Rona J. ^{[11
,12
]}

Heath, Simon ^{[8
]}

Malarstig, Anders ^{[11
,12
]}

Helgadottir, Anna ^{[1
,2
]}

Ohrvik, John ^{[11
,12
]}

Murtaza, Muhammed ^{[9
]}

Potter, Simon ^{[9
]}

Hunt, Sarah E. ^{[9
]}

Delepine, Marc ^{[8
]}

Jalilzadeh, Shapour ^{[1
,2
]}

Axelsson, Tomas ^{[14
]}

Syvanen, Ann-Christine ^{[14
]}

Gwilliam, Rhian ^{[9
]}

Bumpstead, Suzannah ^{[9
]}

Gray, Emma ^{[9
]}

Edkins, Sarah ^{[9
]}

Folkersen, Lasse ^{[11
,12
]}

Kyriakou, Theodosios ^{[1
,2
]}

Franco-Cereceda, Anders ^{[15
]}

Gabrielsen, Anders ^{[16
]}

Seedorf, Udo ^{[17
]}

Eriksson, Per ^{[11
,12
]}

Offer, Alison ^{[3
]}

Bowman, Louise ^{[3
]}

Sleight, Peter ^{[2
]}

Armitage, Jane ^{[3
]}

Peto, Richard ^{[3
]}

Abecasis, Goncalo ^{[18
]}

Ahmed, Nabeel ^{[19
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England

[2] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England

[3] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 9DU, England

[4] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan

[5] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England

[6] Univ London Imperial Coll Sci Technol & Med, London, England

[7] Ealing Hosp Natl Hlth Serv NHS Trust, Southall, Middx, England

[8] CEA, Genom Inst, Ctr Natl Genotypage, Evry, France

[9] Wellcome Trust Sanger Inst, Hinxton, England

[10] Univ London Imperial Coll Sci Technol & Med, Med Res Council Hlth Protect Agcy MRC HPA, Ctr Environm & Hlth, London, England

[11] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden

[12] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden

[13] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

[14] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[15] Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Thorac Surg Unit, Stockholm, Sweden

[16] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden

[17] Univ Munster, Leibniz Inst Arterioskleroseforsch, Gesell Arterioskleroseforsch eV, Munster, Germany

[18] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[19] Ealing Hosp NHS Trust, Southall, Middx, England

[20] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[21] Univ Oxford, Dept Stat, Oxford OX3 9DU, England

[22] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 9DU, England

[23] Churchill Hosp, Oxford Natl Inst Hlth Res NIHR Biomed Res Ctr, Headington, England

[24] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England

[25] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England

[26] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden

[27] Cardiovasc Drug Res Dept Med, Solna, Sweden

[28] AstraZeneca, Cardiovasc & Gastrointestinal Innovat Med, Global Res & Dev, Sodertalje, Sweden

[29] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy

[30] Consorzio Mario Negri Sud, Chieti, Italy

[31] Univ Surrey, Fac Hlth & Med Sci, Div Biochem Sci, Guildford, England

[32] Punjab Inst Cardiol, Dept Cardiol, Lahore, Pakistan

[33] Natl Inst Cardiovasc Dis, Dept Cardiol, Karachi, Pakistan

[34] Karachi Inst Heart Dis, Dept Cardiol, Fed B Area, Karachi, Pakistan

[35] Ch Pervaiz Elahi Inst Cardiol, Dept Cardiol, Multan, Pakistan

[36] Red Crescent Inst Cardiol, Dept Cardiol, Hyderabad, Andhra Pradesh, Pakistan

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

[38] Univ Helsinki, Cent Hosp, Div Cardiol, Helsinki, Finland

[39] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[40] Univ Cent Hosp, Cardiovasc Lab, Helsinki, Finland

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

[42] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[43] Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, S-10401 Stockholm, Sweden

[44] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Lab Clin Epidemiol Cardiovasc Dis, I-66030 Santa Maria Imbaro, Italy

[45] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands

[46] Harokopio Univ, Dept Dietet Nutr, Athens, Greece

[47] McGill Univ, Dept Med, Montreal, PQ, Canada

[48] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[49] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada

[50] McMaster Univ, Dept Med, Hamilton, ON, Canada

来源：

NATURE GENETICS | 2011年 / 43卷 / 04期

基金：

英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会; 瑞典研究理事会;

关键词：

MYOCARDIAL-INFARCTION; CELL MIGRATION; HEART-DISEASE; RISK; SUSCEPTIBILITY; GENE; METAANALYSIS; EXPRESSION;

D O I：

10.1038/ng.782

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.

引用

页码：339 / U89

页数：8

共 35 条

[1] Myocardial expression, signaling, and function of GPR22: a protective role for an orphan G protein-coupled receptor [J].

Adams, John W. ;

Wang, Jianming ;

Davis, James R. ;

Liaw, Chen ;

Gaidarov, Ibragim ;

Gatlin, Joel ;

Dalton, Nancy D. ;

Gu, Yusu ;

Ross, John, Jr. ;

Behan, Dominic ;

Chien, Ken ;

Connolly, Daniel .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2008, 295 (02) :H509-H521

[2] Lipid phosphate phosphatases and signaling [J].

Brindley, David N. ;

Pilquil, Carlos .

JOURNAL OF LIPID RESEARCH, 2009, 50 :S225-S230

[3] Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p [J].

Broadbent, Helen M. ;

Peden, John F. ;

Lorkowski, Stefan ;

Goel, Anuj ;

Ongen, Halit ;

Green, Fiona ;

Clarke, Robert ;

Collins, Rory ;

Franzosi, Maria Grazia ;

Tognoni, Gianni ;

Seedorf, Udo ;

Rust, Stephan ;

Eriksson, Per ;

Hamsten, Anders ;

Farrall, Martin ;

Watkins, Hugh .

HUMAN MOLECULAR GENETICS, 2008, 17 (06) :806-814

[4] Common genetic variation near MC4R is associated with waist circumference and insulin resistance [J].

Chambers, John C. ;

Elliott, Paul ;

Zabaneh, Delilah ;

Zhang, Weihua ;

Li, Yun ;

Froguel, Philippe ;

Balding, David ;

Scott, James ;

Kooner, Jaspal S. .

NATURE GENETICS, 2008, 40 (06) :716-718

[5] Lymphotoxin-α gene and risk of myocardial infarction in 6,928 cases and 2,712 controls in the ISIS case-control study [J].

Clarke, Robert ;

Xu, Peng ;

Bennett, Derrick ;

Lewington, Sarah ;

Zondervan, Krina ;

Parish, Sarah ;

Palmer, Alison ;

Clark, Sarah ;

Cardon, Lon ;

Peto, Richard ;

Lathrop, Mark ;

Collins, Rory .

PLOS GENETICS, 2006, 2 (07) :990-996

[6]

Collins R, 2002, LANCET, V360, P7, DOI 10.1016/S0140-6736(02)09327-3

[7] Genome-wide association study identifies a new locus for coronary artery disease on chromosome 10p11.23 [J].

Erdmann, Jeanette ;

Willenborg, Christina ;

Nahrstaedt, Janja ;

Preuss, Michael ;

Koenig, Inke R. ;

Baumert, Jens ;

Linsel-Nitschke, Patrick ;

Gieger, Christian ;

Tennstedt, Stephanie ;

Belcredi, Petra ;

Aherrahrou, Zouhair ;

Klopp, Norman ;

Loley, Christina ;

Stark, Klaus ;

Hengstenberg, Christian ;

Bruse, Petra ;

Freyer, Jennifer ;

Wagner, Arnika K. ;

Medack, Anja ;

Lieb, Wolfgang ;

Grosshennig, Anika ;

Sager, Hendrik B. ;

Reinhardt, Adrian ;

Schaefer, Arne ;

Schreiber, Stefan ;

El Mokhtari, Nour Eddine ;

Raaz-Schrauder, Dorette ;

Illig, Thomas ;

Garlichs, Christoph D. ;

Ekici, Arif B. ;

Reis, Andre ;

Schrezenmeir, Juergen ;

Rubin, Diana ;

Ziegler, Andreas ;

Wichmann, H. -E. ;

Doering, Angela ;

Meisinger, Christa ;

Meitinger, Thomas ;

Peters, Annette ;

Schunkert, Heribert .

EUROPEAN HEART JOURNAL, 2011, 32 (02) :158-168

[8] New susceptibility locus for coronary artery disease on chromosome 3q22.3 [J].

Erdmann, Jeanette ;

Grosshennig, Anika ;

Braund, Peter S. ;

Koenig, Inke R. ;

Hengstenberg, Christian ;

Hall, Alistair S. ;

Linsel-Nitschke, Patrick ;

Kathiresan, Sekar ;

Wright, Ben ;

Tregouet, David-Alexandre ;

Cambien, Francois ;

Bruse, Petra ;

Aherrahrou, Zouhair ;

Wagner, Arnika K. ;

Stark, Klaus ;

Schwartz, Stephen M. ;

Salomaa, Veikko ;

Elosua, Roberto ;

Melander, Olle ;

Voight, Benjamin F. ;

O'Donnell, Christopher J. ;

Peltonen, Leena ;

Siscovick, David S. ;

Altshuler, David ;

Merlini, Piera Angelica ;

Peyvandi, Flora ;

Bernardinelli, Luisa ;

Ardissino, Diego ;

Schillert, Arne ;

Blankenberg, Stefan ;

Zeller, Tanja ;

Wild, Philipp ;

Schwarz, Daniel F. ;

Tiret, Laurence ;

Perret, Claire ;

Schreiber, Stefan ;

El Mokhtari, Nour Eddine ;

Schaefer, Arne ;

Maerz, Winfried ;

Renner, Wilfried ;

Bugert, Peter ;

Klueter, Harald ;

Schrezenmeir, Juergen ;

Rubin, Diana ;

Ball, Stephen G. ;

Balmforth, Anthony J. ;

Wichmann, H-Erich ;

Meitinger, Thomas ;

Fischer, Marcus ;

Meisinger, Christa .

NATURE GENETICS, 2009, 41 (03) :280-282

[9] Association of Genetic Risk Variants With Expression of Proximal Genes Identifies Novel Susceptibility Genes for Cardiovascular Disease [J].

Folkersen, Lasse ;

van't Hooft, Ferdinand ;

Chernogubova, Ekaterina ;

Agardh, Hanna E. ;

Hansson, Goran K. ;

Hedin, Ulf ;

Liska, Jan ;

Syvanen, Ann-Christine ;

Paulssson-Berne, Gabrielle ;

Franco-Cereceda, Anders ;

Hamsten, Anders ;

Gabrielsen, Anders ;

Eriksson, Per .

CIRCULATION-CARDIOVASCULAR GENETICS, 2010, 3 (04) :365-U306

[10] Genome-wide meta-analyses identify multiple loci associated with smoking behavior [J].

Furberg, Helena ;

Kim, YunJung ;

Dackor, Jennifer ;

Boerwinkle, Eric ;

Franceschini, Nora ;

Ardissino, Diego ;

Bernardinelli, Luisa ;

Mannucci, Pier M. ;

Mauri, Francesco ;

Merlini, Piera A. ;

Absher, Devin ;

Assimes, Themistocles L. ;

Fortmann, Stephen P. ;

Iribarren, Carlos ;

Knowles, Joshua W. ;

Quertermous, Thomas ;

Ferrucci, Luigi ;

Tanaka, Toshiko ;

Bis, Joshua C. ;

Furberg, Curt D. ;

Haritunians, Talin ;

McKnight, Barbara ;

Psaty, Bruce M. ;

Taylor, Kent D. ;

Thacker, Evan L. ;

Almgren, Peter ;

Groop, Leif ;

Ladenvall, Claes ;

Boehnke, Michael ;

Jackson, Anne U. ;

Mohlke, Karen L. ;

Stringham, Heather M. ;

Tuomilehto, Jaakko ;

Benjamin, Emelia J. ;

Hwang, Shih-Jen ;

Levy, Daniel ;

Preis, Sarah Rosner ;

Vasan, Ramachandran S. ;

Duan, Jubao ;

Gejman, Pablo V. ;

Levinson, Douglas F. ;

Sanders, Alan R. ;

Shi, Jianxin ;

Lips, Esther H. ;

Mckay, James D. ;

Agudo, Antonio ;

Barzan, Luigi ;

Bencko, Vladimir ;

Benhamou, Simone ;

Castellsague, Xavier .

NATURE GENETICS, 2010, 42 (05) :441-U134

← 1 2 3 4 →