Meta-analysis identifies six new susceptibility loci for atrial fibrillation

被引：461

作者：

Ellinor, Patrick T. ^{[1
,2
,3
,4
]}

Lunetta, Kathryn L. ^{[5
,6
,7
]}

Albert, Christine M. ^{[4
,8
,9
]}

Glazer, Nicole L. ^{[10
]}

Ritchie, Marylyn D. ^{[11
]}

Smith, Albert V. ^{[12
,13
]}

Arking, Dan E. ^{[14
]}

Mueller-Nurasyid, Martina ^{[15
,16
,17
]}

Krijthe, Bouwe P. ^{[18
]}

Lubitz, Steven A. ^{[1
,8
]}

Bis, Joshua C. ^{[10
]}

Chung, Mina K. ^{[19
,20
]}

Doerr, Marcus ^{[21
]}

Ozaki, Kouichi ^{[22
]}

Roberts, Jason D. ^{[23
]}

Smith, J. Gustav ^{[24
,25
]}

Pfeufer, Arne ^{[26
,27
]}

Sinner, Moritz F. ^{[1
,6
,7
,15
]}

Lohman, Kurt ^{[28
]}

Ding, Jingzhong ^{[29
]}

Smith, Nicholas L. ^{[10
,30
,31
,32
]}

Smith, Jonathan D. ^{[19
,33
]}

Rienstra, Michiel ^{[1
,34
]}

Rice, Kenneth M. ^{[35
]}

Van Wagoner, David R. ^{[19
,20
]}

Magnani, Jared W. ^{[6
,7
,36
]}

Wakili, Reza ^{[15
]}

Clauss, Sebastian ^{[15
]}

Rotter, Jerome I. ^{[37
]}

Steinbeck, Gerhard ^{[15
]}

Launer, Lenore J. ^{[38
]}

Davies, Robert W. ^{[39
]}

Borkovich, Matthew ^{[23
]}

Harris, Tamara B. ^{[38
]}

Lin, Honghuang ^{[36
]}

Voelker, Uwe ^{[40
]}

Voelzke, Henry ^{[41
]}

Milan, David J. ^{[1
,2
]}

Hofman, Albert ^{[18
]}

Boerwinkle, Eric ^{[42
]}

Chen, Lin Y. ^{[43
]}

Soliman, Elsayed Z. ^{[44
]}

Voight, Benjamin F. ^{[25
]}

Li, Guo ^{[10
]}

Chakravarti, Aravinda ^{[14
]}

Kubo, Michiaki ^{[45
]}

Tedrow, Usha B. ^{[4
,8
,9
]}

Rose, Lynda M. ^{[8
]}

Ridker, Paul M. ^{[4
,8
,9
]}

Conen, David ^{[46
]}

机构：

[1] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA

[2] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA

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

[4] Harvard Univ, Sch Med, Boston, MA USA

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

[6] NHLBI, Framingham, MA USA

[7] Boston Univ, Framingham Heart Study, Framingham, MA USA

[8] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA

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

[11] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA

[12] Iceland Heart Assoc Res Inst, Kopavogur, Iceland

[13] Univ Iceland, Fac Med, Reykjavik, Iceland

[14] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[15] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany

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

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

[18] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[19] Cleveland Clin, Dept Cardiovasc Med, Inst Heart & Vasc, Cleveland, OH 44106 USA

[20] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA

[21] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany

[22] RIKEN Ctr Genom Med, Lab Cardiovasc Dis, Kanagawa, Japan

[23] Univ Ottawa, Inst Heart, Arrhythmia Res Lab, Ottawa, ON, Canada

[24] Lund Univ, Dept Cardiol, Lund, Sweden

[25] Broad Inst Harvard & MIT, Cambridge, MA USA

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

[27] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany

[28] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA

[29] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA

[30] Dept Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA

[31] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA

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

[33] Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44106 USA

[34] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands

[35] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[36] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA

[37] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[38] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, US NIH, Bethesda, MD 20892 USA

[39] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada

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

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

[42] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[43] Univ Minnesota, Sch Med, Dept Med, Cardiac Arrhythmia Ctr,Cardiovasc Div, Minneapolis, MN 55455 USA

[44] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA

[45] RIKEN Ctr Genom Med, Lab Genotyping Dev, Kanagawa, Japan

[46] Univ Basel Hosp, Dept Med, CH-4031 Basel, Switzerland

[47] RIKEN Ctr Genom Med, Lab Med Informat, Kanagawa, Japan

[48] Tokyo Med & Dent Univ, Med Res Inst, Dept Bioinformat Pharmacol, Tokyo, Japan

[49] Univ Washington, Div Cardiol, Seattle, WA 98195 USA

[50] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 06期

关键词：

GENOME-WIDE ASSOCIATION; COMMON VARIANTS; REPLICATION; CAVEOLIN-1; MUTATIONS; PATIENT; ZFHX3; HEART; RISK; PRX1;

D O I：

10.1038/ng.2261

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

引用

页码：670 / U88

页数：7

共 30 条

[1] Mutations in PDLIM3 and MYOZ1 encoding myocyte Z line proteins are infrequently found in idiopathic dilated cardiomyopathy [J].

Arola, Anita M. ;

Sanchez, Ximena ;

Murphy, Ross T. ;

Hasle, Erika ;

Li, Hua ;

Elliott, Perry M. ;

McKenna, William J. ;

Towbin, Jeffrey A. ;

Bowles, Neil E. .

MOLECULAR GENETICS AND METABOLISM, 2007, 90 (04) :435-440

[2] Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry [J].

Benjamin, Emelia J. ;

Rice, Kenneth M. ;

Arking, Dan E. ;

Pfeufer, Arne ;

van Noord, Charlotte ;

Smith, Albert V. ;

Schnabel, Renate B. ;

Bis, Joshua C. ;

Boerwinkle, Eric ;

Sinner, Moritz F. ;

Dehghan, Abbas ;

Lubitz, Steven A. ;

D'Agostino, Ralph B., Sr. ;

Lumley, Thomas ;

Ehret, Georg B. ;

Heeringa, Jan ;

Aspelund, Thor ;

Newton-Cheh, Christopher ;

Larson, Martin G. ;

Marciante, Kristin D. ;

Soliman, Elsayed Z. ;

Rivadeneira, Fernando ;

Wang, Thomas J. ;

Eiriksdottir, Gudny ;

Levy, Daniel ;

Psaty, Bruce M. ;

Li, Man ;

Chamberlain, Alanna M. ;

Hofman, Albert ;

Vasan, Ramachandran S. ;

Harris, Tamara B. ;

Rotter, Jerome I. ;

Kao, W. H. Linda ;

Agarwal, Sunil K. ;

Stricker, Bruno H. Ch ;

Wang, Ke ;

Launer, Lenore J. ;

Smith, Nicholas L. ;

Chakravarti, Aravinda ;

Uitterlinden, Andre G. ;

Wolf, Philip A. ;

Sotoodehnia, Nona ;

Koettgen, Anna ;

van Duijn, Cornelia M. ;

Meitinger, Thomas ;

Mueller, Martina ;

Perz, Siegfried ;

Steinbeck, Gerhard ;

Wichmann, H-Erich ;

Lunetta, Kathryn L. .

NATURE GENETICS, 2009, 41 (08) :879-881

[3] CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function [J].

Beqqali, Abdelaziz ;

Monshouwer-Kloots, Jantine ;

Monteiro, Rui ;

Welling, Maaike ;

Bakkers, Jeroen ;

Ehler, Elisabeth ;

Verkleij, Arie ;

Mummery, Christine ;

Passier, Robert .

JOURNAL OF CELL SCIENCE, 2010, 123 (07) :1141-1150

[4] Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus [J].

Bergwerff, M ;

Gittenberger-de Groot, AC ;

Wisse, LJ ;

DeRuiter, MC ;

Wessels, A ;

Martin, JF ;

Olson, EN ;

Kern, MJ .

VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 2000, 436 (01) :12-19

[5] Identification of a genetic locus for familial atrial fibrillation [J].

Brugada, R ;

Tapscott, T ;

Czernuszewicz, GZ ;

Marian, AJ ;

Iglesias, A ;

Mont, L ;

Brugada, J ;

Girona, J ;

Domingo, A ;

Bachinski, LL ;

Roberts, R .

NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (13) :905-911

[6] Practical aspects of imputation-driven meta-analysis of genome-wide association studies [J].

de Bakker, Paul I. W. ;

Ferreira, Manuel A. R. ;

Jia, Xiaoming ;

Neale, Benjamin M. ;

Raychaudhuri, Soumya ;

Voight, Benjamin F. .

HUMAN MOLECULAR GENETICS, 2008, 17 :R122-R128

[7] Common variants in KCNN3 are associated with lone atrial fibrillation [J].

Ellinor, Patrick T. ;

Lunetta, Kathryn L. ;

Glazer, Nicole L. ;

Pfeufer, Arne ;

Alonso, Alvaro ;

Chung, Mina K. ;

Sinner, Moritz F. ;

de Bakker, Paul I. W. ;

Mueller, Martina ;

Lubitz, Steven A. ;

Fox, Ervin ;

Darbar, Dawood ;

Smith, Nicholas L. ;

Smith, Jonathan D. ;

Schnabel, Renate B. ;

Soliman, Elsayed Z. ;

Rice, Kenneth M. ;

Van Wagoner, David R. ;

Beckmann, Britt-M ;

van Noord, Charlotte ;

Wang, Ke ;

Ehret, Georg B. ;

Rotter, Jerome I. ;

Hazen, Stanley L. ;

Steinbeck, Gerhard ;

Smith, Albert V. ;

Launer, Lenore J. ;

Harris, Tamara B. ;

Makino, Seiko ;

Nelis, Mari ;

Milan, David J. ;

Perz, Siegfried ;

Esko, Tonu ;

Koettgen, Anna ;

Moebus, Susanne ;

Newton-Cheh, Christopher ;

Li, Man ;

Moehlenkamp, Stefan ;

Wang, Thomas J. ;

Kao, W. H. Linda ;

Vasan, Ramachandran S. ;

Noethen, Markus M. ;

MacRae, Calum A. ;

Stricker, Bruno H. Ch ;

Hofman, Albert ;

Uitterlinden, Andre G. ;

Levy, Daniel ;

Boerwinkle, Eric ;

Metspalu, Andres ;

Topol, Eric J. .

NATURE GENETICS, 2010, 42 (03) :240-U36

[8] Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins [J].

Frey, N ;

Olson, EN .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (16) :13998-14004

[9] ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society [J].

Fuster, Valentin ;

Ryden, Lars E. ;

Cannom, David S. ;

Crijns, Harry J. ;

Curtis, Anne B. ;

Ellenbogen, Kenneth A. ;

Halperin, Jonathan L. ;

Le Heuzey, Jean-Yves ;

Kay, G. Neal ;

Lowe, James E. ;

Olsson, S. Bertil ;

Prystowsky, Eric N. ;

Tamargo, Juan Luis ;

Wann, Samuel .

CIRCULATION, 2006, 114 (07) :E257-E354

[10] The International HapMap Project [J].

Gibbs, RA ;

Belmont, JW ;

Hardenbol, P ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Ch'ang, LY ;

Huang, W ;

Liu, B ;

Shen, Y ;

Tam, PKH ;

Tsui, LC ;

Waye, MMY ;

Wong, JTF ;

Zeng, CQ ;

Zhang, QR ;

Chee, MS ;

Galver, LM ;

Kruglyak, S ;

Murray, SS ;

Oliphant, AR ;

Montpetit, A ;

Hudson, TJ ;

Chagnon, F ;

Ferretti, V ;

Leboeuf, M ;

Phillips, MS ;

Verner, A ;

Kwok, PY ;

Duan, SH ;

Lind, DL ;

Miller, RD ;

Rice, JP ;

Saccone, NL ;

Taillon-Miller, P ;

Xiao, M ;

Nakamura, Y ;

Sekine, A ;

Sorimachi, K ;

Tanaka, T ;

Tanaka, Y ;

Tsunoda, T ;

Yoshino, E ;

Bentley, DR ;

Deloukas, P ;

Hunt, S ;

Powell, D ;

Altshuler, D ;

Gabriel, SB ;

Qiu, RZ .

NATURE, 2003, 426 (6968) :789-796

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