Genome-wide association study of PR interval

被引：329

作者：

Pfeufer, Arne ^{[1
,2
]}

van Noord, Charlotte ^{[3
,4
,5
]}

Marciante, Kristin D.

Arking, Dan E. ^{[7
]}

Larson, Martin G. ^{[8
,9
]}

Smith, Albert Vernon ^{[10
]}

Tarasov, Kirill V. ^{[11
,12
]}

Mueller, Martina ^{[13
,14
]}

Sotoodehnia, Nona ^{[6
]}

Sinner, Moritz F. ^{[14
]}

Verwoert, Germaine C. ^{[3
,15
]}

Li, Man ^{[16
]}

Kao, W. H. Linda ^{[16
]}

Koettgen, Anna ^{[16
]}

Coresh, Josef ^{[16
]}

Bis, Joshua C.

Psaty, Bruce M. ^{[17
,18
,19
]}

Rice, Kenneth ^{[20
]}

Rotter, Jerome I. ^{[21
]}

Rivadeneira, Fernando ^{[3
,15
]}

Hofman, Albert ^{[3
]}

Kors, Jan A. ^{[22
]}

Stricker, Bruno H. C. ^{[3
,15
,23
]}

Uitterlinden, Andre G. ^{[3
,15
]}

van Duijn, Cornelia M. ^{[3
]}

Beckmann, Britt M. ^{[14
]}

Sauter, Wiebke ^{[13
]}

Gieger, Christian ^{[13
]}

Lubitz, Steven A. ^{[24
,25
]}

Newton-Cheh, Christopher ^{[25
,26
,27
]}

Wang, Thomas J. ^{[9
,25
,27
]}

Magnani, Jared W.

Schnabel, Renate B. ^{[9
,28
]}

Chung, Mina K. ^{[29
,30
]}

Barnard, John ^{[29
,30
]}

Smith, Jonathan D. ^{[29
,30
]}

Van Wagoner, David R. ^{[29
,30
]}

Vasan, Ramachandran S. ^{[9
]}

Aspelund, Thor ^{[10
,31
]}

Eiriksdottir, Gudny ^{[10
]}

Harris, Tamara B. ^{[32
]}

Launer, Lenore J. ^{[32
]}

Najjar, Samer S. ^{[11
]}

Lakatta, Edward ^{[11
]}

Schlessinger, David ^{[12
]}

Uda, Manuela ^{[33
]}

Abecasis, Goncalo R. ^{[34
]}

Mueller-Myhsok, Bertram ^{[35
]}

Ehret, Georg B. ^{[7
]}

Boerwinkle, Eric ^{[36
,37
]}

机构：

[1] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80804 Munich, Germany

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

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

[4] Dutch Med Evaluat Board, The Hague, Netherlands

[5] Netherlands Consortium Healthy Aging Leiden, Leiden, Netherlands

[6] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA

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

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

[9] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA

[10] Heart Prevent Clin & Res Inst, Iceland Heart Assoc, Kopavogur, Iceland

[11] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA

[12] NIA, Genet Lab, Baltimore, MD 21224 USA

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

[14] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-80804 Munich, Germany

[15] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[16] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

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

[18] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[19] Grp Hlth Res Inst, Seattle, WA USA

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

[21] Cedars Sinai Med Ctr, Dept Common Dis Genet Program, Inst Med Genet, W Hollywood, CA USA

[22] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands

[23] Inspectorate Hlth Care, The Hague, Netherlands

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

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

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

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

[28] Johannes Gutenberg Univ Mainz, Med Clin Cardiol 2, Mainz, Germany

[29] Cleveland Clin, Heart & Vasc Res Inst, Cleveland, OH 44106 USA

[30] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA

[31] Univ Iceland, Heart Prevent Clin & Res Inst, Reykjavik, Iceland

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

[33] CNR, Ist Neurogenet Neurofarmacol, Cagliari, Italy

[34] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[35] Max Planck Inst Psychiat, D-80804 Munich, Germany

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

[37] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA

[38] Johns Hopkins Univ, Dept Med, Baltimore, MD USA

[39] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr EPICARE,Med Ctr, Winston Salem, NC 27109 USA

[40] Helmholtz Ctr, Inst Biol & Med Imaging, Munich, Germany

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

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

[43] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA

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

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

[46] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol & Prevent Med Div,Evans Dept Med, Boston, MA 02118 USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 02期

基金：

美国国家卫生研究院;

关键词：

ATRIAL-FIBRILLATION; COMMON VARIANTS; SODIUM-CHANNEL; HEART-RATE; ATHEROSCLEROSIS RISK; NATIONAL HEART; SYSTEM; DESIGN; INDIVIDUALS; VARIABILITY;

D O I：

10.1038/ng.517

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-nalysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX25 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

引用

页码：153 / U89

页数：9

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