Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts

被引：36

作者：

Butler, Anne M. ^{[1
,9
]}

Yin, Xiaoyan ^{[6
,7
]}

Evans, Daniel S. ^{[8
]}

Nalls, Michael A.

Smith, Erin N. ^{[11
,12
]}

Tanaka, Toshiko ^{[10
]}

Li, Guo ^{[13
]}

Buxbaum, Sarah G. ^{[17
,18
]}

Whitsel, Eric A. ^{[1
,2
]}

Alonso, Alvaro ^{[19
]}

Arking, Dan E. ^{[20
]}

Benjamin, Emelia J. ^{[6
,7
,22
,23
]}

Berenson, Gerald S. ^{[24
]}

Bis, Josh C. ^{[13
]}

Chen, Wei ^{[24
]}

Deo, Rajat ^{[25
]}

Ellinor, Patrick T. ^{[26
,27
,28
]}

Heckbert, Susan R. ^{[13
]}

Heiss, Gerardo ^{[1
]}

Hsueh, Wen-Chi ^{[30
]}

Keating, Brendan J. ^{[14
,31
]}

Kerr, Kathleen F. ^{[15
]}

Li, Yun

Limacher, Marian C. ^{[32
]}

Liu, Yongmei ^{[3
,4
,33
]}

Lubitz, Steven A. ^{[26
,27
]}

Marciante, Kristin D. ^{[13
]}

Mehra, Reena ^{[34
]}

Meng, Yan A. ^{[35
]}

Newman, Anne B. ^{[36
]}

Newton-Cheh, Christopher ^{[26
,27
,29
,35
]}

North, Kari E. ^{[1
,5
]}

Palmer, Cameron D. ^{[35
]}

Psaty, Bruce M. ^{[13
,16
,37
]}

Quibrera, P. Miguel ^{[1
]}

Redline, Susan ^{[14
,38
]}

Reiner, Alex P.

Rotter, Jerome I. ^{[39
]}

Schnabel, Renate B. ^{[40
]}

Schork, Nicholas J. ^{[13
,41
,42
]}

Singleton, Andrew B. ^{[44
]}

Smith, J. Gustav ^{[43
]}

Soliman, Elsayed Z. ^{[33
]}

Srinivasan, Sathanur R. ^{[24
]}

Zhang, Zhu-ming ^{[33
]}

Zonderman, Alan B.

Ferrucci, Luigi ^{[10
]}

Murray, Sarah S. ^{[41
,45
]}

Evans, Michele K. ^{[9
,10
]}

Sotoodehnia, Nona

机构：

[1] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA

[2] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27514 USA

[3] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA

[4] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27514 USA

[5] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA

[6] NHLBI, Framingham, MA USA

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

[8] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA

[9] NIA, Neurogenet Lab, Bethesda, MD 20892 USA

[10] NIA, Clin Res Branch, Bethesda, MD 20892 USA

[11] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[12] Univ Calif San Diego, Sch Med, Rady Childrens Hosp, La Jolla, CA 92093 USA

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

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

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

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

[17] Jackson State Univ, Jackson Heart Study, Jackson, MS USA

[18] Jackson State Univ, Sch Hlth Sci, Jackson, MS USA

[19] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA

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

[21] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA

[22] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA

[23] Boston Univ, Sect Prevent Med, Boston, MA 02215 USA

[24] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA

[25] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA

[26] MGH, Cardiovasc Res Ctr, Charlestown, MA USA

[27] Harvard Univ, Sch Med, Charlestown, MA USA

[28] MGH, Ctr Human Genet Res, Cardiac Arrhythmia Serv, Boston, MA USA

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

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

[31] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA

[32] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA

[33] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA

[34] Case Western Sch Med, Dept Med, Cleveland, OH USA

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

[36] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA

[37] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA

[38] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Sleep Med, Boston, MA 02115 USA

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

[40] Univ Med Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany

[41] Scripps Translat Sci Inst, La Jolla, CA USA

[42] Scripps Res Inst, La Jolla, CA 92037 USA

[43] Lund Univ, Dept Cardiol, Fac Med, Lund, Sweden

[44] NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA

[45] Scripps Hlth, La Jolla, CA USA

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2012年 / 5卷 / 06期

关键词：

electrocardiography; epidemiology; genome-wide association study; PR interval; single-nucleotide polymorphism genetics; COMMON VARIANTS; ATRIAL-FIBRILLATION; HEART-RATE; METAANALYSIS; DURATION; RISK; QRS; PREDICTORS; MUTATION; MODULATE;

D O I：

10.1161/CIRCGENETICS.112.963991

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)

引用

页码：639 / 646

页数：8

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