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

Author:
  • Anne M. Butler
  • Xiaoyan Yin
  • Daniel S. Evans
  • Michael A. Nalls
  • Erin N. Smith
  • Toshiko Tanaka
  • Guo Li
  • Sarah G. Buxbaum
  • Eric A. Whitsel
  • Alvaro Alonso
  • Dan E. Arking
  • Emelia J. Benjamin
  • Gerald S. Berenson
  • Josh C. Bis
  • Wei Chen
  • Rajat Deo
  • Patrick T. Ellinor
  • Susan R. Heckbert
  • Gerardo Heiss
  • Wen-Chi Hsueh
  • Brendan J. Keating
  • Kathleen F. Kerr
  • Yun Li
  • Marian C. Limacher
  • Yongmei Liu
  • Steven A. Lubitz
  • Kristin D. Marciante
  • Reena Mehra
  • Yan A. Meng
  • Anne B. Newman
  • Christopher Newton-Cheh
  • Kari E. North
  • Cameron D. Palmer
  • Bruce M. Psaty
  • P. Miguel Quibrera
  • Susan Redline
  • Alex P. Reiner
  • Jerome I. Rotter
  • Renate B. Schnabel
  • Nicholas J. Schork
  • Andrew B. Singleton
  • Gustav Smith
  • Elsayed Z. Soliman
  • Sathanur R. Srinivasan
  • Zhu-ming Zhang
  • Alan B. Zonderman
  • Luigi Ferrucci
  • Sarah S. Murray
  • Michele K. Evans
  • Nona Sotoodehnia
  • Jared W. Magnani
  • Christy L. Avery
Publishing year: 2012
Language: English
Pages: 639-646
Publication/Series: Circulation: Cardiovascular Genetics
Volume: 5
Issue: 6
Document type: Journal article
Publisher: American Heart Association

Abstract english

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.)

Keywords

  • Cardiac and Cardiovascular Systems
  • electrocardiography
  • epidemiology
  • genome-wide association study
  • PR
  • interval
  • single-nucleotide polymorphism genetics

Other

Published
  • ISSN: 1942-325X
E-mail: gustav [dot] smith [at] med [dot] lu [dot] se

Associate professor

Cardiology

+46 46 17 26 33

D1232C

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Research project participant

Cardiovascular Epigenetics

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Research project participant

Heart Failure and Mechanical Support

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Project manager

Molecular Epidemiology and Cardiology

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