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Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants

Author:
  • R. Deo
  • M. A. Nalls
  • C. L. Avery
  • Gustav Smith
  • D. S. Evans
  • M. F. Keller
  • A. M. Butler
  • S. G. Buxbaum
  • G. Li
  • P. Miguel Quibrera
  • E. N. Smith
  • T. Tanaka
  • E. L. Akylbekova
  • A. Alonso
  • D. E. Arking
  • E. J. Benjamin
  • G. S. Berenson
  • J. C. Bis
  • L. Y. Chen
  • W. Chen
  • S. R. Cummings
  • P. T. Ellinor
  • M. K. Evans
  • L. Ferrucci
  • E. R. Fox
  • S. R. Heckbert
  • G. Heiss
  • W. C. Hsueh
  • K. F. Kerr
  • M. C. Limacher
  • Y. Liu
  • S. A. Lubitz
  • J. W. Magnani
  • R. Mehra
  • G. M. Marcus
  • S. S. Murray
  • A. B. Newman
  • O. Njajou
  • K. E. North
  • D. N. Paltoo
  • B. M. Psaty
  • S. S. Redline
  • A. P. Reiner
  • J. G. Robinson
  • J. I. Rotter
  • T. E. Samdarshi
  • R. B. Schnabel
  • N. J. Schork
  • A. B. Singleton
  • D. Siscovick
  • E. Z. Soliman
  • N. Sotoodehnia
  • S. R. Srinivasan
  • H. A. Taylor
  • M. Trevisan
  • Z. Zhang
  • A. B. Zonderman
  • C. Newton-Cheh
  • E. A. Whitsel
Publishing year: 2013
Language: English
Pages: 401-408
Publication/Series: Heart Rhythm
Volume: 10
Issue: 3
Document type: Journal article
Publisher: Elsevier

Abstract english

BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of singe nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P <= 2.5 x 10(-8)). RESULTS Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Keywords

  • Cardiac and Cardiovascular Systems
  • African Americans
  • Heart rate
  • Singe nucleotide polymorphisms
  • Meta-analysis

Other

Published
  • ISSN: 1547-5271
E-mail: gustav.smith [at] med.lu.se

Associate professor

Cardiology

+46 46 17 26 33

D1232C

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Research project participant

Cardiovascular Epigenetics

32

Research project participant

Heart Failure and Mechanical Support

32

Project manager

Molecular Epidemiology and Cardiology

+46 46 17 26 33

32

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