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

R Deo; J.G Robinson; S.S Murray; M.A Nalls; C.L Avery; J.G 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; S.A Lubitz; J.W Magnani; R Mehra; G.M Marcus; A.B Newman; O Njajou; K.E North; D.N Paltoo; B.M Psaty; S.S Redline; A.P Reiner; 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; Y Liu; E.A Whitsel

doi:10.1016/j.hrthm.2012.11.014

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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

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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

R Deo, J.G Robinson, S.S Murray, M.A Nalls, C.L Avery, J.G Smith, D.S Evans, M.F Keller, A.M Butler, S.G Buxbaum, …

Heart rhythm, Vol.10(3), pp.401-408

03/2013

DOI: 10.1016/j.hrthm.2012.11.014

PMCID: PMC3718037

PMID: 23183192

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Abstract

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 single 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≤2.5×10 −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 = 4.98×10 −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.

African Americans

Heart rate

Single nucleotide polymorphisms

Meta-analysis

Details

Title: Subtitle: 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
Creators: R Deo - Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia, Pennsylvania
J.G Robinson - Department of Epidemiology, University of Iowa, Iowa City, Iowa
S.S Murray - Scripps Translational Science Institute and Scripps Research Institute, La Jolla, California
M.A Nalls - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland
C.L Avery - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina
J.G Smith - Lund University
D.S Evans - California Pacific Medical Center Research Institute, San Francisco, California
M.F Keller - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland
A.M Butler - University of North Carolina at Chapel Hill
S.G Buxbaum - Jackson Heart Study, Jackson State University, Jackson, Mississippi
G Li - University of Washington
P Miguel Quibrera - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
E.N Smith - University of California San Diego
T Tanaka - Clinical Research Branch, National Institute on Aging, Baltimore, Maryland
E.L Akylbekova - Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
A Alonso - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
D.E Arking - McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
E.J Benjamin - NHLBI’s Framingham Study, Framingham, Massachusetts
G.S Berenson - Department of Epidemiology, Tulane University, New Orleans, Louisiana
J.C Bis - Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington
L.Y Chen - University of Minnesota Medical School
W Chen - Tulane University
S.R Cummings - California Pacific Medical Center Research Institute, San Francisco, California
P.T Ellinor - Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
M.K Evans - Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, National Institute of Health, Baltimore, Maryland
L Ferrucci - Clinical Research Branch, National Institute on Aging, National Institute of Health, Baltimore, Maryland
E.R Fox - Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
S.R Heckbert - Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington
G Heiss - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
W.C Hsueh - Department of Medicine, University of California, San Francisco, California
K.F Kerr - Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington
M.C Limacher - Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida
S.A Lubitz - Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
J.W Magnani - Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, Massachusetts
R Mehra - Department of Medicine, Case Western School of Medicine, Cleveland, Ohio
G.M Marcus - Division of Cardiology, Electrophysiology Section, University of California, San Francisco, California
A.B Newman - Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
O Njajou - Institute of Human Genetics, University of California, San Francisco, California
K.E North - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
D.N Paltoo - Office of Science Policy, Office of the Director, National Institutes of Health, Bethesda, Maryland
B.M Psaty - Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington
S.S Redline - Division of Sleep Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
A.P Reiner - Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington
J.I Rotter - Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
T.E Samdarshi - University of Mississippi School of Medicine, Jackson, Mississippi
R.B Schnabel - Department of General and Interventional Cardiology, University Heart Center, Hamburg-Eppendorf, Germany
N.J Schork - Scripps Translational Science Institute and Scripps Research Institute, La Jolla, California
A.B Singleton - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland
D Siscovick - Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington
E.Z Soliman - Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
N Sotoodehnia - Division of Cardiology, University of Washington, Seattle, Washington
S.R Srinivasan - Department of Epidemiology, Tulane University, New Orleans, Louisiana
H.A Taylor - Departments of Medicine, Epidemiology, and Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi
M Trevisan - Sophie Davis School of Biomedical Education, City College of New York, New York, New York
Z Zhang - Epidemiological Cardiology Center (EPICARE), Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
A.B Zonderman - National Institute on Aging, National Institute on Aging, Bethesda, Maryland
C Newton-Cheh - Program for Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, Massachusetts
Y Liu - Wake Forest University
E.A Whitsel - Departments of Epidemiology and Medicine, University of North Carolina, Chapel Hill, North Carolina
Resource Type: Journal article
Publication Details: Heart rhythm, Vol.10(3), pp.401-408
DOI: 10.1016/j.hrthm.2012.11.014
PMID: 23183192
PMCID: PMC3718037
NLM abbreviation: Heart Rhythm
ISSN: 1547-5271
eISSN: 1556-3871
Publisher: Elsevier Inc
Language: English
Date published: 03/2013
Academic Unit: Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9983995037702771

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