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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.

Publication ,  Journal Article
Deo, R; Nalls, MA; Avery, CL; Smith, JG; Evans, DS; Keller, MF; Butler, AM; Buxbaum, SG; Li, G; Miguel Quibrera, P; Smith, EN; Tanaka, T ...
Published in: Heart Rhythm
March 2013

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 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.

Duke Scholars

Published In

Heart Rhythm

DOI

EISSN

1556-3871

Publication Date

March 2013

Volume

10

Issue

3

Start / End Page

401 / 408

Location

United States

Related Subject Headings

  • United States
  • Rest
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Heart Rate
  • Genotype
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
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Deo, R., Nalls, M. A., Avery, C. L., Smith, J. G., Evans, D. S., Keller, M. F., … Whitsel, E. A. (2013). 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. Heart Rhythm, 10(3), 401–408. https://doi.org/10.1016/j.hrthm.2012.11.014
Deo, R., M. A. Nalls, C. L. Avery, J. G. Smith, D. S. Evans, M. F. Keller, A. M. Butler, et al. “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.Heart Rhythm 10, no. 3 (March 2013): 401–8. https://doi.org/10.1016/j.hrthm.2012.11.014.
Deo, R., et al. “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.Heart Rhythm, vol. 10, no. 3, Mar. 2013, pp. 401–08. Pubmed, doi:10.1016/j.hrthm.2012.11.014.
Deo R, Nalls MA, Avery CL, Smith JG, Evans DS, Keller MF, Butler AM, Buxbaum SG, Li G, Miguel Quibrera P, Smith EN, Tanaka T, Akylbekova EL, Alonso A, Arking DE, Benjamin EJ, Berenson GS, Bis JC, Chen LY, Chen W, Cummings SR, Ellinor PT, Evans MK, Ferrucci L, Fox ER, Heckbert SR, Heiss G, Hsueh WC, Kerr KF, Limacher MC, Liu Y, Lubitz SA, Magnani JW, Mehra R, Marcus GM, Murray SS, Newman AB, Njajou O, North KE, Paltoo DN, Psaty BM, Redline SS, Reiner AP, Robinson JG, Rotter JI, Samdarshi TE, Schnabel RB, Schork NJ, Singleton AB, Siscovick D, Soliman EZ, Sotoodehnia N, Srinivasan SR, Taylor HA, Trevisan M, Zhang Z, Zonderman AB, Newton-Cheh C, Whitsel EA. 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. Heart Rhythm. 2013 Mar;10(3):401–408.
Journal cover image

Published In

Heart Rhythm

DOI

EISSN

1556-3871

Publication Date

March 2013

Volume

10

Issue

3

Start / End Page

401 / 408

Location

United States

Related Subject Headings

  • United States
  • Rest
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Heart Rate
  • Genotype
  • Genome-Wide Association Study