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

Deo, R.; Nalls, M. A.; Avery, C. L.; Smith, Gustav; Evans, D. S.; Keller, M. F.; Butler, A. M.; Buxbaum, S. G.; Li, G.; Quibrera, P. Miguel; Smith, E. N.; Tanaka, T.; Akylbekova, E. L.; Alonso, A.; Arking, D. E.; Benjamin, E. J.; Berenson, G. S.; Bis, J. C.; Chen, L. Y.; Chen, W.; Cummings, S. R.; Ellinor, P. T.; Evans, M. K.; Ferrucci, L.; Fox, E. R.; Heckbert, S. R.; Heiss, G.; Hsueh, W. C.; Kerr, K. F.; Limacher, M. C.; Liu, Y.; Lubitz, S. A.; Magnani, J. W.; Mehra, R.; Marcus, G. M.; Murray, S. S.; Newman, A. B.; Njajou, O.; North, K. E.; Paltoo, D. N.; Psaty, B. M.; Redline, S. S.; Reiner, A. P.; Robinson, J. G.; Rotter, J. I.; Samdarshi, T. E.; Schnabel, R. B.; Schork, N. J.; Singleton, A. B.; Siscovick, D.

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

Mark

Deo, R. ; Nalls, M. A. ; Avery, C. L. ; Smith, Gustav ^LU ; Evans, D. S. ; Keller, M. F. ; Butler, A. M. ; Buxbaum, S. G. ; Li, G. and Quibrera, P. Miguel , et al. (2013) In Heart Rhythm 10(3). p.401-408

Abstract: 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... (More); 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. (Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/3657236

author

Deo, R. ; Nalls, M. A. ; Avery, C. L. ; Smith, Gustav ^LU ; Evans, D. S. ; Keller, M. F. ; Butler, A. M. ; Buxbaum, S. G. ; Li, G. and Quibrera, P. Miguel , et al. (More)

Deo, R. ; Nalls, M. A. ; Avery, C. L. ; Smith, Gustav ^LU ; Evans, D. S. ; Keller, M. F. ; Butler, A. M. ; Buxbaum, S. G. ; Li, G. ; Quibrera, P. Miguel ; Smith, E. N. ; Tanaka, T. ; Akylbekova, E. L. ; Alonso, A. ; Arking, D. E. ; Benjamin, E. J. ; Berenson, G. S. ; Bis, J. C. ; Chen, L. Y. ; Chen, W. ; Cummings, S. R. ; Ellinor, P. T. ; Evans, M. K. ; Ferrucci, L. ; Fox, E. R. ; Heckbert, S. R. ; Heiss, G. ; Hsueh, W. C. ; Kerr, K. F. ; Limacher, M. C. ; Liu, Y. ; Lubitz, S. A. ; Magnani, J. W. ; Mehra, R. ; Marcus, G. M. ; Murray, S. S. ; Newman, A. B. ; Njajou, O. ; North, K. E. ; Paltoo, D. N. ; Psaty, B. M. ; Redline, S. S. ; Reiner, A. P. ; Robinson, J. G. ; Rotter, J. I. ; Samdarshi, T. E. ; Schnabel, R. B. ; Schork, N. J. ; Singleton, A. B. ; Siscovick, D. ; Soliman, E. Z. ; Sotoodehnia, N. ; Srinivasan, S. R. ; Taylor, H. A. ; Trevisan, M. ; Zhang, Z. ; Zonderman, A. B. ; Newton-Cheh, C. and Whitsel, E. A. (Less)

organization

publishing date

2013

type

Contribution to journal

publication status

published

subject

Cardiac and Cardiovascular Systems

keywords

African Americans, Heart rate, Singe nucleotide polymorphisms, Meta-analysis

in

Heart Rhythm

volume

10

issue

3

pages

401 - 408

publisher

Elsevier

external identifiers

wos:000315773000017
scopus:84875318876
pmid:23183192

ISSN

1547-5271

DOI

10.1016/j.hrthm.2012.11.014

language

English

LU publication?

yes

id

560f91ec-2672-45a1-9d41-628fa8549415 (old id 3657236)

date added to LUP

2016-04-01 09:48:36

date last changed

2022-01-25 08:58:50

@article{560f91ec-2672-45a1-9d41-628fa8549415,
  abstract     = {{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 &lt;= 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.}},
  author       = {{Deo, R. and Nalls, M. A. and Avery, C. L. and Smith, Gustav and Evans, D. S. and Keller, M. F. and Butler, A. M. and Buxbaum, S. G. and Li, G. and Quibrera, P. Miguel and Smith, E. N. and Tanaka, T. and Akylbekova, E. L. and Alonso, A. and Arking, D. E. and Benjamin, E. J. and Berenson, G. S. and Bis, J. C. and Chen, L. Y. and Chen, W. and Cummings, S. R. and Ellinor, P. T. and Evans, M. K. and Ferrucci, L. and Fox, E. R. and Heckbert, S. R. and Heiss, G. and Hsueh, W. C. and Kerr, K. F. and Limacher, M. C. and Liu, Y. and Lubitz, S. A. and Magnani, J. W. and Mehra, R. and Marcus, G. M. and Murray, S. S. and Newman, A. B. and Njajou, O. and North, K. E. and Paltoo, D. N. and Psaty, B. M. and Redline, S. S. and Reiner, A. P. and Robinson, J. G. and Rotter, J. I. and Samdarshi, T. E. and Schnabel, R. B. and Schork, N. J. and Singleton, A. B. and Siscovick, D. and Soliman, E. Z. and Sotoodehnia, N. and Srinivasan, S. R. and Taylor, H. A. and Trevisan, M. and Zhang, Z. and Zonderman, A. B. and Newton-Cheh, C. and Whitsel, E. A.}},
  issn         = {{1547-5271}},
  keywords     = {{African Americans; Heart rate; Singe nucleotide polymorphisms; Meta-analysis}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{401--408}},
  publisher    = {{Elsevier}},
  series       = {{Heart Rhythm}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1016/j.hrthm.2012.11.014}},
  doi          = {{10.1016/j.hrthm.2012.11.014}},
  volume       = {{10}},
  year         = {{2013}},
}

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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