Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

Replication of the Association of the 6q22.31c Locus near GJA1 with Pulse Rate in the Korean Population

  • Kim, Nam-Hee (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Kim, Young-Jin (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Oh, Ji-Hee (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Cho, Yoon-Shin (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health)
  • Received : 2012.05.03
  • Accepted : 2012.05.22
  • Published : 2012.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Pulse rate is known to be related to diverse phenotypes, such as cardiovascular diseases, lifespan, arrhythmia, hypertension, lipids, diabetes, and menopause. We have reported two genomewide significant genetic loci responsible for the variation in pulse rate as a part of the Korea Association Resource (KARE) project, the genomewide association study (GWAS) that was conducted with 352,228 single nucleoride polymorphisms typed in 8,842 subjects in the Korean population. GJA1 was implied as a functionally causal gene for pulse rate from the KARE study, but lacked evidence of replication. To re-evaluate the association of a locus near GJA1 with pulse rate, we looked up this signal in another GWAS conducted in a Health Examinee-shared cohort of 3,703 samples. Not only we were able to confirm two pulse rate loci (1q32.2a near CD46 and 6q22.13c near LOCL644502) identified in the KARE GWAS, we also replicated a locus (6q22.31c) near GJA1 by the lookup in the Health Examinee GWAS. Considering that the GJA1-encoded protein is a major component of cardiac gap junctions, a functional study might be necessary to validate its genuine molecular biological role in the synchronized contraction of the heart.

Keywords

References

  1. Perret-Guillaume C, Joly L, Benetos A. Heart rate as a risk factor for cardiovascular disease. Prog Cardiovasc Dis 2009;52:6-10. https://doi.org/10.1016/j.pcad.2009.05.003
  2. Zhang GQ, Zhang W. Heart rate, lifespan, and mortality risk. Ageing Res Rev 2009;8:52-60. https://doi.org/10.1016/j.arr.2008.10.001
  3. Mounier-Vehier C, Lequeuche B, Carre A. Heart rate and lipids. Ann Cardiol Angeiol (Paris) 1998;47:425-428.
  4. Spies C, Otte C, Kanaya A, Pipkin SS, Schiller NB, Whooley MA. Association of metabolic syndrome with exercise capacity and heart rate recovery in patients with coronary heart disease in the heart and soul study. Am J Cardiol 2005;95:1175-1179. https://doi.org/10.1016/j.amjcard.2005.01.045
  5. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009;41:527-534. https://doi.org/10.1038/ng.357
  6. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559-575. https://doi.org/10.1086/519795
  7. Ioannidis JP, Patsopoulos NA, Evangelou E. Heterogeneity in meta-analyses of genome-wide association investigations. PLoS One 2007;2:e841. https://doi.org/10.1371/journal.pone.0000841
  8. Wang G, Liszewski MK, Chan AC, Atkinson JP. Membrane cofactor protein (MCP; CD46): isoform-specific tyrosine phosphorylation. J Immunol 2000;164:1839-1846. https://doi.org/10.4049/jimmunol.164.4.1839
  9. Dooley DC, Oppenlander BK, Xiao M. Analysis of primitive CD34- and CD34+ hematopoietic cells from adults: gain and loss of CD34 antigen by undifferentiated cells are closely linked to proliferative status in culture. Stem Cells 2004;22:556-569. https://doi.org/10.1634/stemcells.22-4-556
  10. Wang B, Wen Q, Xie X, Liu S, Liu M, Tao Y, et al. Mutation analysis of Connexon43 gene in Chinese patients with congenital heart defects. Int J Cardiol 2010;145:487-489. https://doi.org/10.1016/j.ijcard.2009.06.026
  11. Britz-Cunningham SH, Shah MM, Zuppan CW, Fletcher WH. Mutations of the Connexin43 gap-junction gene in patients with heart malformations and defects of laterality. N Engl J Med 1995;332:1323-1329. https://doi.org/10.1056/NEJM199505183322002
  12. Eijgelsheim M, Newton-Cheh C, Sotoodehnia N, de Bakker PI, Müller M, Morrison AC, et al. Genome-wide association analysis identifies multiple loci related to resting heart rate. Hum Mol Genet 2010;19:3885-3894. https://doi.org/10.1093/hmg/ddq303