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Gene-gene Interaction Analyses for Atrial Fibrillation.

Publication ,  Journal Article
Lin, H; Mueller-Nurasyid, M; Smith, AV; Arking, DE; Barnard, J; Bartz, TM; Lunetta, KL; Lohman, K; Kleber, ME; Lubitz, SA; Geelhoed, B; Xie, Z ...
Published in: Sci Rep
November 8, 2016

Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27-1.65, P = 4.3 × 10-8). Eight additional gene-gene interactions were also marginally significant (P < 5 × 10-7). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 8, 2016

Volume

6

Start / End Page

35371

Location

England

Related Subject Headings

  • Potassium Channels
  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Muscle Proteins
  • Multivariate Analysis
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Humans
 

Citation

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Lin, H., Mueller-Nurasyid, M., Smith, A. V., Arking, D. E., Barnard, J., Bartz, T. M., … Ellinor, P. T. (2016). Gene-gene Interaction Analyses for Atrial Fibrillation. Sci Rep, 6, 35371. https://doi.org/10.1038/srep35371
Lin, Honghuang, Martina Mueller-Nurasyid, Albert V. Smith, Dan E. Arking, John Barnard, Traci M. Bartz, Kathryn L. Lunetta, et al. “Gene-gene Interaction Analyses for Atrial Fibrillation.Sci Rep 6 (November 8, 2016): 35371. https://doi.org/10.1038/srep35371.
Lin H, Mueller-Nurasyid M, Smith AV, Arking DE, Barnard J, Bartz TM, et al. Gene-gene Interaction Analyses for Atrial Fibrillation. Sci Rep. 2016 Nov 8;6:35371.
Lin, Honghuang, et al. “Gene-gene Interaction Analyses for Atrial Fibrillation.Sci Rep, vol. 6, Nov. 2016, p. 35371. Pubmed, doi:10.1038/srep35371.
Lin H, Mueller-Nurasyid M, Smith AV, Arking DE, Barnard J, Bartz TM, Lunetta KL, Lohman K, Kleber ME, Lubitz SA, Geelhoed B, Trompet S, Niemeijer MN, Kacprowski T, Chasman DI, Klarin D, Sinner MF, Waldenberger M, Meitinger T, Harris TB, Launer LJ, Soliman EZ, Chen LY, Smith JD, Van Wagoner DR, Rotter JI, Psaty BM, Xie Z, Hendricks AE, Ding J, Delgado GE, Verweij N, van der Harst P, Macfarlane PW, Ford I, Hofman A, Uitterlinden A, Heeringa J, Franco OH, Kors JA, Weiss S, Völzke H, Rose LM, Natarajan P, Kathiresan S, Kääb S, Gudnason V, Alonso A, Chung MK, Heckbert SR, Benjamin EJ, Liu Y, März W, Rienstra M, Jukema JW, Stricker BH, Dörr M, Albert CM, Ellinor PT. Gene-gene Interaction Analyses for Atrial Fibrillation. Sci Rep. 2016 Nov 8;6:35371.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 8, 2016

Volume

6

Start / End Page

35371

Location

England

Related Subject Headings

  • Potassium Channels
  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Muscle Proteins
  • Multivariate Analysis
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Humans