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Gene-gene Interaction Analyses for Atrial Fibrillation.

TitleGene-gene Interaction Analyses for Atrial Fibrillation.
Publication TypeJournal Article
Year of Publication2016
AuthorsLin 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 LYee, 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, J Jukema W, Stricker BH, Dörr M, Albert CM
Secondary AuthorsEllinor PT
JournalSci Rep
Volume6
Pagination35371
Date Published2016 11 08
ISSN2045-2322
KeywordsAged, Atrial Fibrillation, Cohort Studies, Epistasis, Genetic, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Male, Membrane Transport Proteins, Middle Aged, Multivariate Analysis, Muscle Proteins, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Potassium Channels
Abstract

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). Eight additional gene-gene interactions were also marginally significant (P 

DOI10.1038/srep35371
Alternate JournalSci Rep
PubMed ID27824142
PubMed Central IDPMC5099695
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
T32 HL007208 / HL / NHLBI NIH HHS / United States
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