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Lin, H.* ; Müller-Nurasyid, M. ; Smith, A.V.* ; Arking, D.E.* ; Barnard, J.* ; Bartz, T.M.* ; Lunetta, K.L.* ; Lohman, K.* ; Kleber, M.E.* ; Lubitz, S.A.* ; Geelhoed, B.* ; Trompet, S.* ; Niemeijer, M.N.* ; Kacprowski, T.* ; Chasman, D.I.* ; Klarin, D.* ; Sinner, M.F.* ; Waldenberger, M. ; Meitinger, T. ; Harris, T.B.* ; Launer, L.J.* ; Soliman, E.Z.* ; Chen, L.Y.* ; Smith, J.D.* ; van Wagoner, D.R.* ; Rotter, J.I.* ; Psaty, B.M.* ; Xie, Z.* ; Hendricks, A.E.* ; Ding, J.* ; Delgado, G.E.* ; Verweij, N.* ; van der Harst, P.* ; Macfarlane, P.W.* ; Ford, I.* ; Hofman, A.* ; Uitterlinden, A.* ; Heeringa, J.* ; Franco, O.H.* ; Kors, J.A.* ; Weiss, S.* ; Völzke, H.* ; Rose, L.M.* ; Natarajan, P.* ; Kathiresan, S.* ; Kääb, S.* ; Gudnason, V.* ; Alonso, A.* ; Chung, M.K.* ; Heckbert, S.R.* ; Benjamin, E.J.* ; Liu, Y.* ; Marz, W.* ; Rienstra, M.* ; Jukema, J.W.* ; Stricker, B.H.* ; Dörr, M.* ; Albert, C.M.* ; Ellinor, P.T.*

Gene-gene interaction analyses for atrial fibrillation.

Sci. Rep. 6:35371 (2016)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Protein-interaction Maps; Familial Aggregation; Missing Heritability; Breast-cancer; Association; Risk; Variants; Disease; Susceptibility; Metaanalysis
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Journal Scientific Reports
Quellenangaben Volume: 6, Issue: , Pages: , Article Number: 35371 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-504091-001
G-500700-001
PubMed ID 27824142
DOI 10.1038/srep35371
WOS ID WOS:000387283300001
Scopus ID 84994400001
Erfassungsdatum 2016-11-21
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