Year: 2016
Type: article
Study design: Observational Study
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 × 10–8). 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.
Source: Scientific Reports
DOI: 10.1038/srep35371
Authors: Honghuang Lin, Martina Mueller-Nurasyid, Albert V. Smith, Dan E. Arking, John Barnard, Traci M. Bartz, Kathryn L. Lunetta, Kurt Lohman, Marcus E. Kleber, Steven A. Lubitz, Bastiaan Geelhoed, Stella Trompet, Maartje N. Niemeijer, Tim Kacprowski, Daniel I. Chasman, Derek Klarin, Moritz F. Sinner, Melanie Waldenberger, Thomas Meitinger, Tamara B. Harris, Lenore J. Launer, Elsayed Z. Soliman, Lin Y. Chen, Jonathan D. Smith, David R. Van Wagoner, Jerome I. Rotter, Bruce M. Psaty, Zhijun Xie, Audrey E. Hendricks, Jingzhong Ding, Graciela E. Delgado, Niek Verweij, Pim van der Harst, Peter W. Macfarlane, Ian Ford, Albert Hofman, André Uitterlinden, Jan Heeringa, Oscar H. Franco, Jan A. Kors, Stefan Weiss, Henry Völzke, Lynda M. Rose, Pradeep Natarajan, Sekar Kathiresan, Stefan Kääb, Vilmundur Gudnason, Alvaro Alonso, Mina K. Chung, Susan R. Heckbert, Emelia J. Benjamin, Yongmei Liu, Winfried März, Michiel Rienstra, J. Wouter Jukema, Bruno H. Stricker, Marcus Dörr, Christine M. Albert, Patrick T. Ellinor
Institutions: Boston University, Framingham Heart Study, Helmholtz Munich, German Centre for Cardiovascular Research, Ludwig-Maximilians-Universität München, University of Iceland, Icelandic Heart Association, Johns Hopkins University, Cleveland Clinic, University of Washington, Wake Forest University Health Sciences, Wake Forest University, Heidelberg University, Medizinische Fakultät Mannheim, Harvard University, Massachusetts General Hospital, University Medical Center Groningen, University of Groningen, Leiden University Medical Center, Erasmus MC, Universität Greifswald, Brigham and Women's Hospital, Broad Institute, Institut für Humangenetik, Technical University of Munich, National Institutes of Health, National Institute on Aging, University of Minnesota, The Lundquist Institute, Harbor–UCLA Medical Center, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute, University of Colorado Denver, University of Glasgow, Universitätsmedizin Greifswald, Emory University, Medical University of Graz, Synlab (Germany), Dutch Health Care Inspectorate
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: American Heart Association, Bristol-Myers Squibb, Cleveland Clinic, Johns Hopkins University, Georgia Clinical and Translational Science Alliance, Kompetenznetz Vorhofflimmern, European Commission, Fondation Leducq, ZonMw, Erasmus Universiteit Rotterdam, Bundesministerium für Bildung und Forschung, Nierstichting, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Siemens, Deutsche Herzstiftung, Universität Greifswald, Ministry of Cultural Affairs, National Institutes of Health, Helmholtz Zentrum München, Netherlands Heart Institute, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, U.S. National Library of Medicine, National Center for Research Resources
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OpenAlex ID: W2551800188