Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium

Lu Chen Weng, Kathryn L. Lunetta, Martina Müller-Nurasyid, Albert Vernon Smith, Sébastien Thériault, Peter E. Weeke, John Barnard, Joshua C. Bis, Leo Pekka Lyytikäinen, Marcus E. Kleber, Andreas Martinsson, Henry J. Lin, Michiel Rienstra, Stella Trompet, Bouwe P. Krijthe, Marcus Dörr, Derek Klarin, Daniel I. Chasman, Moritz F. Sinner, Melanie WaldenbergerLenore J. Launer, Tamara B. Harris, Elsayed Z. Soliman, Alvaro Alonso, Guillaume Paré, Pedro L. Teixeira, Joshua C. Denny, M. Benjamin Shoemaker, David R. Van Wagoner, Jonathan D. Smith, Bruce M. Psaty, Nona Sotoodehnia, Kent D. Taylor, Mika Kähönen, Kjell Nikus, Graciela E. Delgado, Olle Melander, Gunnar Engström, Jie Yao, Xiuqing Guo, Ingrid E. Christophersen, Patrick T. Ellinor, Bastiaan Geelhoed, Niek Verweij, Peter Macfarlane, Ian Ford, Jan Heeringa, Oscar H. Franco, André G. Uitterlinden, Uwe Völker, Alexander Teumer, Lynda M. Rose, Stefan Kääb, Vilmundur Gudnason, Dan E. Arking, David Conen, Dan M. Roden, Mina K. Chung, Susan R. Heckbert, Emelia J. Benjamin, Terho Lehtimäki, Winfried März, J. Gustav Smith, Jerome I. Rotter, Pim Van Der Harst, J. Wouter Jukema, Bruno H. Stricker, Stephan B. Felix, Christine M. Albert, Steven A. Lubitz

Research output: Contribution to journalArticlepeer-review


It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

Original languageEnglish (US)
Article number11303
JournalScientific reports
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General


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