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

Lu-Chen WengKathryn L LunettaMartina Müller-NurasyidAlbert Vernon SmithSébastien ThériaultPeter E WeekeJohn BarnardJoshua C BisLeo-Pekka LyytikainenMarcus Edi KleberAndreas MartinssonHenry J LinMichiel RienstraStella TrompetBouwe P KrijtheMarcus DörrDerek KlarinDaniel I ChasmanMoritz F SinnerMelanie WaldenbergerLenore J LaunerTamara B HarrisElsayed Z SolimanAlvaro AlonsoGuillaume ParéPedro L TeixeiraJoshua C DennyM Benjamin ShoemakerDavid R Van WagonerJonathan D SmithBruce M PsatyNona SotoodehniaKent D TaylorMika KähönenKjell NikusGraciela E DelgadoOlle MelanderGunnar EngströmJie YaoXiuqing GuoIngrid E ChristophersenPatrick T EllinorBastiaan GeelhoedNiek VerweijPeter MacfarlaneIan FordJan HeeringaOscar H FrancoAndré G UitterlindenUwe VölkerAlexander TeumerLynda M RoseStefan KääbVilmundur GudnasonDan E ArkingDavid ConenDan M RodenMina K ChungSusan R HeckbertEmelia J BenjaminTerho LehtimäkiWinfried MärzJ Gustav SmithJerome I RotterPim van der HarstJ Wouter JukemaBruno H StrickerStephan B FelixChristine M AlbertSteven A Lubitz
Published in: Scientific reports (2017)
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.
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