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

5 years ago

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

Smith AV, Chasman DI, Alonso A, Paré G, Müller-Nurasyid M, Christophersen IE, Macfarlane P, Lehtimäki T, Benjamin EJ, Arking DE, Sotoodehnia N, Van Wagoner DR, van der Harst P, Lunetta KL, Felix SB, Teumer A, Verweij N, Weng LC, Gudnason V, Heckbert SR, Taylor KD, Kleber ME, Weeke PE, Albert CM, Guo X, Sinner MF, Heeringa J, Dörr M, Delgado GE, Jukema JW, Roden DM, Uitterlinden AG, Engström G, Kähönen M, Rotter JI, Waldenberger M, Franco OH, Yao J, Melander O, Lubitz SA, Denny JC, Harris TB, Smith JG, Kääb S, Ellinor PT, Smith JD, Lin HJ, Psaty BM, Stricker BH, März W, Soliman EZ, Barnard J, Thériault S, Geelhoed B, Launer LJ, Conen D, Ford I, Nikus K, Trompet S, Rienstra M, Krijthe BP, Chung MK, Klarin D, Rose LM, Teixeira PL, Lyytikäinen LP, Bis JC, Völker U, Shoemaker MB, Martinsson A

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.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28900195

DOI: PubMed:28900195