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

Weng, Lu Chen; Lunetta, Kathryn L; Müller-Nurasyid, Martina; Smith, Albert Vernon; Thériault, Sébastien; Weeke, Peter E.; Barnard, John; Bis, Joshua C.; Lyytikäinen, Leo-Pekka and Kleber, Marcus E, et al. (2017) In Scientific Reports 7(1).
Abstract

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... (More)

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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Scientific Reports
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Nature Publishing Group
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  • scopus:85029282039
  • wos:000410297900017
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2045-2322
DOI
10.1038/s41598-017-09396-7
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English
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@article{1b7c11b0-87ad-48bd-8757-b2e5471becbe,
  abstract     = {<p>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 &gt; 65 years (interaction p-value = 4.0 × 10<sup>-5</sup>). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10<sup>-8</sup>). 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.</p>},
  articleno    = {11303},
  author       = {Weng, Lu Chen and Lunetta, Kathryn L and Müller-Nurasyid, Martina and Smith, Albert Vernon and Thériault, Sébastien and Weeke, Peter E. and Barnard, John and Bis, Joshua C. and Lyytikäinen, Leo-Pekka and Kleber, Marcus E and Martinsson, Andreas and Lin, Henry J. and Rienstra, Michiel and Trompet, Stella and Krijthe, Bouwe P and Dörr, Marcus and Klarin, Derek and Chasman, Daniel I. and Sinner, Moritz F and Waldenberger, Melanie and Launer, Lenore J. and Harris, Tamara B and Soliman, Elsayed Z and Alonso, Alvaro and Paré, Guillaume and Teixeira, Pedro L. and Denny, Joshua C and Shoemaker, M. Benjamin and Van Wagoner, David R and Smith, Jonathan D and Psaty, Bruce M. and Sotoodehnia, Nona and Taylor, Kent D and Kähönen, Mika and Nikus, Kjell and Delgado, Graciela E. and Melander, Olle and Engström, Gunnar and Yao, Jie and Guo, Xiuqing and Christophersen, Ingrid E. and Ellinor, Patrick T and Geelhoed, Bastiaan and Verweij, Niek and Macfarlane, Peter and Ford, Ian and Heeringa, Jan and Franco, Oscar H and Uitterlinden, André G and Völker, Uwe and Teumer, Alexander and Rose, Lynda M. and Kääb, Stefan and Gudnason, Vilmundur and Arking, Dan E. and Conen, David and Roden, Dan M and Chung, Mina K and Heckbert, Susan R and Benjamin, Emelia J and Lehtimäki, Terho and März, Winfried and Smith, Gustav and Rotter, Jerome I. and van der Harst, Pim and Jukema, J. Wouter and Stricker, Bruno H and Felix, Stephan B and Albert, Christine M and Lubitz, Steven A},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation : The AFGen Consortium},
  url          = {http://dx.doi.org/10.1038/s41598-017-09396-7},
  volume       = {7},
  year         = {2017},
}