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

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Weng, Lu ChenBroad Institute,Massachusetts General Hospital (author)

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

Article/chapterEnglish2017

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2017-09-12
Springer Science and Business Media LLC,2017

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LIBRIS-ID:oai:lup.lub.lu.se:1b7c11b0-87ad-48bd-8757-b2e5471becbe
https://lup.lub.lu.se/record/1b7c11b0-87ad-48bd-8757-b2e5471becbeURI
https://doi.org/10.1038/s41598-017-09396-7DOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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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Lunetta, Kathryn LBoston University (author)
Müller-Nurasyid, MartinaUniversity Hospital Munich,Helmholtz Zentrum München,Ludwig-Maximilian University of Munich,German Centre for Cardiovascular Research (author)
Smith, Albert VernonUniversity of Iceland,Icelandic Heart Association (author)
Thériault, SébastienMcMaster University (author)
Weeke, Peter E.Vanderbilt University,Copenhagen University Hospital (author)
Barnard, JohnCleveland Clinic Foundation (author)
Bis, Joshua C.University of Washington (author)
Lyytikäinen, Leo-PekkaUniversity of Tampere (author)
Kleber, Marcus EHeidelberg University (author)
Martinsson, AndreasLund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-asm (author)
Lin, Henry J.University of California, Los Angeles (author)
Rienstra, MichielUniversity of Groningen (author)
Trompet, StellaLeiden University Medical Centre (author)
Krijthe, Bouwe PErasmus University Medical Center (author)
Dörr, MarcusUniversity Medicine Greifswald,German Centre for Cardiovascular Research (author)
Klarin, DerekHarvard University,Massachusetts General Hospital,Broad Institute (author)
Chasman, Daniel I.Brigham and Women's Hospital / Harvard Medical School (author)
Sinner, Moritz FLudwig-Maximilian University of Munich,German Centre for Cardiovascular Research (author)
Waldenberger, MelanieHelmholtz Zentrum München,German Centre for Cardiovascular Research (author)
Launer, Lenore J.National Institute on Aging, United States (author)
Harris, Tamara BNational Institute on Aging, United States (author)
Soliman, Elsayed ZWake Forest University (author)
Alonso, AlvaroEmory University (author)
Paré, GuillaumeMcMaster University (author)
Teixeira, Pedro L.Vanderbilt University (author)
Denny, Joshua CVanderbilt University (author)
Shoemaker, M. BenjaminVanderbilt University (author)
Van Wagoner, David RCleveland Clinic Foundation (author)
Smith, Jonathan DCleveland Clinic Foundation (author)
Psaty, Bruce M.University of Washington,Kaiser Permanente Research Institute (author)
Sotoodehnia, NonaKaiser Permanente Research Institute,University of Washington (author)
Taylor, Kent DUniversity of California, Los Angeles (author)
Kähönen, MikaTampere University Hospital,University of Tampere (author)
Nikus, KjellUniversity of Tampere,Tampere University Hospital (author)
Delgado, Graciela E.Heidelberg University (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ome (author)
Engström, GunnarLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)smi-gen (author)
Yao, JieUniversity of California, Los Angeles (author)
Guo, XiuqingUniversity of California, Los Angeles (author)
Christophersen, Ingrid E.Baerum Hospital,Massachusetts General Hospital,Broad Institute (author)
Ellinor, Patrick TMassachusetts General Hospital,Broad Institute (author)
Geelhoed, BastiaanUniversity of Groningen (author)
Verweij, NiekUniversity of Groningen (author)
Macfarlane, PeterUniversity of Glasgow (author)
Ford, IanUniversity of Glasgow (author)
Heeringa, JanErasmus University Medical Center (author)
Franco, Oscar HErasmus University Medical Center (author)
Uitterlinden, André GErasmus University Medical Center (author)
Völker, UweGerman Centre for Cardiovascular Research,University Medicine Greifswald (author)
Teumer, AlexanderUniversity Medicine Greifswald,German Centre for Cardiovascular Research (author)
Rose, Lynda M.Brigham and Women's Hospital / Harvard Medical School (author)
Kääb, StefanLudwig-Maximilian University of Munich,German Centre for Cardiovascular Research (author)
Gudnason, VilmundurUniversity of Iceland,Icelandic Heart Association (author)
Arking, Dan E.Johns Hopkins University (author)
Conen, DavidUniversity Hospital Basel (author)
Roden, Dan MVanderbilt University (author)
Chung, Mina KCleveland Clinic Foundation (author)
Heckbert, Susan RKaiser Permanente Research Institute,University of Washington (author)
Benjamin, Emelia JBoston University (author)
Lehtimäki, TerhoUniversity of Tampere (author)
März, WinfriedMedical University of Graz,Heidelberg University (author)
Smith, GustavLund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-gvs (author)
Rotter, Jerome I.University of California, Los Angeles (author)
van der Harst, PimUniversity of Groningen (author)
Jukema, J. WouterInteruniversity Cardiology Institute of the Netherlands,Leiden University Medical Centre (author)
Stricker, Bruno HDutch Health Care Inspectorate,Erasmus University Medical Center (author)
Felix, Stephan BGerman Centre for Cardiovascular Research,University Medicine Greifswald (author)
Albert, Christine MBrigham and Women's Hospital / Harvard Medical School (author)
Lubitz, Steven AMassachusetts General Hospital,Broad Institute (author)
Broad InstituteMassachusetts General Hospital (creator_code:org_t)

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By the author/editor: Weng, Lu Chen; Lunetta, Kathryn ...; Müller-Nurasyid, ...; Smith, Albert Ve ...; Thériault, Sébas ...; Weeke, Peter E.; show more...; Barnard, John; Bis, Joshua C.; Lyytikäinen, Leo ...; Kleber, Marcus E; Martinsson, Andr ...; Lin, Henry J.; Rienstra, Michie ...; Trompet, Stella; Krijthe, Bouwe P; Dörr, Marcus; Klarin, Derek; Chasman, Daniel ...; Sinner, Moritz F; Waldenberger, Me ...; Launer, Lenore J ...; Harris, Tamara B; Soliman, Elsayed ...; Alonso, Alvaro; Paré, Guillaume; Teixeira, Pedro ...; Denny, Joshua C; Shoemaker, M. Be ...; Van Wagoner, Dav ...; Smith, Jonathan ...; Psaty, Bruce M.; Sotoodehnia, Non ...; Taylor, Kent D; Kähönen, Mika; Nikus, Kjell; Delgado, Graciel ...; Melander, Olle; Engström, Gunnar; Yao, Jie; Guo, Xiuqing; Christophersen, ...; Ellinor, Patrick ...; Geelhoed, Bastia ...; Verweij, Niek; Macfarlane, Pete ...; Ford, Ian; Heeringa, Jan; Franco, Oscar H; Uitterlinden, An ...; Völker, Uwe; Teumer, Alexande ...; Rose, Lynda M.; Kääb, Stefan; Gudnason, Vilmun ...; Arking, Dan E.; Conen, David; Roden, Dan M; Chung, Mina K; Heckbert, Susan ...; Benjamin, Emelia ...; Lehtimäki, Terho; März, Winfried; Smith, Gustav; Rotter, Jerome I ...; van der Harst, P ...; Jukema, J. Woute ...; Stricker, Bruno ...; Felix, Stephan B; Albert, Christin ...; Lubitz, Steven A; show less...

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