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Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.

Ingrid Elisabeth ChristophersenMichiel RienstraCarolina RoselliXiaoyan YinBastiaan GeelhoedJohn BarnardHonghuang LinDan E ArkingAlbert Vernon SmithChristine M AlbertMark ChaffinNathan R TuckerMolong LiDerek KlarinNathan A BihlmeyerSiew-Kee LowPeter E WeekeMartina Müller-NurasyidJ Gustav SmithJennifer A BrodyMaartje N NiemeijerMarcus DörrStella TrompetJennifer E HuffmanStefan GustafssonClaudia SchurmannMarcus Edi KleberLeo-Pekka LyytikainenIlkka SeppäläRainer MalikAndrea R V R HorimotoMarco PerezJuha SinisaloStefanie AeschbacherSébastien ThériaultJie YaoFarid RadmaneshStefan WeissAlexander TeumerSeung Hoan ChoiLu-Chen WengSebastian ClaussRajat DeoDaniel J RaderSvati H ShahAlbert SunJemma C HopewellStephanie DebetteGanesh ChauhanQiong YangBradford B WorrallGuillaume ParéYoichiro KamataniYanick Paco HagemeijerNiek VerweijJoylene E SilandMichiaki KuboJonathan D SmithDavid R Van WagonerJoshua C BisSiegfried PerzBruce M PsatyPaul M RidkerJared W MagnaniTamara B HarrisLenore J LaunerM Benjamin ShoemakerSandosh PadmanabhanJeffrey HaesslerTraci M BartzMelanie WaldenbergerPeter LichtnerMarina ArendtJose Eduardo KriegerMika KähönenLorenz RischAlfredo J MansurAnnette PetersBlair Hamilton SmithLars LindStuart A ScottYingchang LuErwin B BottingerJussi HernesniemiCecilia M LindgrenJorge A WongJie HuangMarkku EskolaAndrew P MorrisIan FordAlex P ReinerGraciela DelgadoLin Y ChenYii-Der Ida ChenRoopinder K SandhuMan LiEric BoerwinkleLewin EiseleLars LannfeltNatalia RostChristopher D AndersonKent D TaylorArchie I CampbellPatrik K MagnussonDavid PorteousLynne J HockingEfthymia VlachopoulouNancy L PedersenKjell NikusMarju Orho-MelanderAnders HamstenJan HeeringaJoshua C DennyJennifer KriebelDawood DarbarChristopher Newton-ChehChristian ShafferPeter W MacfarlaneStefanie Heilmann-HeimbachPeter AlmgrenPaul L HuangNona SotoodehniaElsayed Z SolimanAndre G UitterlindenAlbert HofmanOscar H FrancoUwe VölkerKarl-Heinz JöckelMoritz F SinnerHenry J LinXiuqing Guonull nullnull nullMartin DichgansErik IngelssonCharles KooperbergOlle MelanderRuth J F LoosJari LaurikkaDavid ConenJonathan RosandPim van der HarstMarja-Liisa LokkiSekar KathiresanAlexandre PereiraJohan Wouter JukemaCaroline HaywardJerome I RotterWinfried MärzTerho LehtimäkiBruno H StrickerMina K ChungStephan B FelixVilmundur GudnasonAlvaro AlonsoDan M RodenStefan KääbDaniel I ChasmanSusan R HeckbertEmelia J BenjaminToshihiro TanakaKathryn L LunettaSteven A LubitzPatrick T Ellinornull null
Published in: Nature genetics (2017)
Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.
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