Multi-ethnic genome-wide association study for atrial fibrillation.
Carolina RoselliMark D ChaffinLu-Chen WengStefanie AeschbacherGustav AhlbergChristine M AlbertPeter AlmgrenAlvaro AlonsoChristopher D AndersonKrishna G AragamDan E ArkingJohn BarnardTraci M BartzEmelia J BenjaminNathan A BihlmeyerJoshua C BisHeather L BloomEric BoerwinkleErwin B BottingerJennifer A BrodyHugh CalkinsArchie I CampbellThomas P CappolaJohn CarlquistDaniel I ChasmanLin Y ChenYii-Der Ida ChenEue-Keun ChoiSeung Hoan ChoiIngrid Elisabeth ChristophersenMina K ChungJohn W ColeDavid ConenJames CookHarry J CrijnsMichael J CutlerScott M DamrauerBrian R DanielsDawood DarbarGraciela DelgadoJoshua C DennyMartin DichgansMarcus DörrElton A M P DudinkSamuel C DudleyNada EsaTõnu EskoMarkku EskolaDiane FatkinStephan B FelixIan FordOscar H FrancoBastiaan GeelhoedRaji P GrewalVilmundur GudnasonXiuqing GuoNamrata GuptaStefan GustafssonRebecca GutmannAnders HamstenTamara B HarrisCaroline HaywardSusan R HeckbertJussi HernesniemiLynne J HockingAlbert HofmanAndrea R V R HorimotoJie HuangPaul L HuangJennifer E HuffmanErik IngelssonEsra Gucuk IpekKaoru ItoJordi Jimenez-CondeRenee JohnsonJohan Wouter JukemaStefan KääbMika KähönenYoichiro KamataniJohn P KaneAdnan KastratiSekar KathiresanPetra Katschnig-WinterMaryam KavousiThorsten KesslerBas L KietselaerPaulus KirchhofMarcus Edi KleberStacey KnightJose Eduardo KriegerMichiaki KuboLenore J LaunerJari LaurikkaTerho LehtimäkiKirsten LeineweberRozenn N LemaitreMan LiHong Euy LimHenry J LinHonghuang LinLars LindCecilia M LindgrenMarja-Liisa LokkiBarry LondonRuth J F LoosSiew-Kee LowYingchang LuLeo-Pekka LyytikainenPeter W MacfarlanePatrik K E MagnussonAnubha MahajanRainer MalikAlfredo J MansurGregory M MarcusLauren MargolinKenneth B MarguliesWinfried MärzDavid D McManusOlle MelanderSanghamitra MohantyJay A MontgomeryMichael P MorleyAndrew P MorrisMartina Müller-NuraysidAndrea NataleSaman NazarianBenjamin NeumannChristopher Newton-ChehMaartje N NiemeijerKjell NikusPeter NilssonRaymond NoordamHeidi OellersMorten S OlesenMarju Orho-MelanderSandosh PadmanabhanHui-Nam PakGuillaume ParéNancy L PedersenJoanna PeraAlexandre PereiraDavid PorteousBruce M PsatySara L PulitClive R PullingerDaniel J RaderLena RefsgaardMarta RibasesPaul M RidkerMichiel RienstraLorenz RischDan M RodenJonathan RosandMichael A RosenbergNatalia RostJerome I RotterSamir SabaRoopinder K SandhuRenate B SchnabelKatharina SchrammHeribert SchunkertClaudia SchurmanStuart A ScottIlkka SeppäläChristian ShafferSvati ShahAlaa A ShalabyJaemin ShimM Benjamin ShoemakerJoylene E SilandJuha SinisaloMoritz F SinnerAgnieszka SlowikAlbert Vernon SmithBlair Hamilton SmithJ Gustav SmithJonathan D SmithNicholas L SmithElsayed Z SolimanNona SotoodehniaBruno H StrickerAlbert SunHan SunJesper Hastrup SvendsenToshihiro TanakaKahraman TanriverdiKent D TaylorMaris Teder-LavingAlexander TeumerSébastien ThériaultStella TrompetNathan R TuckerArnljot TveitAndre G UitterlindenPim van der HarstIsabelle C Van GelderDavid R Van WagonerNiek VerweijEfthymia VlachopoulouUwe VölkerBiqi WangPeter E WeekeBob WeijsRaul WeissStefan WeissQuinn S WellsKerri L WigginsJorge A WongDaniel WooBradford B WorrallPil-Sung YangJie YaoZachary T YonedaTanja ZellerLingyao ZengSteven A LubitzKathryn L LunettaPatrick T EllinorPublished in: Nature genetics (2018)
Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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