Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.

Rainer MalikGanesh ChauhanMatthew TraylorMuralidharan SargurupremrajYukinori OkadaAniket MishraLoes C A Rutten-JacobsAnne-Katrin GieseSander W van der LaanSolveig GretarsdottirChristopher D AndersonMichael ChongHieab H H AdamsTetsuro AgoPeter Almgren Phillippe AmouyelHakan AyTraci M BartzOscar R BenaventeSteve BevanGiorgio B BoncoraglioRobert D BrownAdam S ButterworthCaty CarreraCara L CartyDaniel I ChasmanWei-Min ChenJohn W ColeAdolfo CorreaIoana CotlarciucCarlos CruchagaJohn DaneshPaul I W de BakkerAnita L DeStefanoMarcel den HoedQing DuanStefan T EngelterGuido J FalconeRebecca F GottesmanRaji P GrewalVilmundur GudnasonStefan GustafssonJeffrey HaesslerTamara B HarrisAhamad HassanAki Samuli HavulinnaSusan R HeckbertElizabeth G HollidayGeorge HowardFang-Chi HsuHyacinth I HyacinthMohammad Arfan IkramErik IngelssonMarguerite R IrvinXueqiu JianJordi Jiménez-CondeJulie A JohnsonJohan Wouter Jukema Masahiro KanaiKeith L KeeneBrett M KisselaDawn O KleindorferCharles KooperbergMichiaki KuboLeslie A LangeCarl D LangefeldClaudia LangenbergLenore J LaunerJin-Moo LeeRobin LemmensDidier LeysCathryn M Lewis Wei-Yu LinArne G LindgrenErik LorentzenPatrik K E MagnussonJane MaguireAni ManichaikulPatrick F McArdleJames F MeschiaBraxton D MitchellThomas H MosleyMichael A NallsToshiharu NinomiyaMartin J O'DonnellBruce M PsatySara L PulitKristiina RannikmäeAlexander P ReinerKathryn M RexrodeKenneth RiceStephen S RichPaul M RidkerNatalia S RostPeter M RothwellJerome I RotterTatjana RundekRalph L SaccoSaori SakaueMichele M SaleVeikko SalomaaBishwa R SapkotaReinhold SchmidtCarsten O SchmidtUlf SchminkePankaj SharmaAgnieszka SlowikCathie L M SudlowChristian TanislavTurgut TatlisumakKent D TaylorVincent N S ThijsGudmar ThorleifssonUnnur ThorsteinsdottirSteffen TiedtStella TrompetChristophe TzourioCornelia M van DuijnMatthew WaltersNicholas J WarehamSylvia Wassertheil-SmollerJames G WilsonKerri L Wiggins Qiong YangSalim Yusufnull nullnull nullnull nullnull nullnull nullJoshua C BisTomi PastinenArno RuusaleppEric E Schadt Simon KoplevJohan L M BjörkegrenVeronica CodoniMete CivelekNicholas L SmithDavid Alexandre Trégouët Ingrid E Christophersen Carolina RoselliSteven A LubitzPatrick T EllinorE Shyong TaiJaspal S KoonerNorihiro KatoJiang HePim van der Harst Paul ElliottJohn C ChambersFumihiko TakeuchiAndrew D Johnsonnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullnull nullDharambir K SangheraOlle MelanderChristina JernDaniel StrbianIsrael Fernandez-CadenasW T LongstrethArndt RolfsJun HataDaniel WooJonathan RosandGuillaume PareJemma C HopewellDanish SaleheenKari StefanssonBradford B WorrallSteven J KittnerSudha SeshadriMyriam FornageHugh S MarkusJoanna M M HowsonYoichiro KamataniStephanie DebetteMartin Dichgans

Published in: Nature genetics (2018)

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

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