Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
Stephan RipkeColm O'DushlaineKimberly ChambertJennifer L MoranAnna K KählerSusanne AkterinSarah E BergenAnn L CollinsJames J CrowleyMenachem FromerYunjung KimSang Hong LeePatrik K E MagnussonNick SanchezEli A StahlStephanie WilliamsNaomi R WrayKai XiaFrancesco BettellaAnders D BorglumBrendan K Bulik-SullivanPaul CormicanNick CraddockChristiaan de LeeuwNaser DurmishiMichael GillVera GolimbetMarian L HamsherePeter HolmansDavid M HougaardKenneth S KendlerKuang LinDerek W MorrisOle MorsPreben B MortensenBenjamin M NealeFrancis A O'NeillMichael J OwenMilica Pejovic MilovancevicDanielle PosthumaJohn PowellAlexander L RichardsBrien P RileyDouglas RuderferDan RujescuEngilbert SigurdssonTeimuraz SilagadzeAugust B SmitHreinn StefanssonStacy SteinbergJaana SuvisaariSarah TosatoMatthijs VerhageJames T Waltersnull nullDouglas F LevinsonPablo V GejmanKenneth S KendlerClaudine LaurentBryan J MowryMichael C O'DonovanMichael J OwenAnn E PulverBrien P RileySibylle G SchwabDieter B WildenauerFrank DudbridgePeter HolmansJianxin ShiMargot AlbusMadeline AlexanderDominique CampionDavid CohenDimitris DikeosJubao DuanPeter EichhammerStephanie GodardMark HansenF Bernard LererKung-Yee LiangWolfgang MaierJacques MalletDeborah A NertneyGerald NestadtNadine NortonFrancis A O'NeillGeorge N PapadimitriouRobert RibbleAlan R SandersJeremy M SilvermanDermot WalshNigel M WilliamsBrandon Wormleynull nullMaria J ArranzSteven BakkerStephan BenderElvira BramonDavid CollierBenedicto Crespo-FacorroJeremy HallConrad IyegbeAssen JablenskyRene S KahnLuba KalaydjievaStephen LawrieCathryn M LewisKuang LinDon H LinszenIgnacio MataAndrew McIntoshRobin M MurrayRoel A OphoffJohn PowellDan RujescuJim Van OsMuriel WalsheMatthias WeisbrodDurk Wiersmanull nullPeter DonnellyInes BarrosoJenefer M BlackwellElvira BramonMatthew A BrownJuan P CasasAiden P CorvinPanos DeloukasAudrey DuncansonJanusz JankowskiHugh S MarkusChristopher G MathewColin N A PalmerRobert PlominAnna RautanenStephen J SawcerRichard C TrembathAnanth C ViswanathanNicholas W WoodChris C A SpencerGavin BandCéline BellenguezColin FreemanGarrett HellenthalEleni GiannoulatouMatti PirinenRichard D PearsonAmy StrangeZhan SuDamjan VukcevicPeter DonnellyCordelia LangfordSarah E HuntSarah EdkinsRhian GwilliamHannah BlackburnSuzannah J BumpsteadSerge DronovMatthew GillmanEmma GrayNaomi HammondAlagurevathi JayakumarOwen T McCannJennifer LiddleSimon C PotterRadhi RavindrarajahMichelle RickettsAvazeh Tashakkori-GhanbariaMatthew J WallerPaul WestonSara WidaaPamela WhittakerInes BarrosoPanos DeloukasChristopher G MathewJenefer M BlackwellMatthew A BrownAiden P CorvinMark I McCarthyChris C A SpencerElvira BramonAiden P CorvinMichael C O'DonovanKari StefanssonEdward ScolnickShaun PurcellSteven A McCarrollPamela SklarChristina M HultmanPatrick F SullivanPublished in: Nature genetics (2013)
Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.