Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.

Christian R MarshallDaniel P HowriganDaniele MericoBhooma ThiruvahindrapuramWenting WuDouglas S GreerDanny AntakiAniket ShettyPeter A HolmansDalila PintoMadhusudan GujralWilliam M BrandlerDheeraj MalhotraZhouzhi WangKarin V Fuentes FajaradoMichelle S MaileStephan RipkeIngrid AgartzMargot AlbusMadeline AlexanderFarooq AminJoshua AtkinsSilviu A BacanuRichard A BelliveauSarah E BergenMarcelo BertalanElizabeth BevilacquaTim B BigdeliDonald W BlackRichard BruggemanNancy G BuccolaRandy L BucknerBrendan Bulik-SullivanWilliam ByerleyWiepke CahnGuiqing CaiMurray J CairnsDominique CampionRita M CantorVaughan J CarrNoa CarreraStanley V CattsKimberley D ChambertWei ChengClaude Robert CloningerDavid CohenPaul CormicanNick CraddockBenedicto Crespo-FacorroJames J CrowleyDavid CurtisMichael DavidsonKenneth L DavisFranziska DegenhardtJurgen Del FaveroLynn E DeLisiDimitris DikeosTimothy DinanSrdjan DjurovicGary DonohoeElodie DrapeauJubao DuanFrank DudbridgePeter EichhammerJohan ErikssonValentina Escott-PriceLaurent EssiouxAyman H FanousKai-How FarhMartilias S Farrell Joseph Frank Lude H FrankeRobert FreedmanNelson A FreimerJoseph I FriedmanAndreas J ForstnerMenachem FromerGiulio GenoveseLyudmila GeorgievaElliot S GershonIna GieglingPaola Giusti-RodríguezStephanie GodardJacqueline I GoldsteinJacob GrattenLieuwe de HaanMarian L HamshereMark HansenThomas Folkmann HansenVahram HaroutunianAnnette M HartmannFrans A HenskensStefan HermsJoel N HirschhornPer HoffmannAndrea HofmanHailiang HuangMasashi IkedaInge JoaAnna K KählerRené S KahnLuba KalaydjievaJuha KarjalainenDavid KavanaghMatthew C KellerBrian J KellyJames L KennedyYunjung KimJames A Knowles Bettina KonteClaudine LaurentPhil LeeS Hong LeeSophie E LeggeBernard LererDeborah L LevyKung-Yee LiangJeffrey LiebermanJouko LönnqvistCarmel M LoughlandPatrik K E MagnussonBrion S MaherWolfgang MaierJacques MalletManuel MattheisenMorten MattingsdalRobert W McCarleyColm McDonaldAndrew M McIntoshSandra MeierCarin J MeijerIngrid MelleRaquelle I Mesholam-GatelyAndres MetspaluPatricia T MichieLili A MilaniVihra MilanovaYounes MokrabDerek W MorrisBertram Müller-MyhsokKieran C MurphyRobin M MurrayInez Myin-GermeysIgor NenadicDeborah A NertneyGerald NestadtKristin K NicodemusLaura NisenbaumAnnelie NordinEadbhard O'CallaghanColm O'DushlaineSang-Yun OhAnn OlincyLine OlsenF Anthony O'NeillJim Van OsChristos PantelisGeorge N PapadimitriouElena ParkhomenkoMichele T PatoTiina Paunionull nullDiana O PerkinsTune H PersOlli PietiläinenJonathan PimmAndrew J PocklingtonJohn PowellAlkes PriceAnn E PulverShaun M PurcellDigby QuestedHenrik B RasmussenAbraham ReichenbergMark A ReimersAlexander L RichardsJoshua L RoffmanPanos RoussosDouglas M RuderferVeikko SalomaaAlan R SandersAdam SavitzUlrich SchallThomas G SchulzeSibylle G SchwabEdward M ScolnickRodney J ScottLarry J SeidmanJianxin ShiJeremy M SilvermanJordan W SmollerErik SödermanChris C A SpencerEli A StahlEric StrengmanJana StrohmaierT Scott StroupJaana SuvisaariDragan M SvrakicJin P SzatkiewiczSrinivas ThirumalaiPaul A TooneyJuha VeijolaPeter M VisscherJohn WaddingtonDermot WalshBradley T WebbMark WeiserDieter B WildenauerNigel M WilliamsStephanie WilliamsStephanie H WittAaron R WolenBrandon K WormleyNaomi R WrayJing Qin WuClement C ZaiRolf AdolfssonOle A AndreassenDouglas H R BlackwoodElvira BramonJoseph D BuxbaumSven CichonDavid A CollierAiden CorvinMark J DalyAriel DarvasiEnrico DomeniciTõnu EskoPablo V GejmanMichael GillHugh GurlingChristina M HultmanNakao IwataAssen V JablenskyErik G JönssonKenneth S KendlerGeorge KirovJo KnightDouglas F LevinsonQingqin S LiSteven A McCarrollAndrew McQuillinJennifer L MoranBryan J MowryMarkus M NöthenRoel A OphoffMichael J OwenAarno PalotieCarlos N PatoTracey L PetryshenDanielle PosthumaMarcella RietschelBrien P RileyDan RujescuPamela SklarDavid St ClairJames T R WaltersThomas WergePatrick F SullivanMichael C O'DonovanStephen W SchererBenjamin M NealeJonathan Sebatnull null

Published in: Nature genetics (2016)

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

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