Analysis of shared heritability in common disorders of the brain.
null nullVerneri AnttilaBrendan Bulik-SullivanHilary K FinucaneRaymond K WaltersJose BrasLaramie E DuncanValentina Escott-PriceGuido J FalconePadhraig GormleyRainer MalikNikolaos A PatsopoulosStephan RipkeZhi WeiDongmei YuPhil H LeePatrick TurleyBenjamin Grenier-BoleyVincent ChourakiYoichiro KamataniClaudine BerrLuc LetenneurDidier HannequinPhilippe AmouyelAnne BolandJean-François DeleuzeEmmanuelle DuronBadri N VardarajanChristiane ReitzAlison M GoateMatthew J HuentelmanM Ilyas KambohEric B LarsonEkaterina RogaevaPeter St George-HyslopHakon HakonarsonWalter A KukullLindsay A FarrerLisa L BarnesThomas G BeachF Yesim DemirciElizabeth HeadChristine M HuletteGregory A JichaJohn S K KauweJeffrey A KayeJames B LeverenzAllan I LeveyAndrew P LiebermanVernon S PankratzWayne W PoonJoseph F QuinnAndrew J SaykinLon S SchneiderAmanda G SmithJoshua A SonnenRobert A SternVivianna M Van DeerlinLinda J Van EldikDenise HaroldGiancarlo RussoDavid C RubinszteinAnthony BayerMagda TsolakiPetra ProitsiNick C FoxHarald HampelMichael J OwenSimon MeadPeter PassmoreKevin MorganMarkus M NöthenMartin RossorMichelle K LuptonPer HoffmannJohannes KornhuberBrian LawlorAndrew McQuillinAmmar Al-ChalabiJoshua C BisAgustin RuizMercè BoadaSudha SeshadriAlexa BeiserKenneth RiceSven J van der LeePhilip L De JagerDaniel H GeschwindMatthias RiemenschneiderSteffi Riedel-HellerJerome I RotterGerhard RansmayrBradley T HymanCarlos CruchagaMontserrat AlegretBendik WinsvoldPriit PaltaKai-How FarhEster Cuenca-LeonNicholas FurlotteTobias KurthLannie LigthartGisela M TerwindtTobias FreilingerCaroline RanScott D GordonGuntram BorckHieab H H AdamsTerho LehtimäkiJuho WedenojaJulie E BuringMarkus SchürksMaria HrafnsdottirJouke-Jan HottengaBrenda PenninxVille ArttoMari KaunistoSalli VepsäläinenNicholas G MartinGrant W MontgomeryMitja I KurkiEija HämäläinenHailiang HuangJie HuangCynthia SandorCaleb WebberBertram Muller-MyhsokStefan SchreiberVeikko SalomaaElizabeth LoehrerHartmut GöbelAlfons MacayaPatricia Pozo-RosichThomas HansenThomas WergeJaakko KaprioAndres MetspaluChristian KubischMichel D FerrariAndrea C BelinArn M J M van den MaagdenbergJohn-Anker ZwartDorret BoomsmaNicholas ErikssonJes OlesenDaniel I ChasmanDale R NyholtAndreja AvbersekLarry BaumSamuel BerkovicJonathan BradfieldRussell J BuonoClaudia B CatarinoPatrick CossettePeter De JongheChantal DepondtDennis DlugosThomas N FerraroJacqueline FrenchHelle HjalgrimJennifer Jamnadas-KhodaReetta KälviäinenWolfram S KunzHolger LercheCostin LeuDick LindhoutWarren LoDaniel LowensteinMark McCormackRikke S MøllerAnne MolloyPing-Wing NgKaren OliverMichael PriviteraRodney RadtkeAnn-Kathrin RuppertThomas SanderSteven SchachterChristoph SchankinIngrid SchefferSusanne SchochSanjay M SisodiyaPhilip SmithMichael SperlingPasquale StrianoRainer SurgesG Neil ThomasFrank VisscherChristopher D WhelanFederico ZaraErin L HeinzenAnthony MarsonFelicitas BeckerHans StroinkFritz ZimprichThomas GasserRaphael GibbsPeter HeutinkMaria MartinezHuw R MorrisManu SharmaMina RytenKin Y MokSara PulitSteve BevanElizabeth HollidayJohn AttiaThomas BatteyGiorgio BoncoraglioVincent ThijsWei-Min ChenBraxton MitchellPeter RothwellPankaj SharmaCathie SudlowAstrid VicenteHugh MarkusChristina KourkoulisJoana PeraMiriam RaffeldScott SillimanVesna Boraska PericaLaura M ThorntonLaura M HuckinsN William RaynerCathryn M LewisMonica GratacosFilip RybakowskiAnna Keski-RahkonenAnu RaevuoriJames I HudsonTed Reichborn-KjennerudPalmiero MonteleoneAndreas KarwautzKatrin MannikJessica H BakerJulie K O'TooleSara E TraceOliver S P DavisSietske G HelderStefan EhrlichBeate Herpertz-DahlmannUnna N DannerAnnemarie A van ElburgMaurizio ClementiMonica ForzanElisa DocampoJolanta LissowskaJoanna HauserAlfonso TortorellaMario MajFragiskos GonidakisKonstantinos TziouvasHana PapezovaZeynep YilmazGudrun WagnerSarah Cohen-WoodsStefan HermsAntonio JuliàRaquel RabionetDanielle M DickSamuli RipattiOle A AndreassenThomas EspesethAstri J LundervoldVidar M SteenDalila PintoStephen W SchererHarald AschauerAlexandra SchosserLars AlfredssonLeonid PadyukovKatherine A HalmiJames MitchellMichael StroberAndrew W BergenWalter KayeJin Peng SzatkiewiczBru CormandJosep Antoni Ramos-QuirogaCristina Sánchez-MoraMarta RibasésMiguel CasasAmaia HervasMaria Jesús ArranzJan HaavikTetyana ZayatsStefan JohanssonNigel WilliamsAstrid DempfleAribert RothenbergerJonna KuntsiRobert D OadesTobias BanaschewskiBarbara FrankeJan K BuitelaarAlejandro Arias VasquezAlysa E DoyleAndreas ReifKlaus-Peter LeschChristine FreitagOlga RiveroHaukur PalmasonMarcel RomanosKate LangleyMarcella RietschelStephanie H WittSoeren DalsgaardAnders D BørglumIrwin WaldmanBeth WilmotNikolas MollyClaiton H D BauJennifer CrosbieRussell SchacharSandra K LooJames J McGoughEugenio H GrevetSarah E MedlandElise RobinsonLauren A WeissElena BacchelliAnthony BaileyVanessa BalAgatino BattagliaCatalina BetancurPatrick BoltonRita CantorPatrícia Celestino-SoperGeraldine DawsonSilvia De RubeisFrederico DuqueAndrew GreenSabine M KlauckMarion LeboyerPat LevittElena MaestriniShrikant ManeDaniel Moreno- De-LucaJeremy ParrRegina ReganAbraham ReichenbergSven SandinJacob VorstmanThomas WassinkEllen WijsmanEdwin CookSusan SantangeloRichard DelormeBernadette RogéTiago MagalhaesDan ArkingThomas G SchulzeRobert C ThompsonJana StrohmaierKeith MatthewsIngrid MelleDerek MorrisDouglas BlackwoodAndrew McIntoshSarah E BergenMartin SchallingStéphane JamainAnna MaaserSascha B FischerCéline S ReinboldJanice M FullertonJosé Guzman-ParraFermin MayoralPeter R SchofieldSven CichonThomas W MühleisenFranziska DegenhardtJohannes SchumacherMichael BauerPhilip B MitchellElliot S GershonJohn RiceJames B PotashPeter P ZandiNick CraddockI Nicol FerrierMartin AldaGuy A RouleauGustavo TureckiRoel OphoffCarlos PatoAdebayo AnjorinEli StahlMarkus LeberPiotr M CzerskiCristiana CruceanuIan R JonesDanielle PosthumaTill F M AndlauerAndreas J ForstnerFabian StreitBernhard T BauneTracy AirGrant SinnamonNaomi R WrayDonald J MacIntyreDavid PorteousGeorg HomuthMargarita RiveraJakob GroveChristel M MiddeldorpIan HickieMichele PergadiaDivya MehtaJohannes H SmitRick JansenEco de GeusErin DunnQingqin S LiMatthias NauckRobert A SchoeversAartjan Tf BeekmanJames A KnowlesAlexander ViktorinPaul ArnoldCathy L BarrGabriel Bedoya-BerrioO Joseph BienvenuHelena BrentaniChristie BurtonBeatriz CamarenaCarolina CappiDanielle CathMaria CavalliniDaniele CusiSabrina DarrowDamiaan DenysEske M DerksAndrea DietrichThomas FernandezMartijn FigeeNelson FreimerGloria GerberMarco GradosErica GreenbergGregory L HannaAndreas HartmannMatthew E HirschtrittPieter J HoekstraAlden HuangChaim HuyserCornelia IllmannMichael JenikeSamuel KupermanBennett LeventhalChristine LochnerGholson J LyonFabio MacciardiMarcos Madruga-GarridoIrene A MalatyAthanasios MarasLauren McGrathEurípedes C MiguelPablo MirGerald NestadtHumberto NicoliniMichael S OkunAndrew PakstisPeristera PaschouJohn PiacentiniChristopher PittengerKerstin PlessenVasily RamenskyEliana M RamosVictor ReusMargaret A RichterMark A RiddleMary M RobertsonVeit RoessnerMaria RosárioJack F SamuelsPaul SandorDan J SteinFotis TsetsosFilip Van NieuwerburghSarah WeatherallJens R WendlandTomasz WolanczykYulia WorbeGwyneth ZaiFernando S GoesNicole McLaughlinPaul S NestadtHans-Jorgen GrabeChristel DepienneAnuar KonkashbaevNuria LanzagortaAna Valencia-DuarteElvira BramonNancy BuccolaWiepke CahnMurray CairnsSiow A ChongDavid CohenBenedicto Crespo-FacorroJames CrowleyMichael DavidsonLynn DeLisiTimothy DinanGary DonohoeElodie DrapeauJubao DuanLieuwe HaanDavid HougaardSena Karachanak-YankovaAndrey KhruninJanis KlovinsVaidutis KučinskasJimmy Lee Chee KeongSvetlana LimborskaCarmel LoughlandJouko LönnqvistBrion MaherManuel MattheisenColm McDonaldKieran C MurphyIgor NenadicJim van OsChristos PantelisMichele PatoTracey PetryshenDigby QuestedPanos RoussosAlan R SandersUlrich SchallSibylle G SchwabKang SimHon-Cheong SoElisabeth StögmannMythily SubramaniamDraga TonchevaJohn WaddingtonJames WaltersMark WeiserWei ChengRobert CloningerDavid CurtisPablo V GejmanFrans HenskensMorten MattingsdalSang-Yun OhRodney ScottBradley WebbGerome D BreenClaire ChurchhouseCynthia M BulikMark J DalyMartin DichgansStephen V FaraoneRita GuerreiroPeter A HolmansKenneth S KendlerBobby P C KoelemanCarol A MathewsAlkes PriceJeremiah ScharfPamela SklarJulie WilliamsNicholas W WoodChris CotsapasAarno PalotieJordan W SmollerPatrick F SullivanJonathan RosandAiden CorvinBenjamin M NealeJonathan M SchottRichard AnneyJosephine EliaMaria Grigoroiu-SerbanescuHoward J EdenbergRobin MurrayPublished in: Science (New York, N.Y.) (2018)
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.