6533b86efe1ef96bd12cb6a4

RESEARCH PRODUCT

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Anita ThaparLena BacklundLindsey KentWalter J. MuirWalter J. MuirA. Jeremy WillseySandra K. LooMichael BoehnkeChrista Lese MartinAnia KorszunGuiomar OliveiraVeronica J. VielandStephen W. SchererRené S. KahnDarina CzamaraJeremy R. ParrMichael E. GoddardWillem A. NolenJosep Antoni Ramos-quirogaStephen SandersKarola RehnstroemNelson B. FreimerErin N. SmithAnn OlincyIngrid MelleMyrna M. WeissmanJames A. KnowlesWilliam ByerleyAravinda ChakravartiShaun PurcellJens TreutleinSebastian ZoellnerHakon HakonarsonSusanne LucaeMarkus M. NoethenIan B. HickieMarion FriedlSrinivasa ThirumalaiStephen NewhouseJoseph PivenAndrew M. McintoshCathryn M. LewisSrdjan DjurovicFrancis J. McmahonAyman H. FanousAyman H. FanousBernie DevlinSteven A. MccarrollAlan F. SchatzbergPeter SzatmariPeter SzatmariMarta RibasésC. Robert CloningerBrenda W.j.h. PenninxGerard Van GrootheestPhil LeeRichard AnneyElaine K. GreenGeraldine DawsonJoseph A. SergeantDigby QuestedMagdalena GrossJack D. BarchasNicholas G. MartinTimothy W. YuJouke-jan HottengaMark LathropFederica TozziMartin HautzingerAlysa E. DoyleCinnamon S. BlossCinnamon S. BlossSandra MeierLouise GailagherDavid A. CollierFarooq AminMichael C. NealeMartin SchallingLieuwe De HaanBru CormandFalk W. LohoffJennifer CrosbieHoward J. EdenbergAarno PalotieJohannes H. SmitRobert FreedmanKatherine Gordon-smithMichele L. PergadiaEnda M. ByrneHans-christoph SteinhausenHans-christoph SteinhausenBenjamin M. NealeBenjamin M. NealeAnjali K. HendersMichele T. PatoManuel MattheisenManuel MattheisenUrban ÖSbyEdward M. ScolnickEvaristus A. NwuliaFritz PoustkaGonneke WillemsenAndrew C. HeathDavid St. CairEmma M. QuinnI. Nicol FerrierJohn R. KelsoeVanessa HusAndrew McquillinJohn P. RiceWilliam M. McmahonJoseph BiedermanDanyu LinWolfgang MaierFrans G. ZitmanJosephine EliaNicholas J. SchorkStéphane JamainLizzy RossinJubao DuanJubao DuanIngrid AgartzDevin AbsherJordan W. SmollerMatthew W. StateRichard M. MyersShrikant ManeCarlos N. PatoWilliam E. BunneyMarian L. HamshereManfred UhrNicholas John CraddockAstrid M. VicenteTobias BanaschewskiDavid CurtisAnne FarmerScott D. GordonAnna K. KaehlerEric M. MorrowMarcella RietschelPatrik K. E. MagnussonKlaus-peter LeschRebecca MckinneyJana StrohmaierThomas F. WienkerPablo V. GejmanPablo V. GejmanDouglas BlackwoodMaria Helena Pinto De AzevedoTiffany A. GreenwoodDon H. LinszenDaniel L. KollerRichard BruggemanVinay PuriNaomi R. WrayStanley J. WatsonElena MaestriniValentina MoskvinaFrank DudbridgeDanielle PosthumaDanielle PosthumaEdward G. JonesEdward G. JonesLambertus KleiSarah E. BergenFan MengSteven P. HamiltonGuy A. RouleauPierandrea MugliaMikael LandénMikael LandénStephanie H. WittLaramie E. DuncanLaramie E. DuncanStanley ZammitJudith A. BadnerFlorian HolsboerEco J. C. De GeusDaniel Moreno-de-lucaBenjamin S. PickardBenjamin S. PickardGunnar MorkenMichael Conlon O'donovanMichael SteffensKathryn RoederDorret I. BoomsmaPaul D. ShillingStephan RipkeStephan RipkeNigel WilliamsJeremy M. SilvermanDavid CraigMark J. DalyMichael BauerDetelina GrozevaMarkus J. SchwarzPeter HolmansHugh GurlingT. Scott StroupAribert RothenbergerGary DonohoeEric FombonneJoseph D. BuxbaumMatthew FlicldngerBryan J. MowryThomas HansenThomas HansenIna GieglingGrant W. MontgomeryCaroline M. NievergeltSusan L. SmalleyJung-ying TzengDavid H. LedbetterChristopher A. WalshChristopher A. WalshGerard D. SchellenbergSarah E. MedlandRobert D. OadesJames B. PotashDan E. ArkingJohannes SchumacherMichael GillJames J. McgoughJennifer L. MoranDonald W. BlackSian CaesarNeelroop N. ParikshakIan W. CraigSabine M. KlauckWade H. BerrettiniT. ForoudPeter P. ZandiInez Myin-germeysMarcus IsingSven CichonSven CichonAlexandre A. TodorovMònica BayésThomas WergeSusan L. SlagerStanley I. ShynJim Van OsDerek W. MorrisDouglas M. RuderferThomas W. MuehleisenMatthew C. KellerSusmita DattaIan JonesJohn B. VincentJames L. KennedyAnthony P. MonacoAnthony P. MonacoJianxin ShiDale R. NyholtBruno EtainChristine FraserPaul CormicanMiguel CasasRadhika KandaswamyGerome BreenStephen V. FaraoneJonna KuntsiThomas BetteckenWitte J.g. HoogendijkNancy G. BuccolaFranziska DegenhardtLyudmila GeorgievaMarion LeboyerAlan R. SandersAlan R. SandersJohn StraussDan RujescuRussell SchacharHelena MedeirosLisa JonesPeter M. VisscherLauren A. WeissRené BreuerJohn I. NurnbergerAndreas ReifPhoenix KwanVihra MilanovaChunyu LiuMartin A. KohliDonald J. MacintyreDonald J. MacintyreNicholas BassKhalid ChoudhuryEdwin H. CookCatherine LordAndrew D. PatersonJobst MeyerRichard P. EbsteinZhaoming ZhaoNiklas LaengstroemThomas G. SchulzeThomas G. SchulzePeter ProppingWei XuRobert C. ThompsonKimberly ChambertJonathan PimmIvan NikolovPamela A. F. MaddenKevin A. McgheeJacob LawrenceJan K. BuitelaarAndres IngasonAndres IngasonChristine M. FreitagRobert KrasuckiWiepke CahnRita M. CantorChristina M. HultmanMelvin G. McinnisCatalina BetancurCatalina BetancurEftichia DuketisMichael T. MurthaThomas H. WassinkPhilip AshersonJohn S. WitteElaine KennyEdmund J.s. Sonuga-barkeLydia KrabbendamLine OlsenLine OlsenAgatino BattagliaLaura J. ScottAnnette M. HartmannYunjung KimRichard O. DayEdwin J. C. G. Van Den OordOle A. AndreassenHerbert RoeyersMichael John OwenColm O'dushlainePeng ZhangMorten MattingsdalMichael L. CuccaroMargaret A. Pericak-vanceJoachim HallmayerJun LiPamela B. MahonElisabeth B. BinderWilliam A. ScheftnerDaniel H. GeschwindChristel M. MiddeldorpJosef FrankKeith MatthewsJennifer K. LowePaul LichtensteinVerneri AnttilaPamela SklarSzabocls SzelingerRoel A. OphoffPeter McguffinStefan HermsStefan HermsBettina KonteGeorge KirovHilary CoonMaria HipolitoLouise FrisénKenneth S. KendlerFrank BellivieridJames S. SutdiffeJeffrey A. LiebermanTodd LenczSusanne HoefelsAlan W. McleanAlan W. McleanBarbara FrankeHuda AkilSoumya RaychaudhuriEllen M. WijsmanVishwajit L. NimgaonkarRoy H. PerlisRoy H. PerlisPatrick J. McgrathSusan L. SantangeloWilliam CoryellHenrik B. RasmussenHenrik B. RasmussenWeihua GuanWeihua GuanWilliam LawsonElliot S. GershonSean EnnisAiden CorvinAllan H. YoungThomas B. BarrettJonathan L. HainesDouglas F. LevinsonAna MirandaAnil K. MalhotraS. Hong LeeStan F. NelsonAnthony J. BaileyPatrick F. SullivanDorothy E. GriceLefkos T. MiddletonBertram Mueller-myhsokMichael R. BarnesAdebayo Anjorin

subject

Netherlands Twin Register (NTR)Statistical methodsAutismMedizinLOCIGenome-wide association studyheritabilityGenome-wide association studiesHistonesGenètica mèdica0302 clinical medicineHistone methylationDatabases Genetic2.1 Biological and endogenous factorsPsychologyGWASAetiologyPsychiatric geneticsR2Cbipolar disorderPsychiatry0303 health sciencesDisordersLociDepressionGeneral NeuroscienceMental DisordersMedical geneticsMETHYLATIONBrain3rd-DASSerious Mental IllnessPsychiatric Disorders3. Good healthHistoneMental HealthSchizophreniaMental DisorderCognitive Sciences[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]PromotersBDCBURDENRC0321 Neuroscience. Biological psychiatry. NeuropsychiatryHumanSignal Transductionmedicine.medical_specialtyDISORDERSGenomicsNetwork and Pathway Analysis Subgroup of Psychiatric Genomics ConsortiumBurdenBiologyMethylationArticleBiological pathwayPROMOTERS03 medical and health sciencesDatabasesGeneticmedicineGenetics/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_HumansGenetic Predisposition to Diseasehistone methylationBipolar disorderPsiquiatriaAUTISMPsychiatry030304 developmental biologyGenetic associationNeurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]Neurology & NeurosurgeryNeuroscience (all)Human GenomeNeurosciencesmedicine.diseaseBrain DisordersGood Health and Well BeingDE-NOVO MUTATIONSPerturbações do Desenvolvimento Infantil e Saúde MentalRC0321SchizophreniaGenome-wide Association StudiesDe-novo mutationsmajor depressionNeuroscience030217 neurology & neurosurgeryGenome-Wide Association Study

description

G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. Postprint Peer reviewed

yearjournalcountryeditionlanguage
2015-02-01
https://hdl.handle.net/1887/101566