Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.
Naomi R WrayStephan RipkeManuel MattheisenMaciej TrzaskowskiEnda M ByrneAbdel AbdellaouiMark J AdamsEsben AgerboTracy M AirTill M F AndlauerSilviu-Alin BacanuMarie Bækvad-HansenAartjan F T BeekmanTim B BigdeliElisabeth B BinderDouglas R H BlackwoodJulien BryoisHenriette N ButtenschønJonas Bybjerg-GrauholmNa CaiEnrique CastelaoJane Hvarregaard ChristensenToni-Kim ClarkeJonathan I R ColemanLucía Colodro-CondeBaptiste Couvy-DuchesneNick CraddockGregory E CrawfordCheynna A CrowleyHassan S DashtiGail DaviesIan J DearyFranziska DegenhardtEske M DerksNese DirekConor V DolanErin C DunnThalia C EleyNicholas ErikssonValentina Escott-PriceFarnush Hassan Farhadi KiadehHilary K FinucaneAndreas J ForstnerJosef FrankHéléna A GasparMichael GillPaola Giusti-RodríguezFernando S GoesScott D GordonJakob GroveLynsey S HallEilis HannonChristine Søholm HansenThomas F HansenStefan HermsIan B HickiePer HoffmannGeorg HomuthCarsten HornJouke-Jan HottengaDavid M HougaardMing HuCraig L HydeMarcus IsingRick JansenFulai JinEric JorgensonJames A KnowlesIsaac S KohaneJulia KraftWarren W KretzschmarJesper KroghZoltán KutalikJacqueline M LaneYihan LiYun LiPenelope A LindXiaoxiao LiuLeina LuDonald J MacIntyreDean F MacKinnonRobert M MaierWolfgang MaierJonathan MarchiniHamdi MbarekPatrick McGrathPeter McGuffinSarah E MedlandDivya MehtaChristel M MiddeldorpEvelin MihailovYuri MilaneschiLili MilaniJonathan MillFrancis M MondimoreGrant W MontgomerySara MostafaviNiamh MullinsMatthias NauckBernard NgMichel G NivardDale R NyholtPaul F O'ReillyHogni OskarssonMichael J OwenJodie N PainterCarsten Bøcker PedersenMarianne Giørtz PedersenRoseann E PetersonErik PetterssonWouter J PeyrotGiorgio PistisDanielle PosthumaShaun M PurcellJorge A QuirozPer QvistJohn P RiceBrien P RileyMargarita RiveraSaira Saeed MirzaRicha SaxenaRobert SchoeversEva C SchulteLing ShenJianxin ShiStanley I ShynEngilbert SigurdssonGrant B C SinnamonJohannes H SmitDaniel J SmithHreinn StefanssonStacy SteinbergCraig A StockmeierFabian StreitJana StrohmaierKatherine E TanseyHenning TeismannAlexander TeumerWesley ThompsonPippa A ThomsonThorgeir E ThorgeirssonChao TianMatthew TraylorJens TreutleinVassily TrubetskoyAndré G UitterlindenDaniel UmbrichtSandra Van der AuweraAlbert M van HemertAlexander ViktorinPeter M VisscherYunpeng WangBradley T WebbShantel Marie WeinsheimerJürgen WellmannGonneke WillemsenStephanie H WittYang WuHualin S XiJian YangFutao Zhangnull nullnull nullVolker AroltBernhard T BauneKlaus BergerDorret I BoomsmaSven CichonUdo DannlowskiE C J de GeusJ Raymond DePauloEnrico DomeniciKatharina DomschkeTõnu EskoHans J GrabeSteven P HamiltonCaroline HaywardAndrew C HeathDavid A HindsKenneth S KendlerStefan KloiberGlyn LewisQingqin S LiSusanne LucaePamela F A MaddenPatrik K MagnussonNicholas G MartinAndrew M McIntoshAndres MetspaluOle MorsPreben Bo MortensenBertram Müller-MyhsokMerete NordentoftMarkus M NöthenMichael C O'DonovanSara A PacigaNancy L PedersenBrenda W J H PenninxRoy H PerlisDavid J PorteousJames B PotashMartin PreisigMarcella RietschelCatherine SchaeferThomas G SchulzeJordan W SmollerKari StefanssonHenning TiemeierRudolf UherHenry VölzkeMyrna M WeissmanThomas WergeAshley R WinslowCathryn M LewisDouglas F LevinsonGerome BreenAnders D BørglumPatrick F Sullivannull nullPublished in: Nature genetics (2018)
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.