biostudies-literatureUnknownGarcia-Marin LMNIA NIH HHSNIMH NIH HHSNHLBI NIH HHSNLM NIH HHSNINDS NIH HHSNIH HHSSubcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signalling and brain ageing-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We medRxiv : the preprint server for health sciences2024.08.13.24311922https://www.ebi.ac.uk/biostudies/studies/S-EPMC11451674biostudies-literatureGenomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.PMC11451674R01 MH117601P30 AG010133S10 OD032285U19 AG024904R01 AG057739R01 AG068193U01 AG068057R01 AG019771R01 MH134004U19 AG074879T32 AG071444U01 AG072177P30 AG072976P30 AG072972RF1 NS136995R01 LM013463R01 HL105756Kahn RSShen LArmstrong NJPsaty BMHoekstra PJMartin NGVolzke HValdes-Hernandez MCCichon SMarquand AFGudnason VRoshchupkin GVFilippi IMcMahon KLHoehn DFMosley THVazquez-Bourgon JDeCarli CChing CRKEspeseth TCrespo-Facorro BIkram MAGrabe HJAthanasiu LHoffmann WHellard SLIkram MKHimali JJde Geus EJCeja ZKanai RWalter HWestlye LTStein JLBeiser ASWestman EHolmes AJMuller-Myhsok BMartinot JLMaillard PVinke LNLin HGrasby KLCalhoun VDFletcher Evan Bokhoven Hvan 't Ent DBastin MEAlhusaini SVernooij MWGruber ORabinowitz JADiaz-Torres SArfanakis KMirza-Schreiber NSchwarz EPandolfo MWhite TFranke BMattay VSToga AWSatizabal CLCampos AIFleischman DALiewald DCBrouwer RMRisacher SLSamann PGSmith AVNyquist PAPenninx BWSteen VMFrancks CRenteria MEBoomsma DIFernandez GBuitelaar JKKlein MKnol MJMilaneschi YVasquez AABis JCOosterlaan JSchmaal LBennett DASchofield PRStein DJAgartz IDale AMGarcia-Marin LMPausova ZTrollor JNRotter JIAmes DHilal SMitchell BLJack CRGroenewold NALopez OLMunoz Maniega SLawrie SMShin JNothen MMAmouyel PSmoller JWWen WSchmidt HEhrlich SAndreassen OAGe THibar DPFisher SENiessen WJMedland SESchmidt RGreen RCCarmichael OTTordesillas-Gutierrez DChen QYang JDepondt CReppermund SCrivello FHosten NSoininen HSThorp JGMelle IDebette Sde Zubicaray GIGoldman ALLi SZwiers MPWeiner MWWitte AVThompson PMFornage MNho KSchumann GLee PHHaukvik UKDesrivieres SSachdev PSChakravarty MHofer ERietschel MDVillringer ASargurupremraj MHeinz ABurkhardt RGrimm OWolf CBoks MPForstner AJMecocci PDjurovic SRomero-Garcia RSaremi AMeyer-Lindenberg ABrodaty HPike GBHaberg AKLuciano MMuhleisen TWNauck MRomanczuk-Seiferth NLemaitre HDe Jager PLSaykin AJScholz MJahanshad NVeltman DJHomuth GCahn WPutz BSisodiya SMWardlaw JMvan der Wee NJLongstreth WTSeshadri SErk SIpser JCSmith GDPaus THo BCMather KALauner LJThomopoulos SIvan der Meer DWeinberger DRJonsson EGfalseGenomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signalling and brain ageing-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We 2024-01-01T00:00:00Z2024 Aug2026-05-14T03:19:51.128Z2025-04-03T23:23:39.448ZS-EPMC114516743937112510.1101/2024.08.13.24311922