biostudies-literatureGarcia-Marin LMNIBIB NIH HHSNIA NIH HHSNHLBI NIH HHSNINDS NIH HHS2333-2344https://www.ebi.ac.uk/biostudies/studies/S-EPMC12088653biostudies-literatureUnknown56(11)Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and 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 signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestNature geneticsGenomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.PMC12088653P30 AG072975P30 AG072976U01 AG068221P30 AG066530P30 AG010133R56 AG058854RF1 NS136995U54 EB020403R01 AG019771R01 HL105756R01 AG059874Kahn 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 SLBoks MPMIkram MKHimali JJCeja ZKanai RWalter HManiega SMWestlye LTStein JLBeiser ASWestman EHolmes AJMuller-Myhsok BMartinot JLMaillard PVinke LNLin HGrasby KLCalhoun VDFletcher Evan Bokhoven HBastin MEAlhusaini SVernooij MWGruber ORabinowitz JAArias-Vasquez ADiaz-Torres SArfanakis KMirza-Schreiber NSchwarz EPandolfo MWhite TFranke BMattay VSToga AWSatizabal CLPenninx BWJHCampos AIFleischman DABrouwer RMRisacher SLSamann PGSmith AVNyquist PASteen VMFrancks CRenteria MEBoomsma DIFernandez GBuitelaar JKKlein MKnol MJMilaneschi YLiewald DCMBis JCOosterlaan JSchmaal LBennett DASchofield PRStein DJAgartz IDale AMGarcia-Marin LMPausova ZTrollor JNRotter JIAmes DHilal SMitchell BLJack CRGroenewold NALopez OLLawrie SMShin JNothen MMAmouyel PSmoller JWWen WSchmidt HEhrlich SAndreassen OAGe THibar DPFisher SENiessen WJvan T Ent DMedland 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 PHvan der Wee NJAHaukvik UKDesrivieres SSachdev PSChakravarty MHofer ERietschel MDde Geus EJCVillringer ASargurupremraj MHeinz ABurkhardt RGrimm OWolf CForstner 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 JMLongstreth 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. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and 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 signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancest2024-01-01T00:00:00Z2024 Nov2026-06-05T07:34:24.043Z2026-05-14T03:12:28.634ZS-EPMC120886533943388910.1038/s41588-024-01951-z