biostudies-literatureBledsoe XScott Hamilton CARES FoundationNIA NIH HHSNHGRI NIH HHSNIH HHSNIGMS NIH HHSe71217https://www.ebi.ac.uk/biostudies/studies/S-EPMC12930104biostudies-literatureUnknown22(2)<h4>Introduction</h4>Neuroimaging genetics has advanced our understanding of Alzheimer's disease (AD); however, frameworks using functional genomics are needed to elucidate mechanisms connecting loci to neurological outcomes. To address this need, we explored relationships between AD-associated variants and disease via their impact on gene expression and neuroanatomical phenotypes.<h4>Methods</h4>We mapped established AD genes to neuroimaging traits using the NeuroimaGene Atlas and predicted transcript-driven neurological features of AD by comparing gene-derived neuroimaging features with clinical neuroimaging data. Genetic covariance analyses were performed to characterize shared genetic architecture between AD endophenotypes and neuroimaging features, and to identify neuroimaging featureAlzheimer's & dementia : the journal of the Alzheimer's AssociationNeuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's disease.PMC12930104R01HG011138R01AG073439RF1AG061351R35HG010718R56AG068026R01GM140287Dumitrescu LBush WSGamazon ERChen HHNaj ACBelow JEArcher DWang TCBledsoe XWu YHohman TJfalseNeuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's disease.<h4>Introduction</h4>Neuroimaging genetics has advanced our understanding of Alzheimer's disease (AD); however, frameworks using functional genomics are needed to elucidate mechanisms connecting loci to neurological outcomes. To address this need, we explored relationships between AD-associated variants and disease via their impact on gene expression and neuroanatomical phenotypes.<h4>Methods</h4>We mapped established AD genes to neuroimaging traits using the NeuroimaGene Atlas and predicted transcript-driven neurological features of AD by comparing gene-derived neuroimaging features with clinical neuroimaging data. Genetic covariance analyses were performed to characterize shared genetic architecture between AD endophenotypes and neuroimaging features, and to identify neuroimaging feature2026-01-01T00:00:00Z2026 Feb2026-07-16T20:26:14.192Z2026-07-10T03:10:39.704ZS-EPMC129301044173210810.1002/alz.71217