Shared genetic architecture of cortical morphology and psychiatric disorders: insights from a cross-trait analyses across 180 cortical regions

Abstract

The shared genetic liability between cortical morphology and psychiatric disorders remains unclear. We aimed to identify whether the genetic loci shared between cortical morphology and six psychiatric disorders show regional or global effects. We identified substantial pairwise genetic overlaps of cortical surface area or thickness with psychiatric disorders; however, these loci lacked a uniform direction ([~]50% concordance). Cross-trait analyses revealed distinct architectures: internalizing disorders and schizophrenia/bipolar disorder shared more genetic loci with localized effects, whereas neurodevelopmental disorders shared fewer loci but more with widespread effects. We identified 17 genomic loci shared across all disorders, most of which had opposing directional effects across cortical regions. Only one locus (rs2431112) had region-specific and unidirectional effects (reduced primary visual and posterior cingulate surface area). This directional heterogeneity within and across pleiotropic loci reveals complex shared genetic architectures and likely limits the genetic predictive performance of brain morphology for psychiatric disorders.