Cross-trait analyses reveal complex genetic overlaps between cortical morphology and psychiatric disorders.

This study utilized cross-trait analyses to investigate genetic loci shared between cortical morphology, including surface area and thickness, and a spectrum of psychiatric disorders. The population and specific sample size were not reported in the provided data. The primary outcome assessed pairwise genetic overlaps between cortical metrics and conditions including schizophrenia, bipolar disorder, internalizing disorders, and neurodevelopmental disorders.

Main results indicated substantial pairwise genetic overlaps, yet these effects lacked a uniform direction, showing roughly 50% concordance. Analysis of genetic loci shared between cortical morphology and internalizing disorders or schizophrenia/bipolar disorder revealed more loci with localized effects. Conversely, fewer loci were shared with neurodevelopmental disorders, but these exhibited more widespread effects. Additionally, 17 genomic loci were identified as shared across all disorders, with most demonstrating opposing directional effects across different cortical regions.

Safety and tolerability data were not reported. A key limitation identified was that directional heterogeneity within and across pleiotropic loci reveals complex shared genetic architectures. This complexity likely limits the genetic predictive performance of brain morphology for psychiatric disorders. Consequently, clinicians should interpret these findings with caution regarding the utility of cortical morphology as a standalone genetic predictor for these conditions.