Contrasting genetic predisposition and diagnosis in psychiatric disorders: A multi-omic single-nucleus analysis of the human OFC.

ABSTRACT: Psychiatric disorders like schizophrenia, bipolar disorder, and major depressive disorder exhibit substantial genetic and clinical overlap. However, their molecular architecture remains elusive due to their polygenic nature and complex brain cell interactions. We integrated clinical data with genetic susceptibility to investigate gene expression and chromatin accessibility in the orbitofrontal cortex of 92 postmortem human brain samples at the single-nucleus (sn) level. Using snRNA-seq and snATAC-seq, we analyzed ~800,000 and 400,000 nuclei, respectively. We observed cell-type-specific dysregulation related to clinical diagnosis and genetic risk. Dysregulation in gene expression and chromatin accessibility associated with diagnosis was pronounced in excitatory neurons. Conversely, genetic

SUBMITTER: Gerstner N 

PROVIDER: S-EPMC11887846 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature