The genetic overlap between schizophrenia and major depression with cognitive function

This study aimed to systematically dissect the shared genetic basis of schizophrenia (SCZ) and major depression (MD) with cognitive function. To investigate this, we integrated large-scale genome-wide association studies (GWAS) summary statistics for SCZ (N = 175,799, [cases, 74,776; controls, 101,023]), MD (N = 2,622,273 [cases, 550,355; controls, 2,071,918]) and four cognitive traits (reaction time, N = 330,069; memory, N = 112,067; verbal-numerical reasoning, N = 36,035; educational attainment, N = 111,114). Linkage disequilibrium (LD) score regression analysis revealed that SCZ showed significant negative genetic correlations with reaction time, memory, and verbal-numerical reasoning. MD showed negative genetic correlations with memory, verbal-numerical reasoning, and educational attainment. Bayesian colocalization analysis identified seven genomic regions with strong or supportive evidence between SCZ and cognitive function, and two genomic regions with supportive evidence between MD and cognitive function. Gene mapping and over representation analysis (ORA) indicated that SCZ-associated genes were primarily involved in pathways related to transport processes, and MD-associated genes were significantly enriched in pathways related to neural development. Through genetic correlation and colocalization analysis, this study elucidates the genetic overlap between SCZ and MD with cognitive function, providing a new perspective for related research.