Phenome-Wide Associations of Polygenic Scores for Schizophrenia and Major Depression in 100,000 Chinese Adults

China faces significant mental health challenges, with unique associations between mental disorders and other traits observed in its population.

Based on summary statistics of existing genome-wide association studies in East Asian ancestry (EAS) and European ancestry (EUR) populations, we tested the associations of polygenic scores (PGSs) for schizophrenia (SCZ) and major depression (MD) with 254 phenotypes in 100,640 Chinese adults. We also conducted genetic correlation and Mendelian randomization analyses to assess the consistency of these associations across ancestries and infer causality.

The PGSs predicted SCZ (R ² = 2.63%-3.07%) and MD (R ² = 0.21%-0.71%) and were associated with various sociodemographic, lifestyle, and physical factors. Interestingly, based on summary statistics in the EAS population, the schizophrenia PGS was inversely associated with smoking initiation, and the MD PGS was inversely associated with body mass index. Across populations, opposing genetic correlations were observed between smoking initiation and SCZ (inverse in the EAS population, positive in the EUR population) and between body mass index and MD (inverse in the EAS population, positive in the EUR population). Univariable Mendelian randomization supported the causality of these relationships in the EUR population, but multivariable analyses suggested that pleiotropic effects on other related traits (e.g., cannabis use, unhealthy lifestyle) might have influenced the associations.

Our study suggests the context specificity of relationships between mental disorders and other traits, highlighting a potential role of sociocultural factors.