Phenome-wide associations of polygenic scores for schizophrenia and major depression in 100,000 Chinese adults

Abstract

China faces significant mental health challenges, with unique associations between mental disorders and other traits observed in its population. Based on summary statistics in East Asian (EAS) and European (EUR) ancestries, we tested associations of polygenic scores (PGS) for schizophrenia and major depression with 254 phenotypes in 100,640 Chinese adults. PGS predicted schizophrenia (R2=1.96%-3.49%) and major depression (R2=0.19%-0.77%), and were associated with various socio-demographic, lifestyle, and physical factors. Interestingly, EAS-schizophrenia-PGS was inversely associated with smoking initiation, and EAS-depression-PGS was inversely associated with BMI. Opposing genetic correlations between ancestries were observed for smoking-schizophrenia (inverse in EAS; positive in EUR) and BMI-depression (inverse in EAS; positive in EUR). Mendelian Randomisation supported the causality of these relationships in EUR, but multivariable analyses suggested the influence of pleiotropic effects on other related traits. Our study suggests the context specificity of relationships between mental disorders and other traits, highlighting a potential role of sociocultural factors.