Phenome-wide associations with polygenic scores for schizophrenia and major depression in 100,000 Chinese adults
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Phenome-wide association studies of polygenic scores (PGS) can reveal shared genetic influences between mental disorders and other traits. Based on summary statistics in East Asian (EAS) and European (EUR) ancestries, we tested associations of PGS for schizophrenia and major depression with 254 phenotypes in 100,640 Chinese adults. PGS predicted schizophrenia (R 2 =1.96%-3.49%) and major depression (R 2 =0.19%-0.55%) and were associated with various socio-demographic, lifestyle, and physical measures, including poor subjective health and lower household size. The EAS-schizophrenia-PGS was inversely associated with smoking initiation, and the EAS-depression-PGS was inversely associated with BMI. EAS and EUR populations had opposing genetic correlations for smoking-schizophrenia (inverse-EAS, positive-EUR) and BMI-depression (inverse-EAS, positive-EUR). Causality of these relationships was supported by Mendelian Randomisation in EUR, but multivariable analyses suggested pleiotropic effects on other related traits influenced the findings. Our study suggests the context specificity of relationships between mental disorders and other traits, highlighting a potential role of sociocultural factors.
