Wang, Baihan;
Morris, Sam;
Fry, Hannah;
Iona, Andri;
Clarke, Jonathan;
Lin, Kuang;
Pupko, Igor;
... Millwood, Iona Y; + view all
(2025)
Phenome-wide associations of polygenic scores for schizophrenia and major depression in 100,000 Chinese adults.
Biological Psychiatry Global Open Science
, Article 100681. 10.1016/j.bpsgos.2025.100681.
(In press).
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Abstract
Background China faces significant mental health challenges, with unique associations between mental disorders and other traits observed in its population. Methods Based on summary statistics of existing genome-wide association studies in East Asian and European ancestry populations, we tested the associations of polygenic scores for schizophrenia and major depression with 254 phenotypes in 100,640 Chinese adults. We also conducted genetic correlation and Mendelian Randomisation analyses to assess the consistency of these associations across ancestries and infer causality. Results The polygenic scores predicted schizophrenia (R2=2.63%-3.07%) and major depression (R2=0.21%-0.71%), and were associated with various socio-demographic, lifestyle, and physical factors. Interestingly, based on summary statistics in the East Asian ancestry population, the schizophrenia polygenic score was inversely associated with smoking initiation, and the major depression polygenic score was inversely associated with BMI. Across populations, opposing genetic correlations were observed between smoking initiation and schizophrenia (inverse in the East Asian ancestry population; positive in the European ancestry population), and between BMI and major depression (inverse in the East Asian ancestry population; positive in the European ancestry population). Univariable Mendelian Randomisation supported the causality of these relationships in the European ancestry population, but multivariable analyses suggested that pleiotropic effects on other related traits (e.g. cannabis use, unhealthy lifestyle) might have influenced the associations.Conclusions Our study suggests the context specificity of relationships between mental disorders and other traits, highlighting a potential role of sociocultural factors.
| Type: | Article |
|---|---|
| Title: | Phenome-wide associations of polygenic scores for schizophrenia and major depression in 100,000 Chinese adults |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bpsgos.2025.100681 |
| Publisher version: | https://doi.org/10.1016/j.bpsgos.2025.100681 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | polygenic scoreschizophrenia, depression, phenome-wide association study, cross-population comparison, causal inference |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10219734 |
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