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- Title
Identifying causal associations between women's reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis.
- Authors
Sun, Wenxi; Wu, Xiaohui; Yang, Haidong; Yuan, Shiting; Chen, Jun; Fang, Yiru; Zhang, Xiaobin
- Abstract
Background: A significant association between women's reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings. Methods: From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses. Results: The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512–0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407–0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR. Conclusions: Our findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.
- Subjects
GENOME-wide association studies; CONSCIOUSNESS raising; SCHIZOPHRENIA; BODY mass index; SEXUAL intercourse; PATERNAL age effect
- Publication
BMC Psychiatry, 2024, p1
- ISSN
1471-244X
- Publication type
Article
- DOI
10.1186/s12888-024-05614-5