1392-P: Morning Chronotype Reduces the Risk of PCOS—A Mendelian Randomization

Objective: Previous observational studies have suggested a potential connection between PCOS and chronotype, and we aimed to assess the causal relationship between PCOS and chronotype. Methods: A two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and chronotype. The GWAS summary statistics for chronotype were obtained from the UK Biobank, and the GWAS summary statistics for PCOS were obtained from the FinnGen cohort on the IEU Open GWAS Project database. Inverse-variance weighted (IVW) fixed-effect method, the MR-Egger method, and a weighted median method were used for MR estimates. Results: The primary IVW method showed a genetically determined morning chronotype had a significant negative causal relationship with the risk of PCOS. In the main IVW analysis, one unit morning chronotype decreased the incidence of PCOS by 0.86 (OR: 0.14, 95% CI: 0.02 ~ 0.86, P = 0.033). The main IVW estimate was generally consistent with the results of weighted median, weighted mode, and MR-Egger. The MR-PRESSO results showed no outlier SNPs, and the leave-one-out analysis showed that no single SNP has an influence on the overall estimates. Cochran’s Q statistics showed little evidence of heterogeneity between SNPs. There was no evidence of pleiotropy by MR-Egger regression intercept or MR-PRESSO global test (MR-Egger intercept = 0.020, P = 0.835), and symmetry of funnel plots supported the validity of our MR analysis. Conclusion: Our findings indicate that genetically predicted morning chronotype had a significant negative prevalence in PCOS. Disclosure M. Zhang: None. J. Lu: None. D. Dilimulati: None. M. Cai: None. Y. Zhang: None.