Causal Association Between Smoking Cessation and Polycystic Ovary Syndrome:A Mendelian Randomization Study

JIN Han; HOU Wenhui

doi:10.3969/j.issn.1004-437X.2026.05.003

Abstract：Objective To investigate the causal relationship between smoking cessation and polycystic ovary syndrome(PCOS).Methods A Mendelian randomization(MR)study was conducted.Single nucleotide polymorphism(SNP)associated with smoking cessation were selected from genome-wide association study(GWAS)data as instrumental variables.Inverse-variance weighted(IVW),MR-Egger regression,and weighted median methods were employed to determine the causal relationship between smoking cessation and PCOS,with odds ratios(OR)and 95％confidence intervals(95％CI)used to evaluate the association strength.Cochran's Q test was applied to assess SNP heterogeneity,while MR-Egger regression tested horizontal pleiotropy.Sensitivity analysis was performed using the leave-one-out method.The MR-pleiotropy residual sum and outlier(MR-PRESSO)test was used to detect outlier SNPs.Results After screening GWAS studies on smoking cessation,seven SNPs were ultimately included in the MR analysis.IVW analysis revealed that smoking cessation reduced the risk of PCOS by 22.7％(OR=0.773,95％CI:0.569-0.944,P=0.016).No significant heterogeneity was observed among SNPs(Cochran's Q=0.864,P=0.990).MR-Egger regression indicated no horizontal pleiotropy(intercept=-0.012,P=0.792).The one-way analysis of variance test showed that no single SNP had a significant impact on the overall results.MR-PRESSO results indicated no statistically significant differences(P=0.059),suggesting no horizontal polygenicity.Conclusion This MR analysis provides evidence that smoking cessation reduces the risk of PCOS development.