The Genetic Relationship between Systemic Lupus Erythematosus and Risk of Primary Ovarian Failure: a Two-sample Mendelian Randomization Study

Background: Previous studies investigating the relationship between systemic lupus erythematosus (SLE) and primary ovarian failure (POF) generated conflicting results, especially with the existence of potential environmental confounders. To data, no mendelian randomization study has been applied to examine this causal association between SLE and risk of POF. Methods Genetic instruments for exposure (SLE) were selected from a large GWAS study with 5,201 cases and 9,066 noncases. Outcome data for POF and three reproductive traits (age at menarche, age at menopause, and age at first live birth) were obtained from other eligible GWASs. To estimate causal association, the inverse-variance weighted (IVW) method, MR Egger test, weighted mendelian, simple mode, and weighted mode were applied, with the IVW method to be the primary one. Moreover, sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis, were conducted to ensure the robustness of the results. Results Estimated by the IVW method, SLE was suggested to be causally related to the risk of POF (OR = 1.166, 95% CI: 1.055–1.289, P  = 0.003) and delayed age at first live birth (OR = 1.006, 95% CI: 1.002–1.010, P  = 0.007), with no evidence of a causal association between SLE and age at menopause or menarche. The causal estimates were robust according to sensitivity analysis. Conclusion The two-sample MR study supported a casual association between SLE and POF from a genetic aspect.