Causal relationship between systemic lupus erythematosus and adverse pregnancy outcomes: A two-sample Mendelian randomized study.

ABSTRACT

Background: Systemic lupus erythematosus (SLE) is associated with adverse pregnancy outcome (APO). However, the genetic causality of this association remains unclear. In this study, Mendelian randomization (MR) was used to explore the potential causal relationship between SLE and APO risk. Methods: We selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from published genome-wide association studies (GWAS). APO's statistics are obtained from the GWAS database. MR estimates were performed using the inverse variance-weighted (IVW) method, the MR-Egger method, and the weighted median (WM) method. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept, MR-pleiotropic residual and outlier method, stay-one analysis and funnel plot. Results: The results showed a causal relationship between SLE and pre-eclampsia (OR = 1.036, 95 % confidence interval 1.006 to 1.068, P = 0.019), and no significant causal relationship was found between SLE and other adverse pregnancy outcomes, including postpartum hemorrhage, placental abruption, spontaneous abortion, premature rupture of membranes, fetal distress, gestational diabetes mellitus. These findings were robust in several sensitivity analyses. Conclusion: This MR study demonstrated the causal effect of SLE on preeclampsia. It provides important clues for identifying and early predicting risk factors for preeclampsia.