The Mendelian Randomization Study on the Causal Relationship between Systemic Lupus Erythematosus and Pre-eclampsia
Objective:A Mendelian randomization study was used to analyze the causal association between systemic lupus ery-thematosus(SLE)and pre-eclampsia,thus providing a theoretical basis for targeted measures to prevent pre-eclampsia in SLE preg-nancies.Methods:The GWAS database was utilized to screen the study subjects,all of whom were of European ancestry,including 647 cases of SLE and 482 264 controls of European ancestry,and 2 355 cases of pre-eclampsia and 264 887 controls.The analysis was performed using R software,and Mendelian randomization was performed using the inverse variance weighting(IVW)method as well as five validated methods,including the MR-Egger method,the weighted median,the weighted mode,and the simple mode,and sensitivity analyses were performed to test the robustness.Co-localization was used to analyze whether SLE and pre-eclampsia share common genetic causal variants.Results;Mendelian Randomization analysis supported a causal association between Systemic Lupus Erythematosus and an increased risk of Pre-eclampsia[IVW(OR=1.09,95％CI=1.03～1.15,P=0.002)],while reverse MR analysis did not support a causal association between Pre-eclampsia and an increased risk of Systemic Lupus Erythematosus[IVW(OR=1.01,95％CI=0.83～1.23,P=0.899)].In the bidirectional MR analysis,instrumental variables did not exhibit horizontal pleiotropy or heterogeneity,and leave-one-out analysis indicated the robustness and reliability of the results in the two-sample MR analysis.Colocalization analysis did not provide evidence of common genetic causal variants between SLE and Pre-ec-lampsia(H4=2.04％).Conclusion:The results of the Mendelian Randomization method support a causal association between Sys-temic Lupus Erythematosus and an increased risk of Pre-eclampsia.
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