Association analysis of preeclampsia and ischemic stroke based on Mendelian randomization study
Objective To explore the causal relationship between preeclampsia and ischemic stroke and its subtypes by using two sample Mendelian randomization method.Methods Summary statistical datasets of preeclampsia,ischemic stroke,and their subtypes was obtained from publicly available genome-wide association studies.The data for preeclampsia was sourced from the FinnGen alliance,including 3 903 cases and 114 753 controls.The data of ischemic stroke and its subtypes comes from the MEGASTROKE alliance,including 34 217 cases of ischemic stroke and 406 111 controls.The subtypes include large artery stroke(4 373 cases and 1463 92 controls),small vessel stroke(5 386 cases and 192 662 controls),and cardiogenic stroke(7 193 cases and 204 570 controls).Inverse variance weighting method,weighted median method,and MR-Egger regression method were used to study the causal relationship between two features,and verify the robustness of the results through sensitivity analysis.Results Seven single nucleotide polymorphism related to preeclampsia were selected as genetic instrumental variables.In the inverse variance weighted method,no evidence was found that preeclampsia was associated with an increased incidence rate of ischemic stroke(OR=1.05,95％CI:0.96-1.15,P=0.3 12).In the analysis of subtypes of ischemic stroke,it was found that gene predicted preeclampsia was associated with increased risk of small vessel stroke(OR=1.21,95％CI:1.05-1.40,P=0.008).No causal relationship was found between preeclampsia and large artery stroke(OR=1.12,95％CI:0.89-1.40,P=0.326)and cardiogenic stroke(OR=1.01,95％CI:0.86-1.20,P=0.857).Sensitivity analysis suggests the absence of horizontal pleiotropy of instrumental variables.The single nucleotide polymorphism,which had a significant impact on the estimated effect value,was not found in the leave-one-out method,indicating once again the stability of the results.Conclusion Genetic prediction of preeclampsia is associated with increased risk of small vessel stroke.Early intervention for individuals with history of preeclampsia is of significant importance in reducing the risk of ischemic stroke
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万方数据
