同型半胱氨酸与子痫前期的因果关联:孟德尔随机化研究OA

Objective To evaluate the causal association between homocysteine(Hcy)and preeclampsia through two-sample Mendelian randomization(MR).Methods Based on the data from genome-wide association studies(GWAS),a forward analysis was conducted with Hcy as the exposure and preeclampsia as the outcome.Genetic variants significantly associated with Hcy(SNPs)were selected as instrumental variables,and the inverse variance weighted method(IVW)was used as the main analysis method,supple-mented by MR-Egger regression for sensitivity analysis.Heterogeneity and horizontal pleiotropy were assessed using Cochran's Q test and the MR-Egger intercept tests respectively,and the leave-one-out analysis was performed to examine the influence of individual SNPs.In the reverse-direction analysis,preeclampsia was treated as the exposure and Hcy as the outcome.Results Genetically pre-dicted higher Hcy levels were causally associated with an increased risk of preeclampsia.Each 1-unit increase in Hcy was associated with significantly higher risk of preeclampsia(OR=3.92,P=2.97×10-6),with no significant heterogeneity or horizontal pleiotropy,supporting the robustness of the findings.The reverse-direction analysis showed a negative association between preeclampsia suscepti-bility and Hcy levels.For each 1 standard deviation increase in genetic risk of preeclampsia,Hcy decreased by approximately 0.52 u-nits(β=-0.519,SE=0.103,P=4.75×10-7).Conclusions Based on genetic data,the overall evidence supports a positive causal association between homocysteine and preeclampsia,suggesting a potential etiological role for Hcy.