Study of the causal association between homocysteine and preeclampsia through Mendelian randomization

YU Bo; TAN Yahang; HUANG Shiyun

doi:10.3969/j.issn.1004-3594.2026.05.007

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Medical Journal of the Chinese People Armed Police Forces ›› 2026, Vol. 37 ›› Issue (5) : 406-411. DOI: 10.3969/j.issn.1004-3594.2026.05.007

ORIGINAL ARTICLES

Study of the causal association between homocysteine and preeclampsia through Mendelian randomization

YU Bo¹, TAN Yahang², HUANG Shiyun¹

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Abstract

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, supplemented 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 predicted 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 susceptibility and Hcy levels. For each 1 standard deviation increase in genetic risk of preeclampsia, Hcy decreased by approximately 0.52 units (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.

Key words

homocysteine / preeclampsia / Mendelian randomization / causal association / genome-wide association study

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YU Bo, TAN Yahang, HUANG Shiyun. Study of the causal association between homocysteine and preeclampsia through Mendelian randomization[J]. Medical Journal of the Chinese People Armed Police Forces. 2026, 37(5): 406-411 https://doi.org/10.3969/j.issn.1004-3594.2026.05.007

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