Causal associations of multiple obesity indices with preeclampsia: a Mendelian randomization study
10.3760/cma.j.cn113903-20241104-00734
- VernacularTitle:多种肥胖指标与子痫前期的因果关联：一项孟德尔随机化研究
- Author:
Fangcan SUN
1
;
Xiuwu TANG
1
;
Huiyun CHEN
1
;
Xiaoyu LI
1
;
Jinhua ZHOU
1
;
Bing HAN
1
Author Information
1. 苏州大学附属第一医院妇产科，苏州 215006
- Publication Type:Journal Article
- Keywords:
Preeclampsia;
Obesity;
Triglycerides;
Mendelian randomization;
Genome-wide association studies;
Mediation
- From:
Chinese Journal of Perinatal Medicine
2025;28(8):656-662
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the causal relationships between multiple obesity indices, including body mass index (BMI), body fat percentage, whole-body fat mass, trunk fat mass, leg fat percentage, arm fat percentage, waist circumference, and hip circumference, and preeclampsia (PE) using Mendelian randomization (MR), and to evaluate the mediating effect of triglycerides.Methods:Genome-wide association studies (GWAS) summary statistics from European populations were utilized. Independent genetic loci associated with obesity indices and PE served as instrumental variables of exposure and outcomes. Obesity data (approximately 191 000 female samples) came from UK Biobank; PE data ( n=242 852) from FinnGen Biobank. Causal effects were assessed primarily via inverse variance weighted (IVW), supplemented by MR-Egger, weighted median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and Bayesian weighted MR. Bonferroni correction was applied. Cochran's Q test evaluated heterogeneity; MR-Egger intercept test assessed horizontal pleiotropy; leave-one-out, funnel, and scatter plots conducted sensitivity analyses. Odds ratio ( OR) measured effect sizes. Two-step MR explored triglyceride mediation. Results:Eighty-two to 112 single nucleotide polymorphisms were included as instrumental variables. After Bonferroni correction, significant positive causal associations with PE were observed for: BMI (IVW: OR=1.703, 95% CI: 1.469-1.974, P<0.001), body fat percentage (IVW: OR=1.595, 95% CI: 1.321-1.925, P<0.001), whole-body fat mass (IVW: OR=1.639, 95% CI: 1.389-1.934, P<0.001), right leg fat percentage (IVW: OR=1.610, 95% CI: 1.360-1.905, P<0.001), left leg fat percentage (IVW: OR=1.622, 95% CI: 1.363-1.930, P<0.001), right arm fat percentage (IVW: OR=1.591, 95% CI: 1.351-1.872, P<0.001), left arm fat percentage (IVW: OR=1.710, 95% CI: 1.444-2.024, P<0.001), and waist circumference (IVW: OR=1.815, 95% CI: 1.534-2.148, P<0.001). Sensitivity analyses confirmed robustness. Triglycerides mediated 4.6%-8.2% of these effects. Trunk fat mass and hip circumference showed potential positive associations (IVW: OR>1, 0.005≤ P<0.05). Conclusions:Higher BMI, body fat percentage, whole-body fat mass, leg/arm fat percentages, and waist circumference may increase PE risk, with waist circumference showing the strongest association. These effects may be partially mediated by triglycerides.
