Causal Associations between Pre-pregnancy Obesity Traits and Hypertensive Disorders of Pregnancy: A Two-Sample Mendelian Randomization Analyses.

OBJECTIVE

To investigate potential causal effects of pre-pregnancy obesity traits on hypertensive disorders of pregnancy-gestational hypertension, preeclampsia, and eclampsia-using genetic epidemiology approaches.

METHODS

We performed a comprehensive 2-sample Mendelian randomization (MR) analysis leveraging summary statistics from large-scale genome-wide association studies. Eleven adiposity-related exposure traits were evaluated: BMI, overweight status, obesity (subclassified into grades 1-3), childhood obesity, waist circumference, hip circumference, waist-to-hip ratio, liver fat percentage, visceral adipose tissue volume, and abdominal subcutaneous adipose tissue volume. Primary causal estimates were derived via inverse-variance weighted regression, supplemented by sensitivity analyses using MR-Egger and weighted median methods.

RESULTS

Genetic predisposition to elevated BMI, overweight, obesity, obesity class 1, obesity class 2, childhood obesity, waist-to-hip ratio, and abdominal subcutaneous adipose tissue volume were linked to increased risks of gestational hypertension and preeclampsia. Obesity class 3 also increased the risk of gestational hypertension. Additionally, obesity class 3 and childhood obesity increased the risk of eclampsia. Consistent results were observed using alternative MR methods in sensitivity analyses.

CONCLUSIONS

This genetic evidence substantiates causal effects of multidimensional pre-pregnancy adiposity on hypertensive pregnancy complications. Our findings highlight the importance of life-course weight management strategies beginning in childhood and extending through reproductive planning to mitigate risks of pregnancy-related vascular disorders.