Causal effects of gestational hypertension on women's health: A Mendelian randomization analysis

Gestational hypertension (GH) is linked to complications impacting women's health, with confounded causal links in observational studies. This study used Mendelian randomization (MR) to investigate GH's effects on women's diseases.

To reduce confounding and identify robust GH associations, we selected 149 single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). The data were extracted from publicly accessible genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method served as the primary MR analysis, with sensitivity verification conducted through MR-Egger, weighted median, weighted mode, and simple mode analyses.

MR analysis found no significant causal links between GH and postpartum conditions, such as mental and behavioral disorders, postpartum hemorrhage, puerperal sepsis, or depression. However, GH significantly increased stroke risk in women (P_IVW = 0.0103, odds ratio [OR]: 1.009, 95% confidence interval [CI:] 1.002-1.016). No causal relationships were detected between GH and Alzheimer's, severe depression, Parkinson's, diabetes, gestational diabetes, polycystic ovary syndrome (PCOS), or cancers, including ovarian, bowel, cervical, endometrial, breast, and lung cancer. Sensitivity analyses showed no pleiotropic effects.

GH is causatively linked to higher stroke risk in women, underscoring the need for focused monitoring and interventions to mitigate long-term health risks in this group.