Early screening, prevention, and monitoring are vital to reduce preeclampsia risks.

Results may provide new insights for predicting and preventing preeclampsia.

Pregnant women with hypertensive siblings face a higher risk of preeclampsia.

The genetic risk factors for hypertension are also high-risk factors for preeclampsia-eclampsia. This study examined the association of hypertension in family members with preeclampsia-eclampsia in pregnant women through two-sample Mendelian randomization (MR).

Mendelian randomization.

The data for hypertension in siblings, mother, and father were from the UK Biobank, including 364,661, 426,391, and 402,899 individuals, respectively. The data for preeclampsia-eclampsia were FinnGEN R9 (7217 cases and 194,266 controls). Inverse-variance weighted was used as the main analysis method. Weighted median, MR-Egger, simple mode, and weighted mode were complementary MR methods. Heterogeneity was detected using Cochran’s Q-test, horizontal pleiotropy using MR-Egger regression, and driving single-nucleotide polymorphisms (SNPs) using the leave-one-out method.

Mendelian randomization analysis showed that hypertension in family members was positively correlated with preeclampsia-eclampsia risk. The risk of preeclampsia-eclampsia in pregnant women who have siblings with hypertension was the highest (OR = 179.41, 95 % CI: 23.10–1393.65, P = 6.98E-07), followed by hypertension in the mothers (OR = 26.83, 95 % CI: 5.42–132.87, P = 5.56E-05) and the fathers (OR = 18.97, 95 % CI: 1.28–281.29, P = 0.032). The MR-Egger regression test indicated no horizontal pleiotropy (P > 0.05). Cochran’s Q-test showed that the effects of the included SNPs exhibited heterogeneity (P < 0.05). The leave-one-out analysis did not reveal SNPs driving the results by themselves.

The risk of preeclampsia-eclampsia in pregnant women who have siblings with hypertension was the highest, followed by pregnant women with a mother or father with hypertension. Having siblings with hypertension should be considered as a high-risk factor for the early prediction of preeclampsia-eclampsia.

Family members

Hypertension

Preeclampsia-eclampsia

Mendelian randomization

© 2025 The Authors. Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy.