Causal association of hypertension in family members with preeclampsia-eclampsia in pregnant women: A two-sample Mendelian randomization study.

OBJECTIVES

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).

STUDY

DESIGN

Mendelian randomization.

MAIN OUTCOME MEASURES: 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.

RESULTS

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.

CONCLUSION

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.