Causal associations of metabolic dysfunction-associated steatotic liver disease with gestational hypertension and preeclampsia: a two-sample Mendelian randomization study

Background: Hypertensive disorders of pregnancy (HDPs), which include gestational hypertension (GH) and preeclampsia (PE), are the primary causes of maternal morbidity and mortality worldwide. Recent studies have found a correlation between metabolic dysfunction-associated steatotic liver disease (MASLD) and HDPs, but the causality of this association remains to be identified. Therefore, this study aims to evaluate the causal relationship between MASLD and HDPs through Mendelian randomization (MR) analysis.

Methods: The summary statistics from genome-wide association studies were employed to conduct a two-sample MR analysis. Five complementary MR methods, including inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode were performed to assess the causality of MASLD on GH and PE. Furthermore, we conducted various sensitivity analyses to ensure the stability and reliability of the results.

Results: Genetically predicted MASLD significantly increased the risk of GH (IVW: OR = 1.138, 95% CI: 1.062-1.220, p < 0.001), while there was little evidence of a causal relationship between MASLD and PE (IVW: OR = 0.980, 95% CI: 0.910-1.056, p = 0.594). The sensitivity analyses indicated no presence of heterogeneity and horizontal pleiotropy.

Conclusion: This MR study provided evidence supporting the causal effect of MASLD on GH. Our findings underscore the significance of providing more intensive prenatal care and early intervention for pregnant women with MASLD to prevent potential adverse obstetric outcomes.