Chronic hepatitis B infection and pre-eclampsia/eclampsia: a Mendelian randomisation study.

Area of Science:

• Obstetrics and Gynecology
• Infectious Diseases
• Genetics

Background:

• Chronic hepatitis B (CHB) is a significant global health concern.
• The relationship between CHB infection and pre-eclampsia/eclampsia requires further investigation.
• Mendelian randomization (MR) offers a robust approach to explore causal associations.

Purpose of the Study:

• To investigate the potential causal association between CHB infection and the risk of pre-eclampsia/eclampsia.
• To utilize a two-sample MR design leveraging large-scale genome-wide association study (GWAS) data.
• To provide genetic evidence for the link between CHB and hypertensive disorders of pregnancy.

Main Methods:

• Two-sample MR analysis using GWAS summary statistics from UK Biobank and FinnGen datasets.
• Selection of genetic variants strongly associated with CHB infection as instrumental variables (p < 5 × 10⁻⁸).
• Primary analysis using inverse-variance weighted (IVW) method with sensitivity analyses (MR-Egger, weighted median, weighted mode, MR-PRESSO) to ensure robustness.

Main Results:

• MR analysis revealed a significant positive genetic association between CHB infection and an increased risk of pre-eclampsia (OR = 1.154, 95%CI = 1.014-1.313, p = .029).
• A significant positive association was also found for eclampsia (OR = 1.561, 95%CI = 1.030-2.366, p = .035).
• Results remained consistent across various sensitivity analyses, indicating robustness.

Conclusions:

• This study provides compelling genetic evidence that CHB infection causally increases the risk of both pre-eclampsia and eclampsia.
• CHB status should be recognized as a potential risk factor for these pregnancy complications.
• Implementing targeted hepatitis B virus (HBV) screening programs for pregnant women with CHB may improve maternal and fetal outcomes.