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

BACKGROUND

This study aimed to investigate the potential causal association between chronic hepatitis B (CHB) infection and the risk of pre-eclampsia/eclampsia using a Mendelian randomisation (MR) design.

METHODS

We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from three large-scale datasets. For CHB infection, we used data from 351,885 individuals UK Biobank. For pre‑eclampsia/eclampsia, we analysed two FinnGen datasets with sample sizes of 118,291 and 126,760 individuals, respectively. Genetic variants strongly associated with CHB infection (p < 5 × 10-8) were selected as instrumental variables. The inverse-variance weighted (IVW) method was employed as the primary analysis. Sensitivity analyses included MR-Egger regression, weighted median, weighted mode and MR-PRESSO. Cochran's Q test and MR-Egger intercept tests were performed to assess heterogeneity and horizontal pleiotropy, respectively.

RESULTS

MR analysis revealed significant positive genetic associations between CHB infection and increased risk of pre-eclampsia (OR = 1.154, 95%CI = 1.014-1.313, p = .029) and eclampsia (OR = 1.561, 95%CI = 1.030-2.366, p = .035). Findings were robust across sensitivity analyses for both outcomes.

CONCLUSIONS

Our study provides genetic evidence that CHB infection increases the risk of both pre-eclampsia and eclampsia. These findings suggest that considering CHB status as a risk factor and implementing targeted HBV screening programmes may be beneficial for pregnant women.