Causal Relationship between Chronic Hepatitis B and Stroke in East Asians: A Mendelian Randomization Study

Both chronic hepatitis B (CHB) and stroke contribute to a high burden of disease in the majority of low- and middle-income countries. Epidemiological studies yield conflicting results on the association between CHB and stroke, and the causal relationship remains inconclusive. This study aimed to assess the causal effects of CHB on stroke and its subtypes in East Asians by Mendelian randomization (MR) analysis. Variants associated with CHB were obtained from a genome-wide association study (GWAS) of Chinese samples as instrumental variables. The summary statistics for stroke in East Asians were derived from the largest published GWAS to date. Two-sample MR analyses were implemented to evaluate the causal effects of CHB on stroke and its subtypes by using the canonical inverse variance weighting method and other supplementary approaches. We observed an association between genetic predisposition to CHB and a decreased risk of large-artery atherosclerotic stroke (odds ratio = 0.872, 95% confidence interval = 0.786-0.967, p = 0.010). The causal effects of CHB on other stroke outcomes were not statistically significant. Evidence for heterogeneity and horizontal pleiotropy were not found in our analyses. This study provides genetic evidence for a negative association between CHB and stroke in East Asians, which helps improve our understanding of the etiology of stroke.