Causal association between blood immune cells and chronic hepatitis B: Univariable and multivariable Mendelian randomization

Current evidence underscores the pivotal role of the immune system in the pathogenesis of chronic hepatitis B (CHB). Nevertheless, the precise causal nexus between immune cells and CHB remains enigmatic, with numerous unresolved queries. Leveraging data from the latest summary-level genome-wide association studies, we examined immune cell genetics in 3757 individuals from Sardinia. CHB data predominantly originated from the Biobank Japan project, encompassing 1394 cases and 211,059 controls. Our investigation entailed a comprehensive univariable Mendelian randomization (MR) analysis to dissect the potential causal relationship between immune cells and CHB. Initial estimations were conducted employing the inverse-variance weighted method. A battery of tests, including Cochran Q test, leave-one-out test, MR-Egger intercept analysis, and MR-PRESSO test, were employed to evaluate pleiotropy and heterogeneity. Multivariable MR analysis was performed to address potential confounders among immune cells. Overall, our study delineated 10 immune cell types significantly associated with CHB through univariable MR analysis. Among these, 5 immune cell types were implicated as potential contributors to heightened CHB risk, while 5 exhibited protective effects. The robustness of results, potential heterogeneity, and horizontal pleiotropy were examined through sensitivity analysis. Employing multivariable MR, we identified only 2 immune cell types exerting independent effects on CHB, including 2 risk factors. Our findings underscore an intriguing association between select immune cell types and CHB risk, offering potential therapeutic avenues for modulating immune cell function in CHB patients. Nevertheless, this finding warrants further validation through future experimental studies.