Background Cirrhosis caused by various factors is the final stage of chronic liver disease. Recent studies have highlighted the critical role of the immune system in its progression, but causality between immunophenotypes and cirrhosis remains unclear. Methods Using a bidirectional two‐sample Mendelian randomization (MR) approach, we analyzed 731 immune cell signatures and cirrhosis risk in East Asian and European populations. Five MR methods were used, with inverse variance weighted (IVW) serving as the primary tool. A meta‐analysis was performed to validate the results in different populations, and sensitivity analyses were conducted to assess the robustness of our findings. Results Forward MR analysis identified three immunophenotypes with protective effects and five with risky effects against cirrhosis in the East Asian population. In the European population, only one type of immune cell was associated with cirrhosis risk but not significantly after FDR adjustment. The meta‐analysis showed a significant association between immune cells and cirrhosis, with genetic diversity and environmental factors influencing the strength of this association in different populations. Reverse MR analysis revealed that no immunophenotype was identified after adjustment. Conclusions Our study reveals the critical role of immune cells in the progression of cirrhosis and identifies potential targets for therapeutic intervention.
Zhang et al. (Thu,) studied this question.