Causal association between dietary factors and Primary Biliary Cholangitis: A Mendelian randomization study.

The potential relationship between dietary intake and primary biliary cholangitis (PBC) remains uncertain. This study employed a 2-sample Mendelian randomization (MR) approach to investigate the causal link between dietary habits and PBC development, while also assessing potential mediating roles of PBC risk factors. We performed a 2-sample MR analysis using publicly accessible genome-wide association study data. Various MR methods including inverse-variance weighted, MR-Egger, weighted median, and others were utilized. Sensitivity analyses were conducted to ensure robustness of the findings. Following multiple testing adjustment, 2 dietary factors showed significant causal relationships with PBC. Cereal consumption was inversely associated with PBC risk (OR = 0.006, 95% CI: 0-0.089, P = .000198, Bonferroni-adjusted P = .007), whereas nonoily fish intake was positively associated (OR = 578.684, 95% CI: 24.173-13853.312, P = 8.64 × 10-05; Bonferroni-adjusted P = .003). Several other associations were nominally significant (unadjusted P < .05), including weekly beer and cider intake (Neale Lab: OR = 0.038, 95% CI: 0.002-0.597, P = .020; MRC-IEU: OR = 0.059, 95% CI: 0.006-0.549, P = .013), bread intake (OR = 61.404, 95% CI: 1.558-2419.859, P = .028), salad/raw vegetable intake (OR = 0.012, 95% CI: 0-0.714, P = .034), and tea intake (OR = 0.169, 95% CI: 0.037-0.767, P = .021). Notably, the effect estimates for bread and nonoily fish intake were highly imprecise, as indicated by extremely wide confidence intervals. Sensitivity analyses supported the robustness of the primary inverse-variance weighted estimates. No evidence of causal effects was found for the other dietary exposures examined. This MR study provides genetic evidence that a predisposition toward higher cereal intake may lower the risk of PBC, while a genetic tendency for nonoily fish consumption may markedly increase risk. The nominal associations observed for beer/cider, bread, salad/raw vegetables, and tea merit further investigation in larger cohorts. The implausible effect sizes for certain exposures call for cautious interpretation and additional validation.