The Effects of Lifestyle Factors on Primary Biliary Cholangitis Ascertained by Two-Sample Mendelian Randomization.

Background: Primary biliary cholangitis (PBC) is a chronic liver disease leading to irreversible cirrhosis and liver failure. This study aims to evaluate the relationships between genetically predicted nine lifestyle factors and PBC by Mendelian randomization (MR).

Methods: Genome-wide association study (GWAS) data were utilized to identify genetic variants significantly associated with specific lifestyle factors, employing a stringent significance threshold of P-value< 5 × 10^-8 and linkage disequilibrium [LD] r² <0.01 with a clumping distance cutoff of 5000 kb. Subsequently, univariable and multivariable MR analyses were conducted, where the inverse variance weighted (IVW) method was considered as the primary analytical approach and then followed by sensitivity analysis.

Results: Non-oily fish intake was causally associated with an increased risk of PBC, with an odds ratio (OR) of 578 (95% confidence interval (CI) 24.17-1.39 × 10⁴). Conversely, the intake of oily fish did not demonstrate a significant decrease in the risk of PBC (P>0.05). There were suggestive associations observed between bread intake and household income (0.00564, P=0.0327).

Conclusion: Our findings underscore the causal relationship between non-oily fish intake and an elevated risk of PBC, as ascertained through both univariable and multivariable MR analyses. These findings hold potential clinical implications for the prevention of PBC.