Causal association between serum total bilirubin and cholelithiasis: a bidirectional two-sample Mendelian...

Area of Science:

• Genetics
• Hepatology
• Gastroenterology

Background:

• Observational studies on serum total bilirubin and cholelithiasis have yielded inconsistent results.
• A causal relationship between serum total bilirubin and cholelithiasis requires further investigation.

Purpose of the Study:

• To investigate the causal association between serum total bilirubin and cholelithiasis using a bidirectional two-sample Mendelian randomization (MR) study.
• To determine if serum total bilirubin causally influences cholelithiasis risk and vice versa.

Main Methods:

• Utilized single-nucleotide polymorphisms (SNPs) as instrumental variables in a bidirectional two-sample MR design.
• Employed inverse-variance weighted (IVW) as the primary analysis, supplemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO for robustness and pleiotropy assessment.

Main Results:

• Serum total bilirubin was causally associated with an increased risk of cholelithiasis (beta = 0.10; 95% CI, 0.07 to 0.14; p < 0.001).
• Cholelithiasis was also found to be causally associated with increased serum total bilirubin levels (beta = 0.12; 95% CI, 0.09 to 0.15; p < 0.001).
• Sensitivity analyses confirmed these bidirectional causal associations and indicated minimal influence from potential pleiotropy.

Conclusions:

• Serum total bilirubin has a causal effect on the risk of developing cholelithiasis.
• There is a reciprocal causal relationship, where cholelithiasis also influences serum total bilirubin levels.