Metabolic abnormalities, liver enzymes increased risk of gallstones: a cross-sectional study and multivariate mendelian randomization analysis

Background and aims: Some studies have explored the relationship between metabolic abnormalities, elevated liver enzymes and gallstone risk, but the results have been inconsistent. The aim of this study was to comprehensively assess the relationship between metabolic abnormalities, liver enzymes, and gallstone risk through a cross-sectional study and Mendelian randomization analysis.

Methods: Firstly, a cross-sectional study was conducted involving 555,31 subjects who underwent physical examinations at the Second Affiliated Hospital of Xi'an Jiaotong University between January 2021 and December 2021. The diagnosis of gallstones was based on ultrasound findings. Multivariable logistic regression analysis was employed to investigate the associations between metabolic abnormalities, liver enzymes, and the risk of gallstones. Additionally, two-sample and multivariate Mendelian randomization analyses were performed to further explore the genetic causal associations.

Results: In the cross-sectional analysis, the detection rate of gallstones was 4.8%, showing a gradual increase with age and BMI (body mass index) in both men and women. Gallstones were found to be comorbid with various metabolic disorders and were associated with elevated liver enzymes. Multivariate analysis showed that female sex, age, body mass index, diastolic blood pressure, fatty liver, alanine aminotransferase, and gamma-glutamyltransferase may be independent risk factors for gallstones, whereas high-density lipoprotein cholesterol may be a protective factor. Two-sample and multivariate Mendelian randomization analyses further revealed a causal association between genetically predicted BMI, type 2 diabetes mellitus, alanine aminotransferase, gamma-glutamyl transferase, and an increased risk of gallstones.

Conclusion: The findings suggest that metabolic abnormalities and elevated liver enzymes may increase the risk of developing gallstones.