Depression increases the risk of gallstone: A cross-sectional study and Mendelian randomization analysis.

ABSTRACT

BACKGROUND: Gallstone, a common digestive disorder, poses a significant public health burden. Concurrently, depression is acknowledged as a health risk. However, limited information exists on depression's impact on gallstone formation. This study investigates depression's causal effect on gallstone risk. METHODS: Using National Health and Nutrition Examination Survey (NHANES) data, we conducted an observational study. The severity of depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression and subgroup analyses explored the correlation between depression and gallstone risk. Mendelian Randomization (MR) analysis, leveraging Genome-Wide Association Studies (GWAS) data, reduced observational bias and elucidated causality. Inverse Variance Weighting (IVW) was the primary method, with sensitivity analyses validating results. RESULTS: In the observational study (7707 participants), gallstone risk was elevated in mild (OR 1.58, 95 % CI 1.31-1.90, P < 0.001), moderate (OR 2.07, 95 % CI 1.59-2.67, P < 0.001), and severe (OR 2.41, 95 % CI 1.70-3.34, P < 0.001) depression groups (P for trend <0.001). Subgroup analyses revealed a stronger association in those under 65, females, non-Hispanic Black, individuals with obesity, smokers, and those with college education or higher. Mendelian Randomization indicated a causal link between genetically predicted depression and higher cholelithiasis risk (OR 2.06, 95 % CI 1.34-3.17, P = 0.001), validated through sensitivity analyses and multi-cohort verification. CONCLUSION: Depression independently increases gallstone risk, particularly in those under 65, females, non-Hispanic Black, individuals with obesity, smokers, and those with college education or higher. Further validation is needed through multi-center, prospective cohort studies.