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

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.

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.

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.

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.