Bridging Three Years of Insights: Examining the Association Between Depression and Gallstone Disease

Abstract

Background: Despite sharing common pathophysiological risk factors, the relationship between gallstones and depression requires further evidence for a clearer understanding. This study combines the National Health and Nutrition Examination Survey 2017 - 2020 observational data and Mendelian randomization (MR) analysis to shed light on the potential correlation between these conditions.

Methods: By analyzing the National Health and Nutrition Examination Survey 2017 - 2020 data through weighted multivariable-adjusted logistic regression, we examined the association between depression and gallstone risk. MR was subsequently applied, utilizing genetic instruments from a large genome-wide association study on depression (excluding 23andMe, 500,199 participants) and gallstone data (28,627 cases, 348,373 controls), employing the main inverse variance-weighted method alongside other MR methods to explore the causal relationship. Sensitivity analyses validated the study's conclusions.

Results: Among the 5,303 National Health and Nutrition Examination Survey participants, a significant association was found between depressive symptoms and increased gallstone risk (initial odds ratio (OR) = 2.001; 95% confidence interval (CI) = 1.523 - 2.598; P < 0.001), with the association persisting after comprehensive adjustments (final OR = 1.687; 95% CI = 1.261 - 2.234; P < 0.001). MR findings also indicated a causal link between genetically predicted depression and higher gallstone risk (OR = 1.164; 95% CI = 1.053 - 1.286; P = 0.003).

Conclusions: Depression is significantly associated with a higher risk of gallstones, supported by genetic evidence suggesting a causal link. These findings highlight the importance of considering depression in gallstone risk assessments and management strategies.

Keywords: Causality; Depression; Gallstone; Mendelian randomization analysis; National Health and Nutrition Examination Survey.

Figure 1

Flowchart on the stages of sample selection in this study. PHQ-9: Patient Health Questionnaire-9.

Figure 2

Independent effect of depression on the risk of gallstone disease using multivariable Mendelian randomization analysis. Model 1: independent effect of depression on gallstone disease after adjusting for cigarettes per day. Model 2: independent effect of depression on gallstone disease after adjusting for drinking. Model 3: independent effect of depression on gallstone disease after adjusting for education attainment (EA). Cigday: Heaviness of smoking was measured with cigarettes per day; OR: odds ratio; CI: confidence interval.

Figure 3

Results from the leave-one-out analysis which excluded each single nucleotide polymorphism to estimate the effects of depression-related traits on gallstone disease.