Abdominal obesity mediates the causal relationship between depression and the risk of gallstone disease: retrospective cohort study and Mendelian randomization analyses

Jingxi Li; Jun Zhang; Bingxuan Kong; Li Chen; Jing Yuan; Meian He; Youjie Wang; Sheng Wei; Weihong Chen; Yuhan Tang; Xinhong Zhu; Ping Yao

doi:10.1016/j.jpsychores.2023.111474

Abdominal obesity mediates the causal relationship between depression and the risk of gallstone disease: retrospective cohort study and Mendelian randomization analyses

J Psychosom Res. 2023 Nov:174:111474. doi: 10.1016/j.jpsychores.2023.111474. Epub 2023 Aug 24.

Authors

Jingxi Li¹, Jun Zhang¹, Bingxuan Kong¹, Li Chen¹, Jing Yuan², Meian He², Youjie Wang², Sheng Wei³, Weihong Chen², Yuhan Tang¹, Xinhong Zhu⁴, Ping Yao⁵

Affiliations

¹ Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² Institute of Occupational Medicine and Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁴ School of Nursing, Hubei University of Chinese Medicine, Wuhan 430070, China.
⁵ Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yaoping@mails.tjmu.edu.cn.

PMID: 37689051
DOI: 10.1016/j.jpsychores.2023.111474

Abstract

Objective: Our study aimed to explore the causal effect of depression on the risk of gallstone disease, and the mediation effects of metabolic traits.

Methods: A retrospective cohort study on Chinese elderly from the Dongfeng-Tongji cohort (including 18,141 individuals) was conducted to estimate the adverse effect of probable depression on the risk of gallstone disease. Two-sample Mendelian randomization was performed in European and East-Asian ancestries, to verify the causal relationship between major depression and gallstone disease. We further applied two-step Mendelian randomization to explore the mediation effects of metabolic traits.

Results: In the cohort study, probable depression was associated with an increased risk of gallstone disease within 5 years, with RR (95% CI) of 1.33 (1.12, 1.58) in multivariable regression, and 1.34 (1.11, 1.61) following propensity score weighting. Bidirectional Mendelian randomization in European ancestry revealed a positive causal effect (OR: 1.21; 95% CI: 1.07 to 1.37) of genetically predicted major depression liability on gallstone disease, based on the inverse variance weighted method. Little evidence was presented from other complementary approaches, and the analysis in East-Asian ancestry (IVW estimated OR: 1.03; 95% CI: 0.92 to 1.15). The indirect effect via waist circumference and HDL-C were 1.06 (95% CI: 1.02 to 1.10) and 1.01 (95% CI: 1.00 to 1.01) respectively, which mediated 25.8% and 3.78% of the causal relationship.

Conclusions: Our study suggested a higher risk of gallstone disease in the population with probable depression, while the two-sample Mendelian randomization provided weak evidence for the causal relationship, which was moderately mediated by abdominal obesity.

Keywords: Depression; Gallstone disease; Mediation effects; Mendelian randomization; Metabolic traits.