Exploring the Role of Lipid Metabolism Disorders in the Association between Non-Alcoholic Fatty Liver Disease and Depression: A Mendelian Randomization Study
نویسندگان
1 Research Center for Clinical Medicine, Jinshan Hospital Affiliated to Fudan University, Shanghai 20000, China
2 Department of Foreign Languages, University of Chinese Academy of Sciences, Beijing, 101499, China
3 Science & Technology Innovation Center, National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Hunan University of Chinese Medicine, Changsha 410208, China
4 Science & Technology Innovation Center, National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Hunan University of Chinese Medicine, Changsha 410208, China
5 School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
6 School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
doi
10.22034/ircmj.2025.518939.2108چکیده
Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) and depression often co-occur, and both exhibit varying degrees of lipid metabolism disorders. However, the specific role of lipid metabolism disorders in their pathogenesis is unclear. This study aims to use Mendelian randomization (MR) to investigate the causal role of lipid metabolism disorders in the co-morbidity between NAFLD and depression. Methods: A bidirectional MR analysis was conducted using genome-wide association study (GWAS) data. Independent single nucleotide polymorphisms (SNPs) associated with lipid metabolism markers were analyzed to assess their causal effects on NAFLD and depression. Heterogeneity and horizontal pleiotropy were evaluated to ensure result reliability, and a leave-one-out (LOO) analysis was performed to determine the influence of individual SNPs on the outcomes. Results: Bidirectional MR analysis revealed that TG levels (IVW: OR=1.526; 95% CI, 1.300–1.792; P<0.001) were positively associated with NAFLD risk, while HDL levels (IVW: OR=0.807; 95% CI, 0.709–0.920; P=0.001) were negatively associated with it. In the two-sample MR analysis, only elevated TG levels (IVW: OR=1.053; 95% CI, 1.002–1.107; P=0.042) and TC levels (MR-egger: OR=1.307; 95% CI, 1.063–1.606; P=0.025) were significantly associated with an increased risk of depression. Conclusion: High levels of TG act as a direct causal mediator in the co-morbidity between NAFLD and depression, suggesting that regulating TG levels is a new idea for treating their co-morbidities.
