1. Causal association between mitochondrial function and psychiatric disorders: Insights from a bidirectional two-sample Mendelian randomization study.
- Author
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Lin YL, Yao T, Wang YW, Lu JH, Chen YM, Wu YQ, Qian XG, Liu JC, Fang LX, Zheng C, Wu CH, and Lin JF
- Subjects
- Humans, Causality, Genetic Predisposition to Disease, Autism Spectrum Disorder genetics, White People genetics, Polymorphism, Single Nucleotide, Mitochondrial Proteins genetics, Mendelian Randomization Analysis, Genome-Wide Association Study, Mental Disorders genetics, Mitochondria genetics, Alzheimer Disease genetics
- Abstract
Background: Previous observational studies have suggested that there appears to be a close association between mitochondrial function and psychiatric disorders, but whether a causal role exists remains unclear., Methods: We extracted genetic instruments for 67 mitochondrial-related proteins and 10 psychiatric disorders from publicly available genome-wide association studies, and employed five distinct MR methods and false discovery rate correction to detect causal associations between them. Additionally, we conducted a series of sensitivity tests and additional model analysis to ensure the robustness of the results. For potential causal associations, we further performed reverse MR analyses to assess the impact of reverse causality., Results: We identified a total of 2 significant causal associations and 24 suggestive causal associations. Specifically, Phenylalanine-tRNA ligase was found to increase the risk of Alzheimer's disease, while Mitochondrial glutamate carrier 2 decreased the risk of autism spectrum disorder. Furthermore, there was no evidence of significant pleiotropy, heterogeneity, or reverse causality., Limitations: This study was limited to individuals of European ancestry, and the conclusions drawn are merely revelatory., Conclusion: This study provides novel insights into the relationship between mitochondria and psychiatric disorders, as well as the pathogenesis and treatment strategies for psychiatric disorders., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2025
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