Bidirectional Mendelian randomization analysis of plasma lipidome and psychiatric disorders

作者：Ling Yu, Qing Long, Yunqiao Zhang, Yilin Liu, Ziwei Guo, Xiang Cao, Fuyi Qin, Yangyang Xu, Qingqing Qian, Biyao Gao, Jian Chen, Jie Liu, Yong Zeng, Zhaowei Teng · 发表于：Journal of Affective Disorders · 年份：2024 · DOI：10.1016/j.jad.2024.10.063 · 被引用次数：5 · 研究领域：Genetic Associations and Epidemiology、Metabolomics and Mass Spectrometry Studies、Adipokines, Inflammation, and Metabolic Diseases

BACKGROUND: Evidence from observational studies and clinical experiments suggests a close association between plasma lipidome and psychiatric disorders. However, the causal relationship between plasma lipidome and psychiatric disorders remains insufficiently determined. Plasma lipidome are relatively easy to measure and regulate clinically, and they play a crucial role in neuronal signal transduction, making them a focus of interest as potential therapeutic targets for psychiatric disorders. METHODS: In this study, we utilized the latest Finnish population-based genome-wide association study (GWAS) data on 179 lipid species. We downloaded data on five psychiatric disorders from the IEU database, including schizophrenia, bipolar disorder, depression, autism from the PGC consortium, and anxiety disorder from the Neale lab. Using two-sample bidirectional Mendelian randomization (MR) analysis, we assessed the relationship between these 179 lipid species and the risk of the five psychiatric disorders. To validate the assumptions of Mendelian randomization, we conducted tests for horizontal pleiotropy and heterogeneity. RESULTS: After applying FDR correction to assess the relationship between 179 lipid species traits and the risk of five psychiatric disorders, our analysis provided evidence of a causal relationship specifically between genetic susceptibility in the plasma lipidome and bipolar disorder. This relationship notably involves eight phosphatidylcholines (PCs) and two ster...