Author:
Li Bozhi,Qu Yue,Fan Zhixin,Gong Xiayu,Xu Hanfang,Wu Lili,Yan Can
Abstract
Abstract
Background
Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate associations of blood lipids with psychiatric disorders.
Methods
Univariable and multivariable models were established for MR analyses. Inverse variance-weighted (IVW) MR was employed as the main approach; weighted median and MR-Egger were used as sensitivity analysis methods. The possibility of violating MR assumptions was evaluated utilizing several sensitivity analyses, including heterogeneity statistics, horizontal pleiotropy statistics, single SNP analysis, leave-one-out analysis and MR-PRESSO analysis. As instrumental variables, we screened 362 independent single-nucleotide polymorphisms (SNP) related to blood lipids from a recent genome-wide association study involving 76,627 individuals of European ancestry, with a genome-wide significance level of p < 5 × 10− 8. Summary-level information for the six psychiatric disorders was extracted from Psychiatric Genomics Consortium and Alzheimer Disease Genetics Consortium.
Results
We observed eight significant associations in univariable MR analysis, four of which were corroborated by multivariable MR (MVMR) analysis modified for the other three lipid traits: high-density lipoprotein cholesterol (HDL-C) level with the risk of PTSD (OR = 0.91, 95% CI = 0.85–0.97, p = 0.002) and AD (OR = 0.79, 95% CI = 0.71–0.88, p < 0.001) and triglycerides (TG) level with the risk of MDD (OR = 1.02, 95% CI = 1.003–1.03, p = 0.01) and panic disorder (OR = 0.83, 95% CI = 0.74–0.92, p < 0.001). In addition, four associations were not significant in MVMR analysis after adjustment for three lipid traits: total cholesterol (TC) level with the risk of PTSD, low-density lipoprotein cholesterol (LDL-C) level with the risk of MDD and AD and TG level with the risk of AD.
Conclusions
Our results show that blood lipids and psychiatric disorders may be related in a causal manner. This shows that abnormal blood lipid levels may act as reliable biomarker of psychiatric disorders and as suitable targets for their prevention and treatment.
Funder
National Natural Science Foundation of China
Department of Education of Guangdong Province
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics