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We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate associations of blood lipids with psychiatric disorders.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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\u2009&lt;\u20095\u2009\u00d7\u200910<jats:sup>\u2212\u20098<\/jats:sup>. Summary-level information for the six psychiatric disorders was extracted from Psychiatric Genomics Consortium and Alzheimer Disease Genetics Consortium.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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\u2009=\u20090.91, 95% CI\u2009=\u20090.85\u20130.97, <jats:italic>p<\/jats:italic>\u2009=\u20090.002) and AD (OR\u2009=\u20090.79, 95% CI\u2009=\u20090.71\u20130.88, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and triglycerides (TG) level with the risk of MDD (OR\u2009=\u20091.02, 95% CI\u2009=\u20091.003\u20131.03, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) and panic disorder (OR\u2009=\u20090.83, 95% CI\u2009=\u20090.74\u20130.92, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-023-01692-8","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T14:02:35Z","timestamp":1697637755000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Causal relationships between blood lipids and major psychiatric disorders: Univariable and multivariable mendelian randomization analysis"],"prefix":"10.1186","volume":"16","author":[{"given":"Bozhi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayu","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"issue":"21","key":"1692_CR1","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1001\/jama.291.21.2581","volume":"291","author":"K Demyttenaere","year":"2004","unstructured":"Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine JP, et al. 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