{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:00:24Z","timestamp":1791237624277,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T00:00:00Z","timestamp":1663459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103917"],"award-info":[{"award-number":["82103917"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103921"],"award-info":[{"award-number":["82103921"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Research Project of Jiangsu Provincial Higher Education","award":["21KJB330006"],"award-info":[{"award-number":["21KJB330006"]}]},{"name":"Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions, China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Hypothesis<\/jats:title><jats:p>To identify promising drug targets for psychiatric disorders, we applied Mendelian randomization (MR) design to systematically screen blood metabolome for potential mediators of psychiatric disorders and further predict target-mediated side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>We selected 92 unique blood metabolites from 3 metabolome genome-wide association studies (GWASs) with totally 147 827 participants. Summary statistics for bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), schizophrenia (SCZ), panic disorder (PD), autistic spectrum disorder (ASD), and anorexia nervosa (AN) originated from the Psychiatric Genomics Consortium, involving 1 143 340 participants. Mendelian randomization (MR) analyses were conducted to estimate associations of blood metabolites with psychiatric disorders. Phenome-wide MR analysis was further performed to predict side effects mediated by metabolite-targeted interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight metabolites were identified associated with psychiatric disorders, including five established mediators: N-acetylornithine (BIP: OR, 0.72 [95% CI, 0.66\u20130.79]; SCZ: OR, 0.74 [0.64\u20130.84]), glycine (BIP: OR, 0.62 [0.50\u20130.77]), docosahexaenoic acid (MDD: OR, 0.96 [0.94\u20130.97]), 3-Hydroxybutyrate (MDD: OR, 1.14 [1.08\u20131.21]), butyrylcarnitine (SCZ: OR, 1.22 [1.12\u20131.32]); and three novel mediators: 1-arachidonoylglycerophosphocholine (1-arachidonoyl-GPC)(BIP: OR, 0.31 [0.23\u20130.41]), glycoproteins (BIP: OR, 0.94 [0.92\u20130.97]), sphingomyelins (AN: OR, 1.12 [1.06\u20131.19]). Phenome-wide MR analysis showed that all identified metabolites except for N-acetylornithine and 3-Hydroxybutyrate had additional effects on nonpsychiatric diseases, while glycine, 3-Hydroxybutyrate, N-acetylornithine, and butyrylcarnitine had no adverse side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This MR study identified five established and three novel mediators for psychiatric disorders. N-acetylornithine, glycine, 3-Hydroxybutyrate, and butyrylcarnitine might be promising targets against psychiatric disorders with no predicted adverse side effects.<\/jats:p><\/jats:sec>","DOI":"10.1093\/schbul\/sbac130","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T09:06:18Z","timestamp":1663664778000},"page":"428-443","source":"Crossref","is-referenced-by-count":42,"title":["Association Between Human Blood Metabolome and the Risk of Psychiatric Disorders"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-7879","authenticated-orcid":false,"given":"Yiming","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University , Suzhou , 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