Affiliation:
1. 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 , China
2. Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University , Suzhou , China
3. School of Nursing, Medical College of Soochow University , Suzhou , China
4. Department of Occupational Health, Suzhou Industrial Park Center for Disease Control and Prevention , Suzhou , China
Abstract
Abstract
Background and Hypothesis
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.
Study Design
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.
Results
Eight metabolites were identified associated with psychiatric disorders, including five established mediators: N-acetylornithine (BIP: OR, 0.72 [95% CI, 0.66–0.79]; SCZ: OR, 0.74 [0.64–0.84]), glycine (BIP: OR, 0.62 [0.50–0.77]), docosahexaenoic acid (MDD: OR, 0.96 [0.94–0.97]), 3-Hydroxybutyrate (MDD: OR, 1.14 [1.08–1.21]), butyrylcarnitine (SCZ: OR, 1.22 [1.12–1.32]); and three novel mediators: 1-arachidonoylglycerophosphocholine (1-arachidonoyl-GPC)(BIP: OR, 0.31 [0.23–0.41]), glycoproteins (BIP: OR, 0.94 [0.92–0.97]), sphingomyelins (AN: OR, 1.12 [1.06–1.19]). 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.
Conclusions
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.
Funder
National Natural Science Foundation of China
Natural Science Research Project of Jiangsu Provincial Higher Education
Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions, China
Publisher
Oxford University Press (OUP)
Subject
Psychiatry and Mental health
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