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Association Between Human Blood Metabolome and the Risk of Psychiatric Disorders

代谢组 重性抑郁障碍 精神科 孟德尔随机化 双相情感障碍 医学 精神分裂症(面向对象编程) 代谢物 内科学 生物 遗传学 心情 遗传变异 基因型 基因
作者
Yiming Jia,Hui Li,Lulu Sun,Daoxia Guo,Mengyao Shi,Kaixin Zhang,Pinni Yang,Yu Wang,Fanghua Liu,Ouxi Shen,Zhengbao Zhu
出处
期刊:Schizophrenia Bulletin [Oxford University Press]
卷期号:49 (2): 428-443 被引量:2
标识
DOI:10.1093/schbul/sbac130
摘要

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.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.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.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.
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