Journal Article

Assessing the Causal Effects of Human Serum Metabolites on 5 Major Psychiatric Disorders

Fan, Yajuan, Ma, Xiancang, Zhao, Binbin, Zheng, Jie, Wang, Wei, Yang, Jian, Bai, Ling, He, Xiaoyan, Yang, Lihong, Ma, Qingyan, Yan, Bin, Zhu, Feng

2020

Overview

Psychiatric disorders are the leading cause of disability worldwide while the pathogenesis remains unclear. Genome-wide association studies (GWASs) have made great achievements in detecting disease-related genetic variants. However, functional information on the underlying biological processes is often lacking. Current reports propose the use of metabolic traits as functional intermediate phenotypes (the so-called genetically determined metabotypes or GDMs) to reveal the biological mechanisms of genetics in human diseases. Here we conducted a two-sample Mendelian randomization analysis that uses GDMs to assess the causal effects of 486 human serum metabolites on 5 major psychiatric disorders, which respectively were schizophrenia (SCZ), major depression (MDD), bipolar disorder (BIP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using genetic variants as proxies, our study has identified 137 metabolites linked to the risk of psychiatric disorders, including 2-methoxyacetaminophen sulfate, which affects SCZ (P = 1.7 × 10–5) and 1-docosahexaenoylglycerophosphocholine, which affects ADHD (P = 5.6 × 10–5). Fourteen significant metabolic pathways involved in the 5 psychiatric disorders assessed were also detected, such as glycine, serine, and threonine metabolism for SCZ (P = .0238), Aminoacyl-tRNA biosynthesis for both MDD (P = .0144) and ADHD (P = .0029). Our study provided novel insights into integrating metabolomics with genomics in order to understand the mechanisms underlying the pathogenesis of human diseases.

• Publisher: Oxford University Press
• Subject: Attention Deficit Disorder with Hyperactivity - blood / Attention Deficit Disorder with Hyperactivity - genetics / Attention Deficit Disorder with Hyperactivity - metabolism / Attention deficit hyperactivity disorder / Autism Spectrum Disorder - blood / Autism Spectrum Disorder - genetics / Autism Spectrum Disorder - metabolism / Bipolar Disorder - blood / Bipolar Disorder - genetics / Bipolar Disorder - metabolism / Depressive Disorder, Major - blood / Depressive Disorder, Major - genetics / Depressive Disorder, Major - metabolism / Genome-Wide Association Study / Germany / Humans / Mendelian Randomization Analysis / Mental disorders / Metabolic Networks and Pathways - genetics / Metabolic Networks and Pathways - physiology / Metabolism / Metabolites / Metabolome - genetics / Metabolome - physiology / Pathogenesis / Regular / Schizophrenia - blood / Schizophrenia - genetics / Schizophrenia - metabolism / United Kingdom