Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study

Xinzhen Chen; Ting Yao; Jinliang Cai; Xihang Fu; Huiru Li; Jing Wu

doi:10.1016/j.pnpbp.2022.110534

Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jun 8:116:110534. doi: 10.1016/j.pnpbp.2022.110534. Epub 2022 Feb 9.

Authors

Xinzhen Chen¹, Ting Yao¹, Jinliang Cai¹, Xihang Fu¹, Huiru Li¹, Jing Wu²

Affiliations

¹ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
² Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: wujingtj@hust.edu.cn.

PMID: 35150783
DOI: 10.1016/j.pnpbp.2022.110534

Abstract

Systemic inflammation has been thought to play a considerable part in psychiatric disorders. However, the causal relationships between systemic inflammation and psychiatric disorders and the directions of the causal effects remain elusive and need further investigation. By leveraging the summary statistics of genome-wide association studies, the standard inverse variance weighted method was applied to assess the causal associations among 41 systemic inflammatory regulators and 7 major psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia (SCZ), within a two-sample bidirectional Mendelian randomization analysis. Additionally, the weighted median test and the Mendelian randomization pleiotropy residual sum and outlier test were conducted for sensitivity analyses. The results suggested a total of 15 unique systemic inflammatory regulators might be causally associated with disease risk, including 2 for ADHD, 4 for AN, 2 for ASD, 2 for MDD, 2 for OCD, and 5 for SCZ. Among them, the genetically predicted concentration of basic fibroblast growth factor was significantly related to AN at the Bonferroni-corrected threshold (Odds ratio = 0.403, 95% confidence interval = (0.261, 0.622), P = 4.03 × 10^-5). Furthermore, the concentrations of 9 systemic inflammatory regulators might be influenced by neuropsychiatric disorders, including 2 by ADHD, 2 by BIP, 3 by MDD, and 2 by SCZ, and the causal effects of ASD, AN, and OCD need to be further assessed when more significant genetic variants are identified in the future. Overall, this study provides additional insights into the relationships between systemic inflammation and psychiatric disorders and may provide new clues regarding the aetiology, diagnosis and treatment of psychiatric disorders.

Keywords: Cytokines; Inflammation; Mendelian randomization; Psychiatric disorders.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / epidemiology
Attention Deficit Disorder with Hyperactivity* / genetics
Autism Spectrum Disorder* / epidemiology
Autism Spectrum Disorder* / genetics
Genome-Wide Association Study
Humans
Inflammation / genetics
Mendelian Randomization Analysis