Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jul 19, 2022; 12(7): 904-914
Published online Jul 19, 2022. doi: 10.5498/wjp.v12.i7.904
ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population
Xin-Wei Li, Ming-Yuan Zhang, Zhi-Jun Li, Li-Zhe Ai, Meng-Di Jin, Ning-Ning Jia, Meng-Tong Xie, Yu-Qing Yang, Wei-Zhen Li, Lin Dong, Qiong Yu
Xin-Wei Li, Zhi-Jun Li, Li-Zhe Ai, Meng-Di Jin, Ning-Ning Jia, Meng-Tong Xie, Yu-Qing Yang, Wei-Zhen Li, Lin Dong, Qiong Yu, Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
Ming-Yuan Zhang, Department of Endemic Diseases and Parasitic Diseases Prevention, Yantai Center for Disease Control and Prevention, Yantai 264003, Shandong Province, China
Author contributions: Li XW and Zhang MY performed the majority of experiments and wrote the manuscript; Li ZJ and Ai LZ provided advices to the manuscript correction; Jin MD served as scientific advisor and participated in the collection of human material; Jia NN was involved in analytical tools; Xie MT, Yang YQ, Li WZ and Dong L participated in the collection of the human material; Yu Q designed the study and is the guarantor; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81673253; and Jilin Provincial Ministry of Education S&T Project, No. JJKH20190091KJ.
Institutional review board statement: The study was approved by the Ethics Committee of the School of Public Health of Jilin University (No. 2014-03-11).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author Qiong Yu upon reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiong Yu, MD, PhD, Professor, Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No. 1163 Xinmin Street, Chaoyang District, Changchun 130021, Jilin Province, China. yuqiong@jlu.edu.cn
Received: January 28, 2022
Peer-review started: January 28, 2022
First decision: April 18, 2022
Revised: May 2, 2022
Accepted: June 17, 2022
Article in press: June 17, 2022
Published online: July 19, 2022
ARTICLE HIGHLIGHTS
Research background

Schizophrenia (SCZ) is a severe mental disorder bringing heavy burden, which is closely related with genetic and environmental factors. The effect of prenatal exposure of famine on SCZ risk has been reported with intense interest. DNA methylation may be an intermediate factor mediating prenatal famine and SCZ, and DNA methylation quantitative trait locus (meQTLs) can serve as a promising tool.

Research motivation

The lifetime prevalence of SCZ is approximately 1% around the world, and study has reported the highest age-standardized prevalence of SCZ in China. Meanwhile, the Chinese famine of 1959-1961 is a proper source of study subjects to investigate the effect of prenatal famine on SCZ with little available genetic data. As a result, we intended to conduct analyses for SCZ and prenatal famine using native subjects with collected genetic information, which may provide insights specifically for Chinese researchers and patients.

Research objectives

To investigate the associations of four single-nucleotide polymorphisms (SNPs) identified as meQTLs with the risk of SCZ and prenatal famine exposure along with their interactions among Northeast Han Chinese.

Research methods

We recruited 954 Han Chinese from Northeast China including 443 patients with SCZ and 511 healthy controls, and their peripheral blood samples were collected. Among them, 492 born in 1960-1962 were further allocated to a famine group. Four SNPs were selected and genotyped, namely, rs11917047 in PTPRG, rs2239681 in IGF2, rs3842756 in INSIGF, and rs61955196 in ABCB9. The associations of the meQTLs with SCZ risk and prenatal famine, and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction software.

Research results

The genotype distributions along with allele frequencies of the four SNPs were determined among the Chinese participants. We found that rs61955196 was significantly associated with SCZ risk in the log-additive model [odds ratio (OR): 1.22; 95% confidence interval (CI): 1.01-1.48; P = 0.040], and rs61955196 allele was related with an enhanced risk of SCZ (G>C, OR: 1.22; 95%CI: 1.01-1.47; P = 0.042). However, the other three SNPs were not associated with SCZ risk. No association was observed between the SNPs and prenatal famine. Gene-gene interactions were seen between rs2239681 and rs61955196, while no gene-gene or gene-famine interactions were associated with the risk of SCZ.

Research conclusions

Our results suggested that rs61955196 in ABCB9 might be involved in SCZ susceptibility among Northeast Han Chinese.

Research perspectives

Our study provides a potential functional variant rs61955196 for SCZ susceptibility, and we recommend further research to extend the findings to different populations and verify its function. Although no evidence between SCZ and prenatal famine was found, we believe that gathering comprehensive information for analyses regarding subgroups may help to reveal the association in the future.