Xin Qi1, Fanglin Guan2, Yan Wen1, Ping Li1, Mei Ma1, Shiqiang Cheng1, Lu Zhang1, Chujun Liang1, Bolun Cheng1, Feng Zhang3. 1. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China. 2. School of Medicine & Forensics, Xi'an Jiaotong University, Xi'an, PR China. 3. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China. Electronic address: fzhxjtu@mail.xjtu.edu.cn.
Abstract
BACKGROUND: Schizophrenia (SCZ) is a severe mental disorder. Both environmental and genetic factors contribute to the development of SCZ. The estimated heritability of SCZ is about 80%. Previous genetic studies of SCZ mainly focused on the genetic variations associated the risk of SCZ. Limited efforts are paid to explore the roles and biological mechanism of nuclear acid methylation implicated in the pathogenesis of SCZ. METHODS: A two-stage integrative analysis of SCZ GWAS and nuclear acid methylation functional annotation data (including meQTLs and m6A) was performed in this study. First, the discovery GWAS of SCZ was aligned with genomic meQTLs and m6A annotation data to identify the candidate genes associated with SCZ. Second, another independent replication GWAS dataset of SCZ was applied to validate the discovery results. Furthermore, the functional relevance of identified candidate genes with SCZ were validated by the mRNA expression profiling of SCZ brain tissues. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes was performed by the DAVID tool. RESULTS: The two-stage integrative analysis detected 106 meQTLs related candidate genes for SCZ. After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1. Besides, for meQTLs, 29 SCZ associated pathways and 56 SCZ associated GO terms were detected, such as cell adhesion molecules and asthma. For m6A, 25 candidate genes were detected by the two-stage integrative analysis for SCZ, such as ZSCAN12, HLA-DQA1 and SNX19. Furthermore, 17 of the 25 genes were detected in the mRNA expression profiling of SCZ brain tissues. CONCLUSION: This study identified multiple SCZ associated genes and pathways, supporting the implication of nuclear acid methylation in the pathogenesis of SCZ.
BACKGROUND:Schizophrenia (SCZ) is a severe mental disorder. Both environmental and genetic factors contribute to the development of SCZ. The estimated heritability of SCZ is about 80%. Previous genetic studies of SCZ mainly focused on the genetic variations associated the risk of SCZ. Limited efforts are paid to explore the roles and biological mechanism of nuclear acid methylation implicated in the pathogenesis of SCZ. METHODS: A two-stage integrative analysis of SCZ GWAS and nuclear acid methylation functional annotation data (including meQTLs and m6A) was performed in this study. First, the discovery GWAS of SCZ was aligned with genomic meQTLs and m6A annotation data to identify the candidate genes associated with SCZ. Second, another independent replication GWAS dataset of SCZ was applied to validate the discovery results. Furthermore, the functional relevance of identified candidate genes with SCZ were validated by the mRNA expression profiling of SCZ brain tissues. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes was performed by the DAVID tool. RESULTS: The two-stage integrative analysis detected 106 meQTLs related candidate genes for SCZ. After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1. Besides, for meQTLs, 29 SCZ associated pathways and 56 SCZ associated GO terms were detected, such as cell adhesion molecules and asthma. For m6A, 25 candidate genes were detected by the two-stage integrative analysis for SCZ, such as ZSCAN12, HLA-DQA1 and SNX19. Furthermore, 17 of the 25 genes were detected in the mRNA expression profiling of SCZ brain tissues. CONCLUSION: This study identified multiple SCZ associated genes and pathways, supporting the implication of nuclear acid methylation in the pathogenesis of SCZ.
Authors: Xueming Yao; Joseph T Glessner; Junyi Li; Xiaohui Qi; Xiaoyuan Hou; Chonggui Zhu; Xiaoge Li; Michael E March; Liu Yang; Frank D Mentch; Heather S Hain; Xinyi Meng; Qianghua Xia; Hakon Hakonarson; Jin Li Journal: Transl Psychiatry Date: 2021-01-21 Impact factor: 6.222
Authors: Amra Saric; Spencer A Freeman; Chad D Williamson; Michal Jarnik; Carlos M Guardia; Michael S Fernandopulle; David C Gershlick; Juan S Bonifacino Journal: Nat Commun Date: 2021-07-27 Impact factor: 14.919