title: A new method for identifying causal genes of schizophrenia and anti-tuberculosis drug-induced hepatotoxicity.
abstract: Schizophrenia (SCZ) may cause tuberculosis, the treatments for which can induce anti-tuberculosis drug-induced hepatotoxicity (ATDH) and SCZ-like disorders. To date, the causal genes of both SCZ and ATDH are unknown. To identify them, we proposed a new network-based method by integrating network random walk with restart algorithm, gene set enrichment analysis, and hypergeometric test; using this method, we identified 500 common causal genes. For gene validation, we created a regularly updated online database ATDH-SCZgenes and conducted a systematic meta-analysis of the association of each gene with either disease. Till now, only GSTM1 and GSTT1 have been well studied with respect to both diseases; and a total of 23 high-quality association studies were collected for the current meta-analysis validation. Finally, the GSTM1 present genotype was confirmed to be significantly associated with both ATDH [Odds Ratio (OR): 0.71, 95% confidence interval (CI): 0.56-0.90, P = 0.005] and SCZ (OR: 0.78, 95% CI: 0.66-0.92, P = 0.004) according to the random-effect model. Furthermore, these significant results were supported by "moderate" evidence according to the Venice criteria. Our findings indicate that GSTM1 may be a causal gene of both ATDH and SCZ, although further validation pertaining to other genes, such as CYP2E1 or DRD2, is necessary.
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Jiaotong University, Shanghai 200030, China.|Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Tao
authors: T
authors: Huang
authors: School of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
authors: Cheng-Lin
authors: CL
authors: Liu
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Jiaotong University, Shanghai 200030, China.
authors: Lin-Lin
authors: LL
authors: Li
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Jiaotong University, Shanghai 200030, China.
authors: Mei-Hong
authors: MH
authors: Cai
authors: Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors: Wen-Zhong
authors: WZ
authors: Chen
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Jiaotong University, Shanghai 200030, China.|Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors: Yi-Feng
authors: YF
authors: Xu
authors: MRC SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, United Kingdom.
authors: Paul F
authors: PF
authors: O'Reilly
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Jiaotong University, Shanghai 200030, China.|Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors: Lei
authors: L
authors: Cai
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Jiaotong University, Shanghai 200030, China.|Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors: Lin
authors: L
authors: He
mesh_terms: D000465:Algorithms; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1