A new method for identifying causal genes of schizophrenia and anti-tuberculosis drug-induced hepatotoxicity

Tao Huang, Cheng Lin Liu, Lin Lin Li, Mei Hong Cai, Wen Zhong Chen, Yi Feng Xu, Paul O'Reilly, Lei Cai*, Lin He

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
155 Downloads (Pure)

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.

Original languageEnglish
Article number32571
JournalScientific Reports
Volume6
Early online date1 Sept 2016
DOIs
Publication statusE-pub ahead of print - 1 Sept 2016

Fingerprint

Dive into the research topics of 'A new method for identifying causal genes of schizophrenia and anti-tuberculosis drug-induced hepatotoxicity'. Together they form a unique fingerprint.

Cite this