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

Tao Huang1,2, Cheng-Lin Liu3, Lin-Lin Li1

  • 1Bio-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.

Scientific Reports
|September 2, 2016
PubMed

Insights

Researchers identified potential causal genes for schizophrenia and anti-tuberculosis drug-induced liver injury. The GSTM1 gene was significantly associated with both conditions, suggesting a shared genetic link.

Area of Science:

  • Genetics and Genomics
  • Pharmacogenomics
  • Neuroscience

Background:

  • Schizophrenia (SCZ) is linked to tuberculosis, and its treatments can cause anti-tuberculosis drug-induced hepatotoxicity (ATDH) and SCZ-like symptoms.
  • The genetic basis for both SCZ and ATDH remains largely unknown.
  • Identifying shared causal genes could improve treatment strategies and disease understanding.

Purpose of the Study:

  • To identify common causal genes for schizophrenia and anti-tuberculosis drug-induced hepatotoxicity.
  • To validate identified genes through a systematic meta-analysis and an online database.
  • To investigate the role of specific genes, like GSTM1, in the pathogenesis of both diseases.

Main Methods:

  • Development of a novel network-based method integrating random walk, gene set enrichment analysis, and hypergeometric tests.
  • Creation of the ATDH-SCZgenes online database for gene validation.
  • Systematic meta-analysis of 23 high-quality association studies for gene validation.

Main Results:

  • Identification of 500 potential common causal genes using the network-based approach.
  • The GSTM1 present genotype showed significant association with both ATDH (OR: 0.71, P=0.005) and SCZ (OR: 0.78, P=0.004).
  • Findings for GSTM1 were supported by moderate evidence according to Venice criteria.

Conclusions:

  • GSTM1 is a potential causal gene for both anti-tuberculosis drug-induced hepatotoxicity and schizophrenia.
  • Further validation is required for other identified genes, such as CYP2E1 and DRD2.
  • This research provides a foundation for understanding the shared genetic etiology of SCZ and ATDH.

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