Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: A novel strategy for complex disorders

Q. Xu, Y. B. Jia, B. Y. Zhang, K. Zou, Y. B. Tao, Y. P. Wang, B. Q. Qiang, G. Y. Wu, Y. Shen, H. K. Ji, Y. Huang, X. Q. Sun, L. Ji, Y. D. Li, Y. B. Yuan, L. Shu, X. Yu, Y. C. Shen, Y. Q. Yu, G. Z. JuShu Zheng Liu, Jie Ping Shi

Research output: Contribution to journalArticlepeer-review

Abstract

Schizophrenia is a common mental disorder with a complex pattern of inheritance. Despite a large number of studies in the past decades, its molecular etiology remains unknown. In this study, we proposed a 'system-thinking' strategy in seeking the combined effect of susceptibility genes for a complex disorder by using paranoid schizophrenia as an example. We genotyped 85 reported single-nucleotide polymorphisms (SNPs) present in 23 genes for the dopamine (DA) metabolism pathway among 83 paranoid schizophrenics and 108 normal controls with detailed clinical and genetic information. We developed two novel multilocus approaches - the potential effective SNP combination pattern and potential effective dynamic effects analysis, by which three susceptibility genotype combinations were found to be associated with schizophrenia. These results were also validated in a family-based cohort consisting of 95 family trios of paranoid schizophrenia. The present findings suggest that the COMT and ALDH3 combination may be the most common type involved in predisposing to schizophrenia. Since the combination blocks the whole pathways for the breakdown of DA and noradrenaline, it is very likely to play a central role in developing paranoid schizophrenia.

Original languageEnglish (US)
Pages (from-to)510-521
Number of pages12
JournalMolecular psychiatry
Volume9
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Clinial subgroup
  • Complex disorder
  • Dopamine metabolic pathway
  • Effective SNP combination pattern
  • Potential effective dynamic effects
  • Schizophrenia
  • Single nucleotide polymophism
  • Susceptibility genotype combinations

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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