Genetic risks of schizophrenia identified in a matched case–control study

Kengo Oishi, Tomihisa Niitsu, Nobuhisa Kanahara, Yasunori Sato, Yoshimi Iwayama, Tomoko Toyota, Tasuku Hashimoto, Tsuyoshi Sasaki, Masayuki Takase, Akihiro Shiina, Takeo Yoshikawa, Masaomi Iyo

Research output: Contribution to journalArticlepeer-review

Abstract

It has been suggested that dopaminergic neurotransmission plays important roles for the psychotic symptoms and probably etiology of schizophrenia. In our recent preliminary study, we demonstrated that the specific allele combinations of dopamine-related functional single nucleotide polymorphisms (SNPs), rs10770141, rs4680, and rs1800497 could indicate risks for schizophrenia. The present validation study involved a total of 2542 individuals who were age- and sex-matched in a propensity score matching analysis, and the results supported the statistical significances of the proposed genetic risks described in our previous reports. The estimated odds ratios were 1.24 (95% CI 1.06–1.45, p < 0.001) for rs4680, 1.73 (95% CI 1.47–2.02, p < 0.0001) for rs1800497, and 1.79 (95% CI 1.35–2.36, p < 0.0001) for rs10770141. A significant relationship was also revealed among these three polymorphisms and schizophrenia, with corresponding coefficients (p < 0.0001). In this study, we also present a new scoring model for the identification of individuals with the disease risks. Using the cut-off value of 2, our model exhibited sensitivity for almost two-thirds of all of the schizophrenia patients: odds ratio 1.87, 95% CI 1.59–2.19, p < 0.0001. In conclusion, we identified significant associations of dopamine-related genetic combinations with schizophrenia. These findings suggest that some types of dopaminergic neurotransmission play important roles for development of schizophrenia, and this type of approach may also be applicable for other multifactorial diseases, providing a potent new risk predictor.

Original languageEnglish
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Case–control study
  • Functional single nucleotide polymorphism
  • Genetic risk
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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