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Hot Genes in Schizophrenia: How Clinical Datasets Could Help to Refine their Role

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Abstract

We investigated the effect of a set of SNPs within 5 genes identified by GWASs as possible risk genes for schizophrenia (SCZ) in two independent samples, comprising 176 SCZ patients and 326 controls of Korean origin and 83 SCZ patients and 194 controls of Italian origin. The PANSS was used to assess psychopathology severity and antipsychotic response (AR). Several clinical features were assessed at recruitment. In the Korean sample, the SP4 gene haplotype rs2282888-rs2237304-rs10272006-rs12673091 (p = 0.02) was associated with SCZ. In the Italian sample, PPP3CC rs11780915 (genotypic: p = 0.006; allelic: p = 0.001) and rs2249098 (genotypic: p = 0.0004; allelic: p = 0.00006) were associated with SCZ, as well as the PPP3CC rs11780915-rs10108011-rs2249098 and the ZNF804A rs7603001-rs1344706 haplotypes (p = 0.03 and p = 0.02). Several RORA variants were associated with AR in both the samples, although only the haplotype rs1020729-rs1871858 in the Korean sample survived to the statistical correction (p = 0.01). Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2, and SP4 genes may modulate psychotic symptoms, and (2) RORA and ZNF804A genes may influence AR. Our results partially support a role for these genes in SCZ and AR. Analyses in well phenotyped samples may help to refine the role of the genes identified by GWASs.

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Acknowledgements

The authors thank all the participants in the present study.

Funding

This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0003).

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Authors and Affiliations

  1. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy

    Stefano Porcelli & Alessandro Serretti

  2. Department of Psychiatry, Bucheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, 2 Sosa-Dong, Wonmi-Gu, Bucheon, Kyeonggi-Do, 420-717, Republic of Korea

    Soo-Jung Lee & Chi-Un Pae

  3. Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea

    Changsu Han

  4. Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA

    Ashwin A. Patkar & Chi-Un Pae

  5. Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    Diego Albani

  6. Department of Psychiatry, St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

    Tae-Youn Jun

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  1. Stefano Porcelli
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  2. Soo-Jung Lee
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  3. Changsu Han
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  4. Ashwin A. Patkar
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  5. Diego Albani
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  6. Tae-Youn Jun
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  7. Chi-Un Pae
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  8. Alessandro Serretti
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Corresponding author

Correspondence to Chi-Un Pae.

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The study protocol was approved by the institutional review board (approval number HC10TISI0031). The study protocols were approved by the local Ethical Committees and they have been performed in accordance with the ethical standards laid down in the 1975 Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Porcelli, S., Lee, SJ., Han, C. et al. Hot Genes in Schizophrenia: How Clinical Datasets Could Help to Refine their Role. J Mol Neurosci 64, 273–286 (2018). https://doi.org/10.1007/s12031-017-1016-8

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  • DOI: https://doi.org/10.1007/s12031-017-1016-8

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