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Journal of Molecular Neuroscience

, Volume 64, Issue 2, pp 273–286 | Cite as

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

  • Stefano Porcelli
  • Soo-Jung Lee
  • Changsu Han
  • Ashwin A. Patkar
  • Diego Albani
  • Tae-Youn Jun
  • Chi-Un PaeEmail author
  • Alessandro Serretti
Article

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.

Keywords

Schizophrenia Genetic Pharmacogenetics PPP3CC RORA ST8SIA2 SP4 ZNF804A 

Notes

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).

Compliance with Ethical Standards

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.

Conflicts of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12031_2017_1016_MOESM1_ESM.docx (102 kb)
Supplementary Figure 1 (DOCX 102 kb)
12031_2017_1016_MOESM2_ESM.docx (38 kb)
Supplementary Figure 2 (DOCX 38 kb)

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Authors and Affiliations

  1. 1.Department of Biomedical and NeuroMotor SciencesUniversity of BolognaBolognaItaly
  2. 2.Department of Psychiatry, Bucheon St. Mary’s HospitalThe Catholic University of Korea College of MedicineBucheonRepublic of Korea
  3. 3.Department of PsychiatryKorea University, College of MedicineSeoulRepublic of Korea
  4. 4.Department of Psychiatry and Behavioural SciencesDuke University Medical CenterDurhamUSA
  5. 5.Department of NeuroscienceIRCCS - Istituto di Ricerche Farmacologiche Mario NegriMilanItaly
  6. 6.Department of Psychiatry, St. Mary’s HospitalThe Catholic University of KoreaSeoulKorea

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