The genome-wide associated candidate gene ZNF804A and psychosis-proneness: Evidence of sex-modulated association

PLoS One. 2017 Sep 20;12(9):e0185072. doi: 10.1371/journal.pone.0185072. eCollection 2017.

Abstract

Background: The Zinc finger protein 804A (ZNF804A) is a promising candidate gene for schizophrenia and the broader psychosis phenotype that emerged from genome-wide association studies. It is related to neurodevelopment and associated to severe symptoms of schizophrenia and alterations in brain structure, as well as positive schizotypal personality traits in non-clinical samples. Moreover, a female-specific association has been observed between ZNF804A and schizophrenia.

Aim: The present study examined the association of two ZNF804A polymorphisms (rs1344706 and rs7597593) with the positive dimension of schizotypy and psychotic-like experiences in a sample of 808 non-clinical subjects. Additionally, we wanted to explore whether the sexual differences reported in schizophrenia are also present in psychosis-proneness.

Results: Our results showed an association between rs7597593 and both schizotypy and psychotic-like experiences. These associations were driven by females, such those carrying the C allele had higher scores in the positive dimension of both variables compared to TT allele homozygotes.

Conclusion: The findings of the present study support the inclusion of ZNF804 variability in studies of the vulnerability for the development of psychopathology in non-clinical samples and consideration of sex as a moderator of this association.

MeSH terms

  • Adult
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Polymorphism, Single Nucleotide*
  • Psychotic Disorders / genetics*
  • Schizophrenia / genetics
  • Sex Factors

Substances

  • Kruppel-Like Transcription Factors
  • ZNF804A protein, human

Grants and funding

This work was supported by research projects funded by the Spanish Ministry of Economy and Competitiveness (PSI2011-30321-C02-01 and C02-02, PSI2014-54009-R, Red de Excelencia PSI2014-56303-REDT-PROMOSAM: Investigación en Procesos, Mecanismos y Tratamientos Psicológicos para la Promoción de la Salud Mental), Fundació la Marató de TV3 (091110), Comissionat per a Universitats i Recerca of the Generalitat de Catalunya (2014SGR1070 and 2014SGR1636). N. Barrantes-Vidal is funded by the Academia Research Award (ICREA) from the Catalan Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.