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

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