Sex-specific association between schizophrenia polygenic risk andsubclinical schizophrenia-related traits

Abstract

According to the dimensional view of psychiatric disorders, psychosis is expressed as a continuum inthe general population. However, the investigation of the putative genetic aetiological continuity between itsclinical and subclinical phenotypes has yielded mixed results. We aimed to replicate previous findings regardingthe association of polygenic risk for schizophrenia with subclinical traits (i.e., schizotypy traits and psychotic-likeexperiences), and to examine the role of sex in this association in a large nonclinical sample.Methods: The Multidimensional Schizotypy Scale and the Community Assessment of Psychic Experiences wereassessed in 919 nonclinical participants. Polygenic Risk Scores for schizophrenia (SZ-PRSs) were computed usingthe PRS-CS method based on the latest genome-wide association study of schizophrenia. Summary statisticsderived from the total GWAS sample and stratified by sex were used. Linear regression analyses tested the associationsof the SZ-PRSs with the psychometric variables, both in the total sample and by sex.Results: No associations were found between the SZ-PRSs and the positive, negative or disorganized dimensionsof schizotypy in the total sample. Likewise, no associations were found with psychotic-like experiences. However,the sex-stratified analyses revealed a male-specific association with positive schizotypy. Similar results wereobtained with the PRSs derived from the sex-stratified summary statistics.Discussion: Our results are consistent with the lack of clear evidence of an association between SZ common geneticrisk and its subclinical phenotypes. Nevertheless, the male-specific association found suggests that this PRSmight explain better the male phenotype, as reported in previous studies. Future studies should put a focus on therole of sex in this association to unravel its sex specificities.