TY - JOUR
T1 - Sex-specific association between schizophrenia polygenic risk and subclinical schizophrenia-related traits.
AU - Mas-Bermejo, Patricia
AU - Papiol, Sergi
AU - Torrecilla Gonzalez, Pilar
AU - Lavín Gutiérrez, Valeria
AU - Kwapil, Thomas R.
AU - Barrantes-Vidal, Neus
AU - Rosa, Araceli
N1 - Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2025/1/10
Y1 - 2025/1/10
N2 - Background: According to the dimensional view of psychiatric disorders, psychosis is expressed as a continuum in the general population. However, the investigation of the putative genetic aetiological continuity between its clinical and subclinical phenotypes has yielded mixed results. We aimed to replicate previous findings regarding the association of polygenic risk for schizophrenia with subclinical traits (i.e., schizotypy traits and psychotic-like experiences), 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 were assessed in 919 nonclinical participants. Polygenic Risk Scores for schizophrenia (SZ-PRSs) were computed using the PRS-CS method based on the latest genome-wide association study of schizophrenia. Summary statistics derived from the total GWAS sample and stratified by sex were used. Linear regression analyses tested the associations of 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 dimensions of 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 were obtained 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 genetic risk and its subclinical phenotypes. Nevertheless, the male- specific association found suggests that this PRS might explain better the male phenotype, as reported in previous studies. Future studies should put a focus on the role of sex in this association to unravel its sex specificities
AB - Background: According to the dimensional view of psychiatric disorders, psychosis is expressed as a continuum in the general population. However, the investigation of the putative genetic aetiological continuity between its clinical and subclinical phenotypes has yielded mixed results. We aimed to replicate previous findings regarding the association of polygenic risk for schizophrenia with subclinical traits (i.e., schizotypy traits and psychotic-like experiences), 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 were assessed in 919 nonclinical participants. Polygenic Risk Scores for schizophrenia (SZ-PRSs) were computed using the PRS-CS method based on the latest genome-wide association study of schizophrenia. Summary statistics derived from the total GWAS sample and stratified by sex were used. Linear regression analyses tested the associations of 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 dimensions of 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 were obtained 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 genetic risk and its subclinical phenotypes. Nevertheless, the male- specific association found suggests that this PRS might explain better the male phenotype, as reported in previous studies. Future studies should put a focus on the role of sex in this association to unravel its sex specificities
KW - Genetic overlap
KW - Polygenic risk score
KW - Psychotic-like experiences
KW - Schizophrenia
KW - Schizotypy
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85205832821&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e5edf780-50d5-3ba4-8860-376792829fe5/
U2 - 10.1016/j.pnpbp.2024.111161
DO - 10.1016/j.pnpbp.2024.111161
M3 - Article
C2 - 39368539
VL - 136
JO - Progress in Neuropsychopharmacology & Biological Psychiatry
JF - Progress in Neuropsychopharmacology & Biological Psychiatry
M1 - 111161
ER -