Objective: Subthreshold psychosis risk symptoms in the general population may be associated with molecular genetic risk for psychosis. This study sought to optimize the association of risk symptoms with genetic risk for psychosis in a large population-based cohort in the UK (N = 9104 individuals 18–65 years of age) by properly accounting for population stratification, factor structure, and sex.Methods: The newly expanded Generation Scotland: Scottish Family Health Study includes 5391 females and 3713 males with age M [SD] = 45.2  with both risk symptom data and genetic data. Subthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B) and calculation of polygenic risk for schizophrenia was based on 11 425 349 imputed common genetic variants passing quality control. Follow-up examination of other genetic risks included attention-deficit hyperactivity disorder (ADHD), autism, bipolar disorder, major depression, and neuroticism.Results: Empirically derived symptom factor scores reflected interpersonal/negative symptoms and were positively associated with polygenic risk for schizophrenia. This signal was largely sex specific and limited to males. Across both sexes, scores were positively associated with neuroticism and major depressive disorder.Conclusions: A data-driven phenotypic analysis enabled detection of association with genetic risk for schizophrenia in a population-based sample. Multiple polygenic risk signals and important sex differences suggest that genetic data may be useful in improving future phenotypic risk assessment.
Bibliographical noteFunding Information:
This project was supported by the National Institute of Mental Health (grant number K01MH093731 to A.D.); Brain & Behavior Research Foundation Awards (A.D. & A.S.); the Simons Foundation (A.D.); the American Foundation for Suicide Prevention (A.D.); and the Tanner Foundation (A.S.). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the Generation Scotland: Scottish Family Health Study samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award ?Stratifying Resilience and Depression Longitudinally? (STRADL) Reference 104036/Z/14/Z).
© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
- Generation Scotland
PubMed: MeSH publication types
- Journal Article