Investigating the genetic architecture of general and specific psychopathology in adolescence
Open accessAbstract
Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age. PRSs for schizophrenia, major depressive disorder, neuroticism and bipolar disorder were generated for individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariate linear regression was used to examine the relationships of these PRSs with psychopathology factors modelled within (i) a correlated factors structure and (ii) a bifactor structure. The schizophrenia PRS was associated with an increase in factors describing psychotic experiences, negative dimension, depression and anxiety, but, when modelling a general psychopathology factor based on these measures, specific effects above this persisted only for the negative dimension. Similar factor relationships were observed for the neuroticism PRS, with a (weak) specific effect only for anxiety once modelling general psychopathology. Psychopathology during adolescence can be described by a general psychopathology construct that captures common variance as well as by specific constructs capturing remaining non-shared variance. Schizophrenia risk genetic variants identified through genome-wide association studies mainly index negative rather than positive symptom psychopathology during adolescence. This has potentially important implications both for research and risk prediction in high-risk samples.
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A common framework is comparisons between bifactor and correlated factor models using confirmatory factor analysis.
“A common framework is comparisons between bifactor (Figure 2A) and correlated factor models (Figure 2B) using confirmatory factor analysis (27,28,32–35,37–39).”
From Methods and challenges for assessing heterogeneity (2020) · cites this paper as [38]
Schizophrenia and neuroticism polygenic risk scores were more associated with the p factor than specific factors such as anxiety.
“From 3650 children’s genetic and clinical data within the Avon Longitudinal Study of Parents and Children cohort, investigators found that schizophrenia and neuroticism polygenic risk scores were more associated with p factor than specific factors such as anxiety (38).”
From Methods and challenges for assessing heterogeneity (2020) · cites this paper as [38]
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- Authors
- Jones, H. J., Heron, J., Hammerton, G., Stochl, J., Jones, P. B., Cannon, M., Smith, G. D., Holmans, P., Lewis, G., Linden, D. E. J., O’Donovan, M. C., Owen, M. J., Walters, J., Zammit, S., & the 23 and Me Research Team
- Affiliations
- University Hospitals Bristol NHS Foundation Trust (GB)
- University of Bristol (GB)
- University of Cambridge (GB)
- Royal College of Surgeons in Ireland (IE)
- Cardiff University (GB)
- University College London (GB)
- Corresponding author
- Jones, Hannah J.
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2018-08-08
- Volume
- 8
- Issue
- 1
- Pages
- 145-145
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6082910
- OpenAlex
- W2887115072
- Cited by
- 59
- References
- 64
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 10
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Funders
- Medical Research Council (G0701503, MR/M006727/1 and MR/K004360/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- polygenic risk score, schizophrenia, adolescent psychopathology, general psychopathology, internalizing disorders, psychotic experiences, negative symptoms, neuroticism, major depressive disorder, bipolar disorder, bifactor model, Avon Longitudinal Study of Parents and Children, developmental pathways, risk prediction
- MeSH terms
- Neuroticism, Adolescent, Bipolar Disorder, Major Depressive Disorder, Female, Humans, Longitudinal Studies, Male, Psychopathology, Risk Factors, Schizophrenia, Schizophrenic Psychology, Genetic Variation, Multivariate Analysis, Linear Models, Risk Assessment, Genetic Predisposition to Disease, Genome-Wide Association Study, Self Report
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