Predicting Cognitive Executive Functioning with Polygenic Risk Scores for Psychiatric Disorders
Open accessAbstract
Executive functions (EFs) have been proposed as an endophenotype for psychopathology because EF deficits are associated with most psychiatric disorders. To examine this hypothesis, we derived polygenic risk scores for autism, attention-deficit/hyperactive disorder (ADHD), bipolar disorder, major depression (MDD), and schizophrenia, using genome-wide data from the Psychiatric Genomics Consortium as discovery samples. We then examined the relationships between these polygenic risk scores and three separable EF components measured with a latent variable model. We also examined the relationship between genetic risk for ADHD and MDD and their respective symptom counts and lifetime diagnoses. We found no evidence for larger effect sizes for EFs as endophenotypes for psychiatric disorders. However, larger sample sizes will be important in examining this relationship further.
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Only one prior study used a polygenic score to examine mediation by cognitive measures on ADHD, and it failed to detect mediation.
“While candidate gene studies have previously looked at statistical mediation by cognitive measures on ADHD,33,34 only one used a polygenic score.35 They failed to detect mediation.”
From Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder (2018) · cites this paper as [35]
Benca et al. did not find reliable executive function mediation of polygenic score effects on ADHD, but their discovery and target samples were smaller.
“Benca et al35 failed to find reliable EF mediation of PGS effects on ADHD but had a smaller discovery and target sample.”
From Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder (2018) · cites this paper as [35]
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Nigg, J. T., Gustafsson, H. C., Karalunas, S. L., Ryabinin, P., McWeeney, S. K., Faraone, S. V., Mooney, M. A., Fair, D. A., & Wilmot, B. (2018) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2017.12.013 · Cited by 93 · see citing works
- Authors
- Benca, C. E., Derringer, J. L., Corley, R. P., Young, S. E., Keller, M. C., Hewitt, J. K., & Friedman, N. P.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- University of Colorado Boulder (US)
- University of Colorado Denver (US)
- ORCID
- Venue
- Behavior Genetics
- Published
- 2016-10-14
- Volume
- 47
- Issue
- 1
- Pages
- 11-24
- ISSN
- 0001-8244 (ISSN-L)
- 1573-3297
- PMC
- PMC5225028
- OpenAlex
- W2530737289
- Cited by
- 26
- References
- 56
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 1
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavior Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH063207, MH001865, MH016880, MH079485, DA011015, DA035804, AG046938, HD010333)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- executive function, polygenic risk score, endophenotypes, mental illness, autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, schizophrenia, Psychiatric Genomics Consortium, genetic risk, symptom count
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Cognition, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Intelligence, Male, Psychotic Disorders, Risk Factors, Task Performance and Analysis, Multifactorial Inheritance, Young Adult, Executive Function
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