Gene set enrichment analysis to create polygenic scores: a developmental examination of aggression
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Previous approaches for creating polygenic risk scores (PRSs) do not explicitly consider the biological or developmental relevance of the genetic variants selected for inclusion. We applied gene set enrichment analysis to meta-GWAS data to create developmentally targeted, functionally informed PRSs. Using two developmentally matched meta-GWAS discovery samples, separate PRSs were formed, then examined in time-varying effect models of aggression in a second, longitudinal sample of children (n = 515, 49% female) in early childhood (2–5 years old), and middle childhood (7.5–10.5 years old). Functional PRSs were associated with aggression in both the early and middle childhood models.
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The all-PRS and mapped-PRS (from SNPs mapped to gene sets using GSEA) were not significantly associated with aggression at any age.
“The all-PRS and mapped-PRS (from SNPs mapped to gene sets using GSEA) were not significantly associated with aggression at any age.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Elam [115]
The functional-PRS (SNPs from gene sets and with known biological function) was associated with aggression in both early and middle childhood.
“The functional-PRS (SNPs from gene sets and with known biological function) was associated with aggression in both early and middle childhood.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Elam [115]
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Freitag, E. W., Kelsey, C. M., Filho, E. J. D. M., Pokhvisneva, I., Patel, S. H., Silveira, P. P., Enlow, M. B., & Nelson, C. A. (2025) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.14140
Ouellet‐Morin, I., Geoffroy, M., Louis, P., Александрович, В. И., Morneau‐Vaillancourt, G., Langevin, R., Collin‐Vézina, D., Giguère, C., Bouliane, M., Petitclerc, A., et al. (2025) · Development and Psychopathology · doi:10.1017/s0954579425100801
- Authors
- Elam, K. K., Clifford, S., Shaw, D. S., Wilson, M. N., & Lemery-Chalfant, K.
- Affiliations
- Indiana University Bloomington (US)
- Arizona State University (US)
- University of Pittsburgh (US)
- University of Virginia (US)
- Corresponding author
- Elam, Kit K.
- Venue
- Translational Psychiatry
- Published
- 2019-09-02
- Volume
- 9
- Issue
- 1
- Pages
- 212-212
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6718657
- OpenAlex
- W2971554076
- Cited by
- 23
- References
- 75
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 3
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- IUScholarWorks Open (Indiana University) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (K01DA042828, DA022773, DA023245, DA036832)
- U.S. Department of Health & Human Services | NIH | Office of Behavioral and Social Sciences Research (K01DA042828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- polygenic risk score, gene set enrichment analysis, aggression, child development, functional variants, meta-GWAS, early childhood, middle childhood, developmental trajectories
- MeSH terms
- Aggression, Child, Child, Preschool, Female, Humans, Male, Phenotype, Risk Factors, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide
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