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Effect of polygenic risk scores on depression in childhood trauma
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Background: Research on gene×environment interaction in major depressive disorder (MDD) has thus far primarily focused on candidate genes, although genetic effects are known to be polygenic. Aims: To test whether the effect of polygenic risk scores on MDD is moderated by childhood trauma. Method: The study sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340 screened controls from The Netherlands. Chronic or remitted episodes (severe MDD) were present in 956 participants. The occurrence of childhood trauma was assessed with the Childhood Trauma Interview and the polygenic risk scores were based on genome-wide meta-analysis results from the Psychiatric Genomics Consortium. Results: The polygenic risk scores and childhood trauma independently affected MDD risk, and evidence was found for interaction as departure from both multiplicativity and additivity, indicating that the effect of polygenic risk scores on depression is increased in the presence of childhood trauma. The interaction effects were similar in predicting all MDD risk and severe MDD risk, and explained a proportion of variation in MDD risk comparable to the polygenic risk scores themselves. Conclusions: The interaction effect found between polygenic risk scores and childhood trauma implies that (1) studies on direct genetic effect on MDD gain power by focusing on individuals exposed to childhood trauma, and that (2) individuals with both high polygenic risk scores and exposure to childhood trauma are particularly at risk for developing MDD.
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“Polygenic risk scores have been investigated as modifiers of depression risk with both childhood adversity (Peyrot et al. 2014; Mullins et al. 2016) and adult stressful events (Mullins et al. 2016) with inconsistent results.”
From Childhood adversity, adult stress, and the risk of major depression or generalized anxiety disorder in US soldiers: a test of the stress sensitization hypothesis (2017) · cites this paper as Peyrot et al. 2014
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Metadata
- Authors
- Peyrot, W. J., Milaneschi, Y., Abdellaoui, A., Sullivan, P. F., Hottenga, J. J., Boomsma, D. I., & Penninx, B. W. J. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Peyrot, Wouter J.
- ORCID
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2014-08
- Volume
- 205
- Issue
- 2
- Pages
- 113-119
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- PMC
- PMC4118052
- OpenAlex
- W2149016179
- Cited by
- 209
- References
- 39
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 15 · 2023: 13 · 2022: 20 · 2021: 17 · 2020: 28 · 2019: 31 · 2018: 22 · 2017: 19 · 2016: 13 · 2015: 9 · 2014: 2
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Vrije Universiteit Amsterdam
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (10-000-1002, NWO 480‐05‐003, 480- 05-003)
- GGZ inGeest
- Centre for Medical Systems Biology
- University of North Carolina at Chapel Hill
- National Institute of Mental Health (MH080403, U01MH085520, HEALTH-F4-2007-201413, MH085520, RC2MH089951, R01MH080403)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- polygenic risk score, childhood trauma, major depressive disorder, gene-environment interaction, severe depression, genetic risk, Psychiatric Genomics Consortium
- MeSH terms
- Adult, Child, Child Abuse, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Longitudinal Studies, Male, Middle Aged, Netherlands, Risk Factors, Case-Control Studies, Risk Assessment, Genetic Predisposition to Disease, Adult Survivors of Child Abuse, Gene-Environment Interaction
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