UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

DRD4 methylation as a potential biomarker for physical aggression: An epigenome-wide, cross-tissue investigation

Cecil, C; Walton, E; Pingault, JB; Provencal, N; Pappa, I; Vitaro, F; Côté, S; ... McCrory, E; + view all (2018) DRD4 methylation as a potential biomarker for physical aggression: An epigenome-wide, cross-tissue investigation. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics , 117 (8) pp. 746-764. 10.1002/ajmg.b.32689. Green open access

[img]
Preview
Text
Cecil_etal_2018_AJMG_EWASaggression_SelfArchiving.pdf - Accepted version

Download (2MB) | Preview

Abstract

Epigenetic processes that regulate gene expression, such as DNA methylation (DNAm), have been linked to individual differences in physical aggression. Yet, it is currently unclear whether: (i) DNAm patterns in humans associate with physical aggression independently of other co-occurring psychiatric and behavioral symptoms; (ii) whether these patterns are observable across multiple tissues; and (iii) whether they may function as a causal vs noncausal biomarker of physical aggression. Here, we used a multi-sample, cross-tissue design to address these questions. First, we examined genome-wide DNAm patterns (buccal swabs; Illumina 450k) associated with engagement in physical fights in a sample of high-risk youth (n=119; age=16-24 years; 53% female). We identified one differentially methylated region in DRD4, which survived genome-wide correction, associated with physical aggression above and beyond co-occurring symptomatology (e.g. ADHD, substance use), and showed strong cross-tissue concordance with both blood and brain. Second, we found that DNAm sites within this region were also differentially methylated in an independent sample of young adults, between individuals with a history of chronic-high vs low physical aggression (peripheral T cells; ages 26–28). Finally, we ran a Mendelian randomization analysis using GWAS data from the EAGLE consortium to test for a causal association of DRD4 methylation with physical aggression. Only one genetic instrument was eligible for the analysis, and results provided no evidence for a causal association. Overall, our findings lend support for peripheral DRD4 methylation as a potential biomarker of physically aggressive behavior, with no evidence yet of a causal relationship.

Type: Article
Title: DRD4 methylation as a potential biomarker for physical aggression: An epigenome-wide, cross-tissue investigation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/ajmg.b.32689
Publisher version: https://doi.org/10.1002/ajmg.b.32689
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: DNA methylation; physical aggression; DRD4; externalizing problems; replication; Mendelian randomization
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology
URI: https://discovery.ucl.ac.uk/id/eprint/10058054
Downloads since deposit
31Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item