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.
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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 > 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 |
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