TY  - JOUR
PY  - 2018//
TI  - DRD4 methylation as a potential biomarker for physical aggression: an epigenome-wide, cross-tissue investigation
JO  - American journal of medical genetics. part B, neuropsychiatric genetics
A1  - Cecil, Charlotte A. M.
A1  - Walton, Esther
A1  - Pingault, Jean-Baptiste
A1  - Provençal, Nadine
A1  - Pappa, Irene
A1  - Vitaro, Frank
A1  - Côté, Sylvana
A1  - Szyf, Moshe
A1  - Tremblay, Richard E.
A1  - Tiemeier, Henning
A1  - Viding, Essi
A1  - McCrory, Eamon J.
SP  - 746
EP  - 764
VL  - 177
IS  - 8
N2  - 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: (a) DNAm patterns in humans associate with physical aggression independently of other co-occurring psychiatric and behavioral symptoms; (b) whether these patterns are observable across multiple tissues; and (c) whether they may function as a causal versus noncausal biomarker of physical aggression. Here, we used a multisample, 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 versus 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.<br><br>© 2018 Wiley Periodicals, Inc.<p />  <p>Language: en</p>
LA  - en
SN  - 1552-4841
UR  - http://dx.doi.org/10.1002/ajmg.b.32689
ID  - ref1
ER  -