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DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.

Publication ,  Journal Article
van Dongen, J; Hagenbeek, FA; Suderman, M; Roetman, PJ; Sugden, K; Chiocchetti, AG; Ismail, K; Mulder, RH; Hafferty, JD; Adams, MJ; Walker, RM ...
Published in: Molecular psychiatry
June 2021

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

June 2021

Volume

26

Issue

6

Start / End Page

2148 / 2162

Related Subject Headings

  • Young Adult
  • Psychiatry
  • Middle Aged
  • Longevity
  • Humans
  • Genome-Wide Association Study
  • Epigenome
  • Epigenesis, Genetic
  • DNA Methylation
  • CpG Islands
 

Citation

APA
Chicago
ICMJE
MLA
NLM
van Dongen, J., Hagenbeek, F. A., Suderman, M., Roetman, P. J., Sugden, K., Chiocchetti, A. G., … Boomsma, D. I. (2021). DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan. Molecular Psychiatry, 26(6), 2148–2162. https://doi.org/10.1038/s41380-020-00987-x
Dongen, Jenny van, Fiona A. Hagenbeek, Matthew Suderman, Peter J. Roetman, Karen Sugden, Andreas G. Chiocchetti, Khadeeja Ismail, et al. “DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.Molecular Psychiatry 26, no. 6 (June 2021): 2148–62. https://doi.org/10.1038/s41380-020-00987-x.
van Dongen J, Hagenbeek FA, Suderman M, Roetman PJ, Sugden K, Chiocchetti AG, et al. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan. Molecular psychiatry. 2021 Jun;26(6):2148–62.
van Dongen, Jenny, et al. “DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.Molecular Psychiatry, vol. 26, no. 6, June 2021, pp. 2148–62. Epmc, doi:10.1038/s41380-020-00987-x.
van Dongen J, Hagenbeek FA, Suderman M, Roetman PJ, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty JD, Adams MJ, Walker RM, Morris SW, Lahti J, Küpers LK, Escaramis G, Alemany S, Jan Bonder M, Meijer M, Ip HF, Jansen R, Baselmans BML, Parmar P, Lowry E, Streit F, Sirignano L, Send TS, Frank J, Jylhävä J, Wang Y, Mishra PP, Colins OF, Corcoran DL, Poulton R, Mill J, Hannon E, Arseneault L, Korhonen T, Vuoksimaa E, Felix JF, Bakermans-Kranenburg MJ, Campbell A, Czamara D, Binder E, Corpeleijn E, Gonzalez JR, Grazuleviciene R, Gutzkow KB, Evandt J, Vafeiadi M, Klein M, van der Meer D, Ligthart L, BIOS Consortium, Kluft C, Davies GE, Hakulinen C, Keltikangas-Järvinen L, Franke B, Freitag CM, Konrad K, Hervas A, Fernández-Rivas A, Vetro A, Raitakari O, Lehtimäki T, Vermeiren R, Strandberg T, Räikkönen K, Snieder H, Witt SH, Deuschle M, Pedersen NL, Hägg S, Sunyer J, Franke L, Kaprio J, Ollikainen M, Moffitt TE, Tiemeier H, van IJzendoorn MH, Relton C, Vrijheid M, Sebert S, Jarvelin M-R, Caspi A, Evans KL, McIntosh AM, Bartels M, Boomsma DI. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan. Molecular psychiatry. 2021 Jun;26(6):2148–2162.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

June 2021

Volume

26

Issue

6

Start / End Page

2148 / 2162

Related Subject Headings

  • Young Adult
  • Psychiatry
  • Middle Aged
  • Longevity
  • Humans
  • Genome-Wide Association Study
  • Epigenome
  • Epigenesis, Genetic
  • DNA Methylation
  • CpG Islands