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Cited by 36Epigenetics and DNA MethylationChild Abuse and TraumaBullying, Victimization, and Aggression

DNA methylation signatures of adolescent victimization: analysis of a longitudinal monozygotic twin sample

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Kandaswamy, Radhika, Hannon, Eilis, Arseneault, Louise, Mansell, Georgina, Sugden, Karen, Williams, Benjamin, Burrage, Joe, Staley, James R +7 more·2021·Epigenetics
DOI 10.1080/15592294.2020.1853317PMC PMC8813077
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Abstract

Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P < 5e-05), with altered DNAm trajectories between ages 10–18 associated with severe adolescent victimization (∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (∆Beta range = −2.2%−3.4%) and 42 buccal (∆Beta range = −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in LGR6 and ANK3 (Šidák P = 5e-09 and 4.07e-06), and one upstream of CCL27 (Šidák P = 2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.

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  • Differential DNA methylation profiles are associated with exposure to childhood adversity and cannabis use.

    “Indeed, recent parallel evidence suggests that differential DNAm profiles are associated with exposure to childhood adversity (CA) as well as cannabis use (CU) (Kandaswamy et al., 2020; Markunas et al., 2020; Nöthling, Malan-Müller, Abrahams, Hemmings, & Seedat, 2020).”

    From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Kandaswamy et al., 2020

    The Results and Discussion report suggestive DNA-methylation differences associated with severe adolescent victimization, supporting the childhood-adversity part of the sentence. The paper does not report an association with cannabis use, and its findings concern adolescent victimization rather than childhood adversity broadly. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Childhood adversity is associated with DNA methylation changes both in the general population and in clinical samples with a psychiatric diagnosis.

    “In addition, CA is associated with DNAm changes both in the general population (Kandaswamy et al., 2020) as well as in clinical samples with a psychiatric diagnosis (Online Supplementary Table S1 (SM)).”

    From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Kandaswamy et al., 2020

    The Study cohort and Results sections (pages unavailable) describe a community twin cohort and report suggestive DNA-methylation differences associated with severe adolescent victimization. This supports the general-population association, but the study specifically excluded participants with severe childhood victimization; its own findings do not establish the claimed association for childhood adversity. The clinical-sample clause is attributed to a different source, not Kandaswamy et al. (LLM, conf=0.84)

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Authors
Kandaswamy, R., Hannon, E., Arseneault, L., Mansell, G., Sugden, K., Williams, B., Burrage, J., Staley, J. R., Pishva, E., Dahir, A., Roberts, S., Danese, A., Mill, J., Fisher, H. L., & Wong, C. C. Y.
Affiliations
  • King's College London (GB)
  • University of Exeter (GB)
  • Duke University (US)
  • University of Bristol (GB)
Corresponding author
Fisher, Helen L
ORCID
Venue
Epigenetics
Publisher
Informa UK Limited
Published
2020-12-29
Volume
16
Issue
11
Pages
1169-1186
ISSN
  • 1559-2294 (ISSN-L)
  • 1559-2308
DOI
10.1080/15592294.2020.1853317
PMC
PMC8813077
OpenAlex
W3096350653
Cited by
36
References
77
Citations by year
2026: 5 · 2025: 10 · 2024: 10 · 2023: 6 · 2022: 4 · 2021: 1
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Epigenetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Economic and Social Research Council (ES/N000277/1, ES/S012567/1)
  • MQ: Transforming Mental Health (MQ14F40)
  • Medical Research Council (MR/M025020/1, G1002190)
  • National Institute of Child Health and Human Development (HD077482)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
  • Social Sciences › Psychology › Social Psychology › Bullying, Victimization, and Aggression
Keywords
adolescent victimization, DNA methylation, epigenome-wide association study, monozygotic twins, differentially methylated regions, LGR6, ANK3, CCL27, buccal DNA, blood DNA, childhood adversity
MeSH terms
Adolescent, Child, Cross-Sectional Studies, Humans, Twins, Monozygotic, DNA Methylation, Crime Victims, Epigenesis, Genetic, Genome-Wide Association Study, Epigenomics

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