Combined effects of genotype and childhood adversity shape variability of DNA methylation across age

  1. Czamara, Darina ORCID logo
  2. Tissink, Elleke ORCID logo
  3. Tuhkanen, Johanna
  4. Martins, Jade ORCID logo
  5. Awaloff, Yvonne
  6. drake, amanda ORCID logo
  7. Khulan, Batbayar
  8. Palotie, Aarno
  9. Winter, Sibylle M.
  10. Nemeroff, Charles B.
  11. Craighead, W. Edward ORCID logo
  12. Dunlop, Boadie ORCID logo
  13. Mayberg, Helen S.
  14. Kinkead, Becky ORCID logo
  15. Mathew, Sanjay ORCID logo
  16. Iosifescu, Dan V.
  17. Neylan, Thomas C.
  18. Heim, Christine ORCID logo
  19. Lahti, Jari ORCID logo
  20. Eriksson, Johan G.
  21. Räikkönen, Katri
  22. Ressler, Kerry ORCID logo
  23. Provençal, Nadine
  24. Binder, Elisabeth ORCID logo

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WeightNameValue
1000 Titel
  • Combined effects of genotype and childhood adversity shape variability of DNA methylation across age
1000 Autor/in
  1. Czamara, Darina |
  2. Tissink, Elleke |
  3. Tuhkanen, Johanna |
  4. Martins, Jade |
  5. Awaloff, Yvonne |
  6. drake, amanda |
  7. Khulan, Batbayar |
  8. Palotie, Aarno |
  9. Winter, Sibylle M. |
  10. Nemeroff, Charles B. |
  11. Craighead, W. Edward |
  12. Dunlop, Boadie |
  13. Mayberg, Helen S. |
  14. Kinkead, Becky |
  15. Mathew, Sanjay |
  16. Iosifescu, Dan V. |
  17. Neylan, Thomas C. |
  18. Heim, Christine |
  19. Lahti, Jari |
  20. Eriksson, Johan G. |
  21. Räikkönen, Katri |
  22. Ressler, Kerry |
  23. Provençal, Nadine |
  24. Binder, Elisabeth |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-02-01
1000 Erschienen in
1000 Quellenangabe
  • 11(1):88
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41398-020-01147-z |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851167/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms, but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DNAm at birth is best explained by the joint effects of genotype and prenatal environment. Here, we extend these analyses to postnatal stressors. We investigated the contribution of CA, cis genotype (G), and their additive (G+CA) and interactive (GxCA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1,074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA, which was assessed retrospectively using self-reports or verified through social services and registries. For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G+CA or GxCA but almost never by CA alone. Across ages and tissues, 1,672 DNAm sites showed consistency of the best model in all five cohorts, with GxCA interactions explaining most variance. The consistent GxCA sites mapped to genes enriched in brain-specific transcripts and Gene Ontology terms related to development and synaptic function. Interaction of CA with genotypes showed the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.
1000 Sacherschließung
lokal Infant, Newborn [MeSH]
lokal Female [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Retrospective Studies [MeSH]
lokal Epigenesis, Genetic [MeSH]
lokal Article
lokal DNA Methylation [MeSH]
lokal Genotype [MeSH]
lokal Psychology
lokal Psychiatric disorders
lokal Epigenomics [MeSH]
lokal Pregnancy [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-7381-904X|https://orcid.org/0000-0003-4225-9347|https://frl.publisso.de/adhoc/uri/VHVoa2FuZW4sIEpvaGFubmE=|https://orcid.org/0000-0001-6528-8947|https://frl.publisso.de/adhoc/uri/QXdhbG9mZiwgWXZvbm5l|https://orcid.org/0000-0001-8633-333X|https://frl.publisso.de/adhoc/uri/S2h1bGFuLCBCYXRiYXlhcg==|https://frl.publisso.de/adhoc/uri/UGFsb3RpZSwgQWFybm8=|https://frl.publisso.de/adhoc/uri/V2ludGVyLCBTaWJ5bGxlIE0u|https://frl.publisso.de/adhoc/uri/TmVtZXJvZmYsIENoYXJsZXMgQi4=|https://orcid.org/0000-0001-9957-0027|https://orcid.org/0000-0002-4653-0483|https://frl.publisso.de/adhoc/uri/TWF5YmVyZywgSGVsZW4gUy4=|https://orcid.org/0000-0003-0169-6989|https://orcid.org/0000-0002-2715-6641|https://frl.publisso.de/adhoc/uri/SW9zaWZlc2N1LCBEYW4gVi4=|https://frl.publisso.de/adhoc/uri/TmV5bGFuLCBUaG9tYXMgQy4=|https://orcid.org/0000-0002-6580-6326|https://orcid.org/0000-0002-4310-5297|https://frl.publisso.de/adhoc/uri/RXJpa3Nzb24sIEpvaGFuIEcu|https://frl.publisso.de/adhoc/uri/UsOkaWtrw7ZuZW4sIEthdHJp|https://orcid.org/0000-0002-5158-1103|https://frl.publisso.de/adhoc/uri/UHJvdmVuw6dhbCwgTmFkaW5l|https://orcid.org/0000-0001-7088-6618
1000 Hinweis
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1000 Erstellt am 2023-04-26T14:54:01.730+0200
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