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Author Notes:

Darina Czamara, Email: darina@psych.mpg.de

The authors would like to thank all study participants as well as all involved in the HBCS. The authors also acknowledge the Genetics Core of the Wellcome Trust Clinical Research Facility (Edinburgh, UK) which used the 450K array for the HBCS samples.

See publication for full list of authors and disclosures.


Research Funding:

The PReDICT study was supported by the following National Institutes of Health grants: P50 MH077083; R01 MH080880; UL1 RR025008; and M01 RR0039. Funding for the U19 study was provided from a grant from the National Institute of Mental Health, U19 MH069056, with additional support from VA CSRD Project ID 09S-NIMH-002. The GRADY study was supported by a grant from the National Institute of Mental Health, R01 MH071537-01A1. HBCS has been supported by grants from the British Heart Foundation, Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, and the Emil Aaltonen Foundation. The BerlinLCS study was funded by a research grant from the German Federal Ministry of Education and Research (BMBF) to CMH and EBB (FKZ 01KR1301B). AJD has received a Scottish Senior Clinical Fellowship (SCD/09).

Open Access funding enabled and organized by Projekt DEAL.


  • Psychiatric disorders
  • Psychology

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

Journal Title:

Translational Psychiatry


Volume 11


Type of Work:

Article | Final Publisher PDF


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 (G × CA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1074 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 G × CA but almost never by CA alone. Across ages and tissues, 1672 DNAm sites showed consistency of the best model in all five cohorts, with G × CA interactions explaining most variance. The consistent G × CA 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.

Copyright information:

© The Author(s) 2021

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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