A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

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




TekijätCzamara Darina, Tissink Elleke, Tuhkanen Johanna, Martins Jade, Awaloff Yvonne, Drake Amanda J., Khulan Batbayar, Palotie Aarno, Winter Sibylle M., Nemeroff Charles B., Craighead W. Edward, Dunlop Boadie W., Mayberg Helen S., Kinkead Becky, Mathew Sanjay J., Iosifescu Dan V., Neylan Thomas C., Heim Christine M., Lahti Jari, Eriksson Johan G., Räikkönen Katri, Ressler Kerry J., Provençal Nadine, Binder Elisabeth B.

KustantajaSPRINGER NATURE

Julkaisuvuosi2021

JournalTranslational Psychiatry

Tietokannassa oleva lehden nimiTRANSLATIONAL PSYCHIATRY

Lehden akronyymiTRANSL PSYCHIAT

Artikkelin numeroARTN 88

Vuosikerta11

Numero1

Sivujen määrä11

ISSN2158-3188

eISSN2158-3188

DOIhttps://doi.org/10.1038/s41398-020-01147-z

Verkko-osoitehttps://www.nature.com/articles/s41398-020-01147-z

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/53390059


Tiivistelmä
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 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 GxCA but almost never by CA alone. Across ages and tissues, 1672 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.

Ladattava julkaisu

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.





Last updated on 2024-26-11 at 10:58