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Combined effects of genotype and childhood adversity shape variability of DNA methylation across age
- Source :
- Translational Psychiatry, 11:88. Nature Publishing Group, Translational Psychiatry, Vol 11, Iss 1, Pp 1-11 (2021), Czamara, D, Tissink, E, Tuhkanen, J, Martins, J, Awaloff, Y, Drake, A J, Khulan, B, Palotie, A, Winter, S M, Nemeroff, C B, Craighead, W E, Dunlop, B W, Mayberg, H S, Kinkead, B, Mathew, S J, Iosifescu, D V, Neylan, T C, Heim, C M, Lahti, J, Eriksson, J G, Räikkönen, K, Ressler, K J, Provençal, N & Binder, E B 2021, ' Combined effects of genotype and childhood adversity shape variability of DNA methylation across age ', Translational Psychiatry, vol. 11, 88 . https://doi.org/10.1038/s41398-020-01147-z, Translational Psychiatry, Czamara, D, Tissink, E, Tuhkanen, J, Martins, J, Awaloff, Y, Drake, A J, Batbayar, K, Palotie, A, Winter, S M, Nemeroff, C B, Craighead, E, Dunlop, B W, Mayberg, H S, Kinkead, B, Mathew, S J, Iosifescu, D V, Neylan, T C, Heim, C M, Lahti, J, Eriksson, J G, Räikkönen, K, Ressler, K J, Provencal, N & Binder, E B 2021, ' Combined effects of genotype and childhood adversity shape variability of DNA methylation across age ', Translational Psychiatry . https://doi.org/10.1038/s41398-020-01147-z
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Adult
Epigenomics
0301 basic medicine
Genotype
Biology
Article
3124 Neurology and psychiatry
Epigenesis, Genetic
lcsh:RC321-571
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Pregnancy
Humans
Psychology
Epigenetics
Gene
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Biological Psychiatry
Retrospective Studies
Genetics
Human studies
Infant, Newborn
dNaM
DNA Methylation
Psychiatry and Mental health
Synaptic function
030104 developmental biology
DNA methylation
Disease risk
Female
Psychiatric disorders
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 21583188
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry, 11:88. Nature Publishing Group, Translational Psychiatry, Vol 11, Iss 1, Pp 1-11 (2021), Czamara, D, Tissink, E, Tuhkanen, J, Martins, J, Awaloff, Y, Drake, A J, Khulan, B, Palotie, A, Winter, S M, Nemeroff, C B, Craighead, W E, Dunlop, B W, Mayberg, H S, Kinkead, B, Mathew, S J, Iosifescu, D V, Neylan, T C, Heim, C M, Lahti, J, Eriksson, J G, Räikkönen, K, Ressler, K J, Provençal, N & Binder, E B 2021, ' Combined effects of genotype and childhood adversity shape variability of DNA methylation across age ', Translational Psychiatry, vol. 11, 88 . https://doi.org/10.1038/s41398-020-01147-z, Translational Psychiatry, Czamara, D, Tissink, E, Tuhkanen, J, Martins, J, Awaloff, Y, Drake, A J, Batbayar, K, Palotie, A, Winter, S M, Nemeroff, C B, Craighead, E, Dunlop, B W, Mayberg, H S, Kinkead, B, Mathew, S J, Iosifescu, D V, Neylan, T C, Heim, C M, Lahti, J, Eriksson, J G, Räikkönen, K, Ressler, K J, Provencal, N & Binder, E B 2021, ' Combined effects of genotype and childhood adversity shape variability of DNA methylation across age ', Translational Psychiatry . https://doi.org/10.1038/s41398-020-01147-z
- Accession number :
- edsair.doi.dedup.....b0fd010272639f82906e7e4ccc2b7b16