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1. Epigenetics, gene expression, and stress in mothers and offspring in the Democratic Republic of Congo: A biocultural investigation of the intergenerational effects of stress

   Mulligan CJ, Maisha FM (January 2019, American journal of physical anthropology)

   The field of social and behavioral epigenetics examines how social and behavioral experiences can cause epigenetically-driven changes in gene expression that in turn influence health and well-being. We work in the eastern Democratic Republic of Congo, where 20 years of conflict and post-conflict violence have subjected women to extreme stress and sexual violence. We collected blood samples from mothers and their offspring at birth, plus follow-up samples from offspring up to five years of age, in three cohorts (2010 cohort, n=25; 2013 cohort , n=103, 2015 cohort, n=77). Using DNA extracted from blood and placental samples, we assayed methylation using Illumina’s 450K and EPIC chips, telomere length, and gene expression using the ClariomS chip. We also collected ethnographic and survey data on maternal stress, newborn health outcomes, and cortisol from offspring saliva and hair samples. Using these data, we tested for associations among maternal stress, DNA methylation, gene expression, and offspring health outcomes. We find that epigenetic aging is accelerated in mothers relative to chronological age, but newborn epigenetic age appears unchanged. In contrast, telomere length is significantly shorter in offspring born to mothers with high levels of war stress, but this effect only emerges after birth. Analyses of epigenome and gene expression data are ongoing. Our study takes a biocultural perspective to understand the molecular, biological, and health effects of stress and violence, particularly from an intergenerational perspective. 

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2. The Impact of a School-Based Academic Support Program on Students’ Psychosocial Impairment

   White, Gwyne W.; Hatchimonji, Danielle R.; Vaid, Esha; Caldwell Jr., Rickey A; Elias, Maurice J. (May 2023, Journal of educational and developmental psychology)

   The skills conveyed in high school are essential for success, and evidence suggests that psychosocial well-being is critical to that process. Advancement via Individual Determination (AVID) is an in-school, academic support program that targets underserved students. The current study explored the impact of an intervention program targeting academic achievement on student perceptions of social support and psychosocial impairment. The study was conducted in an under-resourced, majority Latinx high school and the sample included 75 AVID students and 140 demographically matched controls. Hierarchical linear regression analyses were performed to identify the impact of participation in the AVID program on symptoms of emotional and behavioral distress. After controlling for demographics factors and academic achievement, student perceptions of emotional and teacher support explained 7.2\% of the variance in psychosocial distress; participation in the AVID intervention was found to have significantly improved the variance accounted for (ΔR2=.02, 5.13, p=.025; R2=.11, F(9,204)=2.90, p=.003). The results of this study indicate that perceived teacher social support and AVID participation were, independently, significantly associated with reduced student psychosocial distress. These findings suggest that interventions targeting the complex mechanisms of school achievement may also have a positive impact on psychosocial impairment beyond student perceptions of social support. 

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3. Epigenetic drift underlies epigenetic clock signals, but displays distinct responses to lifespan interventions, development, and cellular dedifferentiation

   https://doi.org/10.18632/aging.205503  

   Bertucci-Richter, Emily M.; Shealy, Ethan P.; Parrott, Benjamin B. (January 2024, Aging)

   Changes in DNA methylation with age are observed across the tree of life. The stereotypical nature of these changes can be modeled to produce epigenetic clocks capable of predicting chronological age with unprecedented accuracy. Despite the predictive ability of epigenetic clocks and their utility as biomarkers in clinical applications, the underlying processes that produce clock signals are not fully resolved, which limits their interpretability. Here, we develop a computational approach to spatially resolve the within read variability or “disorder” in DNA methylation patterns and test if age-associated changes in DNA methylation disorder underlie signals comprising epigenetic clocks. We find that epigenetic clock loci are enriched in regions that both accumulate and lose disorder with age, suggesting a link between DNA methylation disorder and epigenetic clocks. We then develop epigenetic clocks that are based on regional disorder of DNA methylation patterns and compare their performance to other epigenetic clocks by investigating the influences of development, lifespan interventions, and cellular dedifferentiation. We identify common responses as well as critical differences between canonical epigenetic clocks and those based on regional disorder, demonstrating a fundamental decoupling of epigenetic aging processes. Collectively, we identify key linkages between epigenetic disorder and epigenetic clocks and demonstrate the multifaceted nature of epigenetic aging in which stochastic processes occurring at non-random loci produce predictable outcomes. 

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4. Epigenetic dynamics in infancy and the impact of maternal engagement

   https://doi.org/10.1126/sciadv.aay0680  

   Krol, Kathleen M.; Moulder, Robert G.; Lillard, Travis S.; Grossmann, Tobias; Connelly, Jessica J. (October 2019, Science Advances)

   The contribution of nature versus nurture to the development of human behavior has been debated for centuries. Here, we offer a piece to this complex puzzle by identifying the human endogenous oxytocin system—known for its critical role in mammalian sociality—as a system sensitive to its early environment and subject to epigenetic change. Recent animal work suggests that early parental care is associated with changes in DNA methylation of conserved regulatory sites within the oxytocin receptor gene ( OXTR m). Through dyadic modeling of behavior and OXTR m status across the first year and a half of life, we translated these findings to 101 human mother-infant dyads. We show that OXTR m is dynamic in infancy and its change is predicted by maternal engagement and reflective of behavioral temperament. We provide evidence for an early window of environmental epigenetic regulation of the oxytocin system, facilitating the emergence of individual differences in human behavior. 

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5. Potential Role of DNA Methylation as a Driver of Plastic Responses to the Environment Across Cells, Organisms, and Populations

   https://doi.org/10.1093/gbe/evae022  

   Bogan, Samuel N; Yi, Soojin V (February 2024, Genome Biology and Evolution)

   Hoffmann, Federico (Ed.)

   Abstract There is great interest in exploring epigenetic modifications as drivers of adaptive organismal responses to environmental change. Extending this hypothesis to populations, epigenetically driven plasticity could influence phenotypic changes across environments. The canonical model posits that epigenetic modifications alter gene regulation and subsequently impact phenotypes. We first discuss origins of epigenetic variation in nature, which may arise from genetic variation, spontaneous epimutations, epigenetic drift, or variation in epigenetic capacitors. We then review and synthesize literature addressing three facets of the aforementioned model: (i) causal effects of epigenetic modifications on phenotypic plasticity at the organismal level, (ii) divergence of epigenetic patterns in natural populations distributed across environmental gradients, and (iii) the relationship between environmentally induced epigenetic changes and gene expression at the molecular level. We focus on DNA methylation, the most extensively studied epigenetic modification. We find support for environmentally associated epigenetic structure in populations and selection on stable epigenetic variants, and that inhibition of epigenetic enzymes frequently bears causal effects on plasticity. However, there are pervasive confounding issues in the literature. Effects of chromatin-modifying enzymes on phenotype may be independent of epigenetic marks, alternatively resulting from functions and protein interactions extrinsic of epigenetics. Associations between environmentally induced changes in DNA methylation and expression are strong in plants and mammals but notably absent in invertebrates and nonmammalian vertebrates. Given these challenges, we describe emerging approaches to better investigate how epigenetic modifications affect gene regulation, phenotypic plasticity, and divergence among populations. 

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