Home and Epigenome:Exploring the Role of DNA Methylation in the Relationship Between Poor Housing Quality and Depressive Symptoms

Introduction Poor housing quality associates with risk for depression. However, previous research often lacks consideration of socioeconomic status (SES) baseline depressive symptoms and biological processes, leading to concerns of confounding and reverse causation.Methods In a sample of up to 9669 adults, we investigated cross-sectional and longitudinal associations between housing quality (assessed at age 28, 1-year and 2 year follow-ups) and depressive symptoms (at four intervals between enrolment and 18-year follow-up). In subsamples (n=871, n=731), we investigated indirect effects via DNA methylation.Results Poor housing quality associated with depressive symptoms cross-sectionally (beta range: 0.02–0.06) after controlling for SES and other factors. Longitudinally, this association persisted at the ~2 year, but not the ~18-year follow-up period. Indirect effects (β=0.002–0.012) linked to genes related to ageing, obesity and brain health.Conclusion These results highlight poor housing quality as a risk factor for depression and the potential role of DNA methylation in this association

Home and Epigenome:Exploring the Role of DNA Methylation in the Relationship Between Poor Housing Quality and Depressive Symptoms

Introduction Poor housing quality associates with risk for depression. However, previous research often lacks consideration of socioeconomic status (SES) baseline depressive symptoms and biological processes, leading to concerns of confounding and reverse causation.Methods In a sample of up to 9669 adults, we investigated cross-sectional and longitudinal associations between housing quality (assessed at age 28, 1-year and 2 year follow-ups) and depressive symptoms (at four intervals between enrolment and 18-year follow-up). In subsamples (n=871, n=731), we investigated indirect effects via DNA methylation.Results Poor housing quality associated with depressive symptoms cross-sectionally (beta range: 0.02–0.06) after controlling for SES and other factors. Longitudinally, this association persisted at the ~2 year, but not the ~18-year follow-up period. Indirect effects (β=0.002–0.012) linked to genes related to ageing, obesity and brain health.Conclusion These results highlight poor housing quality as a risk factor for depression and the potential role of DNA methylation in this association

Home and Epigenome:Exploring the Role of DNA Methylation in the Relationship Between Poor Housing Quality and Depressive Symptoms

Introduction Poor housing quality associates with risk for depression. However, previous research often lacks consideration of socioeconomic status (SES) baseline depressive symptoms and biological processes, leading to concerns of confounding and reverse causation.Methods In a sample of up to 9669 adults, we investigated cross-sectional and longitudinal associations between housing quality (assessed at age 28, 1-year and 2 year follow-ups) and depressive symptoms (at four intervals between enrolment and 18-year follow-up). In subsamples (n=871, n=731), we investigated indirect effects via DNA methylation.Results Poor housing quality associated with depressive symptoms cross-sectionally (beta range: 0.02–0.06) after controlling for SES and other factors. Longitudinally, this association persisted at the ~2 year, but not the ~18-year follow-up period. Indirect effects (β=0.002–0.012) linked to genes related to ageing, obesity and brain health.Conclusion These results highlight poor housing quality as a risk factor for depression and the potential role of DNA methylation in this association

Prenatal Alcohol Exposure: Profiling Developmental DNA Methylation Patterns in Central and Peripheral Tissues

Background: Prenatal alcohol exposure (PAE) can alter the development of neurobiological systems, leading to lasting neuroendocrine, neuroimmune, and neurobehavioral deficits. Although the etiology of this reprogramming remains unknown, emerging evidence suggests DNA methylation as a potential mediator and biomarker for the effects of PAE due to its responsiveness to environmental cues and relative stability over time. Here, we utilized a rat model of PAE to examine the DNA methylation profiles of rat hypothalami and leukocytes at four time points during early development to assess the genome-wide impact of PAE on the epigenome and identify potential biomarkers of PAE. Our model of PAE resulted in blood alcohol levels of ~80–150 mg/dl throughout the equivalent of the first two trimesters of human pregnancy. Hypothalami were analyzed on postnatal days (P) 1, 8, 15, 22 and leukocytes at P22 to compare central and peripheral markers. Genome-wide DNA methylation analysis was performed by methylated DNA immunoprecipitation followed by next-generation sequencing.Results: PAE resulted in lasting changes to DNA methylation profiles across all four ages, with 118 differentially methylated regions (DMRs) displaying persistent alterations across the developmental period at a false-discovery rate (FDR) < 0.05. In addition, 299 DMRs showed the same direction of change in the hypothalamus and leukocytes of P22 pups at an FDR < 0.05, with some genes overlapping with the developmental profile findings. The majority of these DMRs were located in intergenic regions, which contained several computationally-predicted transcription factor binding sites. Differentially methylated genes were generally involved in immune function, epigenetic remodeling, metabolism, and hormonal signaling, as determined by gene ontology analyses.Conclusions: Persistent DNA methylation changes in the hypothalamus may be associated with the long-term physiological and neurobehavioral alterations in observed in PAE. Furthermore, correlations between epigenetic alterations in peripheral tissues and those in the brain will provide a foundation for the development of biomarkers of fetal alcohol spectrum disorder (FASD). Finally, findings from studies of PAE provide important insight into the etiology of neurodevelopmental and mental health disorders, as they share numerous phenotypes and comorbidities

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence:Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

BackgroundChildhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study.MethodsWe first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years.FindingsOf 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence.InterpretationThese findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity

Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays:lessons learned for clinical and longitudinal studies

DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1 (EPICv1) and 450K arrays. Whether DNAm measurements are stable across these three generations of arrays has yet not been investigated, limiting the ability of researchers—especially those with longitudinal data—to compare and replicate results across arrays. Here, we present results from a study of 30 child participants (15 male; 15 female) from the Drakenstein Child Health Study, who had DNAm measured on all three of the latest arrays: 450K, EPICv1, and EPICv2. Using these data, we created an annotation of probe quality across arrays, which includes the intraclass correlations, interquartile ranges, correlations, and array bias (i.e., the extent to which DNAm levels were explained by array type) of all CpGs. We also present results from an analysis of sex differences, where we found that CpGs with lower replicability across arrays had higher array-based variance, suggesting this variance metric help guide replication efforts. We also showed that epigenetic age estimates across arrays were more stable when using the principal component versions of epigenetic clocks. Ultimately, this collection of results provides a framework for investigating the replicability and longitudinal stability of epigenetic changes across multiple versions of Illumina DNAm arrays.</p

Stress reactivity moderates the association between stressful life events and depressive symptoms in adolescents: Results from a population-based study

A large body of evidence links stressful life events with depression. However, little is understood about the role of perceived impact in this association. We performed regression analysis to investigate whether self-reported stress reactivity (derived by regressing the impact-weighted life event score on the unweighted score) moderated the association between stressful life events and depressive symptoms in adolescents from the Avon Longitudinal Study of Parents and Children cohort (n = 4791), controlling for age at outcome, sex, ethnicity, and maternal education. Depressive symptoms were assessed using the self-report Short Mood and Feelings Questionnaire (score range 0-26) at 16 years of age. Adolescents also reported on their exposure to 23 possible stressful life events since age 12 and their impact, which were used to define stress reactivity groups using a residual regression approach. We identified a moderating effect of stress reactivity. Adolescents with high stress reactivity showed a stronger association between the number of stressful life events and depressive symptoms than adolescents with low (b = 0.32, 95 % CI = 0.13, 0.50, p < 0.001) or typical (b = 0.44, 95 % CI = 0.28, 0.60, p < 0.001) stress reactivity. Limitations include the use of retrospective life event measures and limited generalisability of findings to other population-based, high-risk, or clinical samples. When resources are limited, interventions should prioritise individuals with high stress reactivity who have experienced multiple stressful life events, as these individuals may be at greater risk for depression. [Abstract copyright: Copyright © 2024. Published by Elsevier B.V.