Environmental Epigenetics最新文献

This review article provides a framework for the use of deoxyribonucleic acid (DNA) methylation (DNAm) biomarkers to study the biological embedding of socioeconomic position (SEP) and summarizes the latest developments in the area. It presents the emerging literature showing associations between individual- and neighborhood-level SEP exposures and DNAm across the life course. In contrast to questionnaire-based methods of assessing SEP, we suggest that DNAm biomarkers may offer an accessible metric to study questions about SEP and health outcomes, acting as a personal dosimeter of exposure. However, further work remains in standardizing SEP measures across studies and evaluating consistency across domains, tissue types, and time periods. Meta-analyses of epigenetic associations with SEP are offered as one approach to confirm the replication of DNAm loci across studies. The development of DNAm biomarkers of SEP would provide a method for examining its impact on health outcomes in a more robust way, increasing the rigor of epidemiological studies.

Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother-child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother-child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76-1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.

Breast cancer (BC) is the commonest human cancer and its incidence (BC incidence, BCI) is rising worldwide. Whilst both tobacco and alcohol have been linked to BCI genotoxic cannabinoids have not been investigated. Age-adjusted state-based BCI 2003-2017 was taken from the Surveillance Epidemiology and End Results database of the Centers for Disease Control. Drug use from the National Survey of Drug Use and Health, response rate 74.1%. Median age, median household income and ethnicity were from US census. Inverse probability weighted (ipw) multivariable regression conducted in R. In bivariate analysis BCI was shown to be significantly linked with rising cannabis exposure {β-est. = 3.93 [95% confidence interval 2.99, 4.87], P = 1.10 × 10^-15}. At 8 years lag cigarettes:cannabis [β-est. = 2660 (2150.4, 3169.3), P = 4.60 × 10^-22] and cannabis:alcoholism [β-est. = 7010 (5461.6, 8558.4), P = 1.80 × 10^-17] were significant in ipw-panel regression. Terms including cannabidiol [CBD; β-est. = 16.16 (0.39, 31.93), P = 0.446] and cannabigerol [CBG; β-est. = 6.23 (2.06, 10.39), P = 0.0034] were significant in spatiotemporal models lagged 1:2 years, respectively. Cannabis-liberal paradigms had higher BCI [67.50 ± 0.26 v. 65.19 ± 0.21/100 000 (mean ± SEM), P = 1.87 × 10^-11; β-est. = 2.31 (1.65, 2.96), P = 9.09 × 10^-12]. 55/58 expected values >1.25 and 13/58 >100. Abortion was independently and causally significant in space-time models. Data show that exposure to cannabis and the cannabinoids Δ9-tetrahydrocannabinol, CBD, CBG and alcoholism fulfil quantitative causal criteria for BCI across space and time. Findings are robust to adjustment for age and several known sociodemographic, socio-economic and hormonal risk factors and establish cannabinoids as an additional risk factor class for breast carcinogenesis. BCI is higher under cannabis-liberal legal paradigms.

Tossed about by the tides of history, the inheritance of acquired characteristics has found a safe harbor at last in the rapidly expanding field of epigenetics. The slow pace of genetic variation and high opportunity cost associated with maintaining a diverse genetic pool are well-matched by the flexibility of epigenetic traits, which can enable low-cost exploration of phenotypic space and reactive tuning to environmental pressures. Aiding in the generation of a phenotypically plastic population, epigenetic mechanisms often provide a hotbed of innovation for countering environmental pressures, while the potential for genetic fixation can lead to strong epigenetic-genetic evolutionary synergy. At the level of cells and cellular populations, we begin this review by exploring the breadth of mechanisms for the storage and intergenerational transmission of epigenetic information, followed by a brief review of common and exotic epigenetically regulated phenotypes. We conclude by offering an in-depth coverage of recent papers centered around two critical issues: the evolvability of epigenetic traits through Baldwinian adaptive phenotypic plasticity and the potential for synergy between epigenetic and genetic evolution.

Despite still being a matter of debate, there is growing evidence that pollutant-induced epigenetic changes can be propagated across generations. Whereas such modifications could have long-lasting effects on organisms and even on population, environmentally relevant data from long-term exposure combined with follow-up through multiple generations remain scarce for non-mammalian species. We performed a transgenerational experiment comprising four successive generations of zebrafish. Only fish from the first generation were exposed to an environmentally realistic concentration of cadmium (Cd). Using a whole methylome analysis, we first identified the DNA regions that were differentially methylated in response to Cd exposure and common to fish of the first two generations. Among them, we then focused our investigations on the exon 3 (ex3) of the cep19 gene. We indeed recorded transgenerational growth disorders in Cd-exposed fish, and a mutation in this exon is known to cause morbid obesity in mammals. Its methylation level was thus determined in zebrafish from all the four generations by means of a targeted and base resolution method. We observed a transgenerational inheritance of Cd-induced DNA methylation changes up to the fourth generation. However, these changes were closely associated with genetic variations, mainly a single nucleotide polymorphism. This single nucleotide polymorphism was itself at the origin of the creation or deletion of a methylation site and deeply impacted the methylation level of neighboring methylation sites. Cd-induced epigenetic changes were associated with different mRNA transcripts and an improved condition of Cd fish. Our results emphasize a tight relationship between genetic and epigenetic mechanisms and suggest that their interplay and pre-existing diversity can allow rapid adaptation to anthropogenic environmental changes.