Epigenetic Research Research Articles

Epigenetics and ADHD.

There is robust evidence of genetic susceptibility to Attention-Deficit Hyperactivity Disorder (ADHD); however, there still remains significant variability that is not attributable to genetic factors. The emerging field of epigenetics is beginning to reveal how genotypic expression can be mediated by an array of variables including external environmental exposure, inter-individual developmental variation, and by the genome itself. Epigenetic modification plays a central role in neurobiological and developmental processes, and disturbances to these processes can have implications for a range of mental health problems. Although the field is still in its early days, this chapter will discuss the current standing of epigenetic research into ADHD. Firstly, key relevant epigenetic processes will be discussed. This will be followed by an overview of the key findings to date investigating the role of epigenetics in ADHD. Human studies have included the theory-driven approach of candidate-gene studies (CGS), as well as the increasingly popular exploratory approach of epigenome-wide association studies (EWAS). Overall, the findings are heterogeneous. However, it is possible that with more longitudinal studies and better characterised cohorts, both predictive and protective links between epigenetic processes and ADHD will be revealed.

The Neuroepigenetic Landscape of Vertebrate and Invertebrate Models of Neurodegenerative Diseases.

Vertebrate and invertebrate models of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, have been paramount to our understanding of the pathophysiology of these conditions; however, the brain epigenetic landscape is less well established in these disease models. DNA methylation, histone modifications, and microRNAs are among commonly studied mechanisms of epigenetic regulation. Genome-wide studies and candidate studies of specific methylation marks, histone marks, and microRNAs have demonstrated the dysregulation of these mechanisms in models of neurodegenerative diseases; however, the studies to date are scarce and inconclusive and the implications of many of these changes are still not fully understood. In this review, we summarize epigenetic changes reported to date in the brain of vertebrate and invertebrate models used to study neurodegenerative diseases, specifically diseases affecting the aging population. We also discuss caveats of epigenetic research so far and the use of disease models to understand neurodegenerative diseases, with the aim of improving the use of model organisms in this context in future studies.

Global Trends in Atherosclerosis Research in the Epigenetics Field: Bibliometric and Visualization Studies.

Atherosclerosis is a pathological vascular state caused by the interaction of environmental and hereditary factors. Epigenetic modifications may be the bridge connecting environmental factors and genetic factors. A search for publications on the Web of Science database in the field of atherosclerosis related to epigenetics was conducted from the earliest mention to 31 December 2020. Data on total and annual publications, citations, impact factors, Hirsch (H)-index, citation times, most prolific authors, and frequently published journals were collected for quantitative and qualitative comparison. A total of 1848 publications related to epigenetics and atherosclerosis were found. The major contributing countries were the China (522, 28.23%), United States (485, 26.23%), and Germany (119, 6.44%). The greatest number of retrieved publications were published in the journal, “Arteriosclerosis, Thrombosis, and Vascular Biology” (62, 3.66%). The publication “Oxidative Stress and Diabetic Complications” was cited 2370 times. The most frequent keywords were “DNA methylation” and “LncRNA”. Publications on epigenetic research in the atherosclerosis field have increased significantly every year, indicating that the study of epigenetic modifications plays an increasingly important role in understanding the pathology of atherosclerosis.

DNA methylation "GrimAge" acceleration mediates sex differences in verbal learning and memory: Findings from the health and retirement study

AbstractBackgroundEvidence from cognitive science support sex differences in verbal memory, that tend to favor women. Epigenetic research has also shown slower rates of biological aging in women compared to men. The aim of the current study examined whether sex differences in biological aging mediate sex differences in verbal learning/memory in older adults.MethodData was obtained from the Harmonized Cognitive Assessment Protocol and the 2016 Venous Blood Study, sub‐studies of the 2016 wave of the Health and Retirement Study (HRS). Thirteen epigenetic “clocks” were constructed from these data and made publicly available by HRS staff. DNA methylation “GrimAge” clock was used as the indicator of biological aging, given evidence relating it to cognition in prior studies. A sample of 1,505 participants (mean age =75, SD= 6.8, male= 42%, White= 81%, Black=13%, Hispanic= 6%), with full data were included in the analyses. The residual from age adjusted GrimAge (AgeAccelGrim) was used as the measure of age acceleration. Cognitive composites were constructed from the learning and delayed recall trials of the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task and the Wechsler Memory Scale‐IV, Logical Memory subtest and used as the outcome measures. Mediation analysis tested whether AgeAccelGrim mediated (5,000 resamples) the association between sex and learning/recall composites. Chronological age, years of education, smoking status, white blood cell count, and race/ethnicity were included as covariates.ResultMediation analyses revealed a total direct effect of sex on learning (β=.32, 95% CI [.26, .37]), with a significant indirect effect of AgeAccelGrim, that explained 12.5% of the total effect of sex (CI [.02, .06]). A similar pattern was revealed for delayed recall (total effect of sex β= .26, 95% CI [.20, .32]), with AgeAccelGrim accounting for 11.5% of the total effect (95% CI [.01, .04]).ConclusionWomen performed better on verbal learning/recall measures compared to men, and this association was partially explained by slower biological aging in women. These findings demonstrate the potential for epigenetic markers of aging to increase understanding of sex differences in verbal learning and memory in older adults.

“Passing Down Pollution”: (Inter)generational Toxicology and (Epi)genetic Environmental Health

Concern about the harmful health effects of industrial pollution is increasingly taking on an intergenerational dimension. In environmental health sciences such as toxicology, this has resulted in emphasizing the influence of toxic chemicals, substances, and situations across generations. Toxic relationalities are now being explored through research on gene-environment interaction, including toxicogenomics and epigenetic research through animal experiments and birth cohort studies. Based on fieldwork conducted among reproductive and developmental toxicologists working in Nanjing, China, this article shows how toxicological research both expresses and produces renewed anxieties about "passing down pollution." These toxicological accounts of intergenerational harm problematically work through overly simplistic renderings of reproduction and biological relatedness. But they also have the potential to catalyze creative understandings of toxic relationalities and responsibilities at a moment when making kin is increasingly seen as key to securing livable futures. [toxicology, environment, epigenetics, kinship, China].

The SEQC2 epigenomics quality control (EpiQC) study

BackgroundCytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA’s Epigenomics Quality Control Group.ResultsEach sample is processed in multiple replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), enzymatic deamination method (EMSeq), targeted methylation sequencing (Illumina Methyl Capture EPIC), single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies, and 850k Illumina methylation arrays. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, bwa-meth, and BitMapperBS), we find overall high concordance between assays, but also differences in efficiency of read mapping, CpG capture, coverage, and platform performance, and variable performance across 26 microarray normalization algorithms.ConclusionsThe data provided herein can guide the use of these DNA reference materials in epigenomics research, as well as provide best practices for experimental design in future studies. By leveraging seven human cell lines that are designated as publicly available reference materials, these data can be used as a baseline to advance epigenomics research.

Shared Relations: Trauma and Kinship in the Afterlife of Death.

Since 2013, we have studied the logic and narratives of an environmental epigenetics research team that studies the correlations between early childhood adversity (ECA), specific biomarkers, and suicide risk. Within this research program, kin of the deceased participate in psychological autopsies, which researchers use to establish to classify the deceased within a typology of suicide with or without abuse. We focus on the words of these family respondents and their reflections on the life and death of their loved ones, and life after that death, to consider the slippery, transgressive, and relational character of trauma and its effects. Studies of the residues of past experiences provide crucial insights into the complex, unpredictable, and unsettled nature of kin relations. These relations are based in entwined biographies of the living and the dead and illustrate the holds that people have on each other and destabilize biomedical models of individualized trajectories of suicide risk. [suicide, psychological autopsies, trauma, care, kinship].

Epigenetic modifications in acute myeloid leukemia: The emerging role of circular RNAs (Review).

Canonical epigenetic modifications, which include histone modification, chromatin remodeling and DNA methylation, play key roles in numerous cellular processes. Epigenetics underlies how cells that posses DNA with similar sequences develop into different cell types with different functions in an organism. Earlier epigenetic research has primarily been focused at the chromatin level. However, the number of studies on epigenetic modifications of RNA, such as N1-methyladenosine, 2′-O-ribosemethylation, inosine, 5-methylcytidine, N6-methyladenosine (m6A) and pseudouridine, has seen an increase. Circular RNAs (circRNAs), a type of RNA species that lacks a 5′ cap or 3′ poly(A) tail, are abundantly expressed in acute myeloid leukemia (AML) and may regulate disease progression. circRNAs possess various functions, including microRNA sponging, gene transcription regulation and RNA-binding protein interaction. Furthermore, circRNAs are m6A methylated in other types of cancer, such as colorectal and hypopharyngeal squamous cell cancers. Therefore, the critical roles of circRNA epigenetic modifications, particularly m6A, and their possible involvement in AML are discussed in the present review. Epigenetic modification of circRNAs may become a diagnostic and therapeutic target for AML in the future.

A Biological Caste System? An Investigation of Epigenetics and Socioeconomic Status in Western Society

Epigenetic research has revealed that socioeconomic status (SES) affects people’s lives much more than previously thought. Studies have previously found links between SES and health outcomes that could not be explained by factors classically attributed to the phenomenon of health disparities between the rich and the poor. Further research suggests that epigenetic markers that correlate with SES can have physiologic effects on the individual carrying them, including risk for cardiovascular disease and depression. These markers modulate gene expression without altering the genetic code and are typically regulated by the environment in which an individual or their ancestors lived. Current findings highlight the importance of putting medical care in the context of patient experience, but this research only scratches the surface of the association between SES-related changes in the epigenome and social mobility. Future studies can further investigate if stressors related to low SES are driving epigenetic changes that affect health outcomes. This relationship may have societal consequences and could shape the future of medicine by influencing policy making and personalized patient care.

Insights Into the Role of DNA Methylation in Immune Cell Development and Autoimmune Disease.

To date, nearly 100 autoimmune diseases have been an area of focus, and these diseases bring health challenges to approximately 5% of the population worldwide. As a type of disease caused by tolerance breakdown, both environmental and genetic risk factors contribute to autoimmune disease development. However, in most cases, there are still gaps in our understanding of disease pathogenesis, diagnosis, and treatment. Therefore, more detailed knowledge of disease pathogenesis and potential therapies is indispensable. DNA methylation, which does not affect the DNA sequence, is one of the key epigenetic silencing mechanisms and has been indicated to play a key role in gene expression regulation and to participate in the development of certain autoimmune diseases. Potential epigenetic regulation via DNA methylation has garnered more attention as a disease biomarker in recent years. In this review, we clarify the basic function and distribution of DNA methylation, evaluate its effects on gene expression and discuss related key enzymes. In addition, we summarize recent aberrant DNA methylation modifications identified in the most important cell types related to several autoimmune diseases and then provide potential directions for better diagnosing and monitoring disease progression driven by epigenetic control, which may broaden our understanding and contribute to further epigenetic research in autoimmune diseases.

Strengthening Population Health Perspectives in Physical Therapist Practice Using Epigenetics.

Health starts where we live, learn, work, and play. Population health represents a unifying paradigm for understanding systematic variations in health and related factors, informing integrated action, and reducing health disparities. The pathways connecting social, environmental, and structural factors and various health outcomes have been illuminated by the emergence of epigenetic and epigenomic research, further bolstering the value of population health perspectives in supporting clinical practice, community-based programs, and societal policies. The purpose of this perspective is to consider the placement of epigenetic and epigenomic insights within a population health framework to strengthen the physical therapy profession's understanding of variations in health, inform integrated action, and further justify our role in reducing health-related disparities.

Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology: Unified Evolution Theory.

The current evolutionary biology theory primarily involves genetic alterations and random DNA sequence mutations to generate the phenotypic variation required for Darwinian natural selection to act. This neo-Darwinian evolution is termed the Modern Evolution Synthesis and has been the primary paradigm for nearly 100 years. Although environmental factors have a role in neo-Darwinian natural selection, Modern Evolution Synthesis does not consider environment to impact the basic molecular processes involved in evolution. An Extended Evolutionary Synthesis has recently developed that extends the modern synthesis to consider non-genetic processes. Over the past few decades, environmental epigenetics research has been demonstrated to regulate genetic processes and directly generate phenotypic variation independent of genetic sequence alterations. Therefore, the environment can on a molecular level through non-genetic (i.e. epigenetic) mechanisms directly influence phenotypic variation, genetic variation, inheritance and adaptation. This direct action of the environment to alter phenotype that is heritable is a neo-Lamarckian concept that can facilitate neo-Darwinian (i.e. Modern Synthesis) evolution. The integration of genetics, epigenetics, Darwinian theory, Lamarckian concepts, environment, and epigenetic inheritance provides a paradigm shift in evolution theory. The role of environmental-induced epigenetic transgenerational inheritance in evolution is presented to describe a more unified theory of evolutionary biology.

Genome-wide identification, classification, and expression analysis of the JmjC domain-containing histone demethylase gene family in birch

BackgroundHistone methylation occurs primarily on lysine residues and requires a set of enzymes capable of reading, writing, and erasing to control its establishment and deletion, which is essential for maintaining chromatin structure and gene expression. Histone methylation and demethylation are contributed to plant growth and development, and are involved in adapting to environmental stresses. The JmjC domain-containing proteins are extensively studied for their function in histone lysine demethylation in plants, and play a critical role in sustaining histone methylation homeostasis.ResultsIn this study, a total of 21 JmjC domain-containing histone demethylase proteins (JHDMs) in birch were identified and classified into five subfamilies based on structural characteristics and phylogenetic relationships among Arabidopsis, rice, maize, and birch. Although the BpJMJ genes displayed significant schematic variation, their distribution on the chromosomes is relatively uniform. Additionally, the BpJMJ genes in birch have never experienced a tandem-duplication event proved by WGD analysis and were remaining underwent purifying selection (Ka/Ks < < 1). A typical JmjC domain was found in all BpJMJ genes, some of which have other essential domains for their functions. In the promoter regions of BpJMJ genes, cis-acting elements associated with hormone and abiotic stress responses were overrepresented. Under abiotic stresses, the transcriptome profile reveals two contrasting expression patterns within 21 BpJMJ genes. Furthermore, it was established that most BpJMJ genes had higher expression in young tissues under normal conditions, with BpJMJ06/16 having the highest expression in germinating seeds and participating in the regulation of BpGA3ox1/2 gene expression. Eventually, BpJMJ genes were found to directly interact with genes involved in the “intracellular membrane” in respond to cold stress.ConclusionsThe present study will provide a foundation for future experiments on histone demethylases in birch and a theoretical basis for epigenetic research on growth and development in response to abiotic stresses.

Epigenetic studies in suicidal ideation and behavior.

Most psychiatric disorders are associated with an elevated risk of suicide. Suicidal behavior is the product of the interaction of many risk factors, such as genetics and environmental factors. Hence, epigenetics research may help to understand the mechanisms leading to suicidal ideation and behavior. This review will discuss epigenetic studies in both suicidal ideation and behavior. Epigenetic modifications are likely to be important in both suicidal ideation and behavior. Most of the reviewed studies found significant epigenetic modifications linked with suicidal behavior rather than ideation. Although sizable research has been carried out on this topic, most studies have been done on small-scale samples, and future research is required in larger samples with better clinical characterization of suicide phenotypes to investigate these epigenetic modifications further.

A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies.

Depression is an umbrella term used to describe a mood disorder with a broad spectrum of symptoms including a persistent feeling of sadness, loss of interest, and deficits in social behavior. Epigenetic research bridges the environmental and genetic landscape and has the potential to exponentially improve our understanding of such a complex disorder. Depression is also a sexually dimorphic disorder and variations exist within epigenetic modification sites between sexes. These sex-specific mediators may impact behavioral symptomology and could serve as therapeutic targets for treatments to improve behavioral deficits. This mini review will focus on the social behavior perspective of depression and specifically explore the sexually different epigenetic modifications on depression.

Clinical Genealogical and Epigenetic Examination of Patients with Juvenile Epiphysiolysis of the Femoral Head

Summary. Slipped capital femoral epiphysis (SCFE) is a multifactorial disease caused by a number of factors, and each of them can be triggered in its occurrence. Modern research is increasingly pointing to the leading role of epigenetic structures in the origin and course of this group of diseases. In recent years, the most promising area is the study of the role of microRNAs as an epigenetic factor that plays a leading role in the pathogenesis of multifactorial diseases.&#x0D; Objective: to develop a methodology for genetic genealogical examination of patients with juvenile epiphysiolysis of the femoral head.&#x0D; Materials and Methods. The study material was 26 patients with SCFE (15 girls and 11 boys) in different periods of sexual development: prepuberty – 7 patients, induction of puberty – 12 patients, and puberty and postpuberty – 7 patients. A questionnaire developed by us was used for clinical and genealogical research of the patients. The material for the epigenetic study, namely the study of microRNA-21 expression in patients with SCFE, was venous blood.&#x0D; Results. The expression of microRNA-21 in the blood of patients with SCFE is different (average expression is 0.86 conventional units) from those of healthy donors (average 0.393 conventional units) of the same age (p&lt;0.05). Analysis of dependence on the period of sexual development revealed statistical differences in indicators depending on the group (p&lt;0.05). No dependence of the level of microRNA-21 expression in patients with SCFE on sex and the period before or after surgery (p&gt;0.05) was revealed. The obtained data on the probability of the influence of hereditary factors on the occurrence of SCFE are statistically significant (p&lt;0.05).&#x0D; Conclusions. Our results of epigenetic and clinical genealogical research of patients with SCFE showed a high probability of influence of hereditary and epigenetic factors on the occurrence and course of this disease.

Revealing the biological basis of mental illness: epigenetic research as a new direction in diagnosis and treatment

Summary. Mental disorders are clinically heterogeneous chronic diseases resulting from complex interactions between genotype variants and environmental factors. Epigenetic processes, such as DNA methylation and post-translational histone modification, determine the interpretation by the body at the cellular and tissue levels of various environmental factors. Given that epigenetic modifications are environmentally sensitive, stable and reversible, epigenetic research in psychiatry may be a promising approach to better understanding and treating mental illness. This review discusses the clinical opportunities and challenges posed by epigenetic research in psychiatry. Using individual examples, the main conclusions are drawn that confirm the role of adverse life events, alone or in combination with genetic risk, in the epigenetic programming of neuropsychiatric systems. Further epigenetic studies show encouraging results in the use of methylation changes as diagnostic markers of disease manifestations and provide predictive tools for assessing progression and response to treatment. The potential for the use of targeted epigenetic pharmacotherapy, combined with psychosocial methods, in the context of the personalized medicine of the future in psychiatry is discussed next. It concludes with a discussion of methodological limitations that can make it difficult to interpret epigenetic data in psychiatry. They mainly arise due to the heterogeneity of individuals, both at the level of the whole organism and at the level of tissues, and require new strategies to better assess the biological significance of epigenetic data and their translational use in psychiatry. Overall, we believe that epigenetics can provide new insights and a more comprehensive understanding of the etiology and pathogenesis of mental illness, and should ultimately improve the nosology, treatment and prevention of mental disorders.

Small RNAs Worm Up Transgenerational Epigenetics Research.

DNA is central to the propagation and evolution of most living organisms due to the essential process of its self-replication. Yet it also encodes factors that permit epigenetic (not included in DNA sequence) flow of information from parents to their offspring and beyond. The known mechanisms of epigenetic inheritance include chemical modifications of DNA and chromatin, as well as regulatory RNAs. All these factors can modulate gene expression programs in the ensuing generations. The nematode Caenorhabditis elegans is recognized as a pioneer organism in transgenerational epigenetic inheritance research. Recent advances in C. elegans epigenetics include the discoveries of control mechanisms that limit the duration of RNA-based epigenetic inheritance, periodic DNA motifs that counteract epigenetic silencing establishment, new mechanistic insights into epigenetic inheritance carried by sperm, and the tantalizing examples of inheritance of sensory experiences. This review aims to highlight new findings in epigenetics research in C. elegans with the main focus on transgenerational epigenetic phenomena dependent on small RNAs.

Role of Epigenetics in the Pathogenesis, Treatment, Prediction, and Cellular Transformation of Asthma.

Asthma is a mysterious disease with heterogeneity in etiology, pathogenesis, and clinical phenotypes. Although ongoing studies have provided a better understanding of asthma, its natural history, progression, pathogenesis, diversified phenotypes, and even the exact epigenetic linkage between childhood asthma and adult-onset/old age asthma remain elusive in many aspects. Asthma heritability has been established through genetic studies, but genetics is not the only influencing factor in asthma. The increasing incidence and some unsolved queries suggest that there may be other elements related to asthma heredity. Epigenetic mechanisms link genetic and environmental factors with developmental trajectories in asthma. This review provides an overview of asthma epigenetics and its components, including several epigenetic studies on asthma, and discusses the epigenetic linkage between childhood asthma and adult-onset/old age asthma. Studies involving asthma epigenetics present valuable novel approaches to solve issues related to asthma. Asthma epigenetic research guides us towards gene therapy and personalized T cell therapy, directs the discovery of new therapeutic agents, predicts long-term outcomes in severe cases, and is also involved in the cellular transformation of childhood asthma to adult-onset/old age asthma.

Epidemiologists’ ambivalence towards the epigenetics of social adversity

This article studies how social epidemiologists get involved in research carried out on rodent models to explore the biological pathways underpinning exposure to social adversity in early life. We analyze their interdisciplinary exchanges with biologists in a social epigenetics project—i.e., in the experimental study of molecular alterations following social exposures. We argue that social epidemiologists are ambivalent regarding the use of non-human animal models on two levels: first, in terms of whether such models provide scientific evidence useful to social epidemiology, and second, regarding whether such models help promote their conception of public health. While they maintain expectations towards rodent experiments by elevating their functional value over their representational potential, they fear that their research will contribute to a public health approach that focuses on individual responsibility rather than the social causes of health inequalities. This interdisciplinary project demonstrates the difficulties encountered when research in social epigenetics engages with the complexities of laboratory experiments and social environments, as well as the conflicting sociopolitical projects stemming from such research.