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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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310 hot topic(s) found with the query "Epigenetics"

Pregnancy advances your 'biological' age - but giving birth turns it back.
Saima Sidik et al. Nature 2024 3 (Posted: Mar 25, 2024 9AM)

From the article: " DNA-methylation patterns can be used to estimate a person’s ‘biological age’, which reflects the physiological stresses that a person’s body has accrued over time. Some research has found that biological age is a better predictor of health problems such as cardiovascular disease3 and dementia4 than a person’s chronological age. Pregnancy may lead to changes in the distribution of certain chemical markers on a pregnant person’s DNA — changes similar to those that are a hallmark of getting older. But new research shows that, several months after a person gives birth, the chemical patterns revert to an earlier state. The results strengthen previous preliminary results in humans. "

Health-Related quality of life and DNA Methylation-Based aging biomarkers among survivors of childhood cancer.
Noel-Marie Plonski et al. J Natl Cancer Inst 2024 3 (Posted: Mar 07, 2024 8AM)

From the abstract: "Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related-quality-of-life (HRQOL). However, associations between DNA methylation (DNAm)-based aging biomarkers and HRQOL have not been evaluated. DNAm was generated with Infinium EPIC BeadChip on blood-derived DNA (median[range] for age at blood draw?=?34.5[18.5-66.6] years) and HRQOL was assessed with age at survey (32.3[18.4-64.5] years) from 2,206 survivors in the St Jude Lifetime Cohort. "

Epigenome-wide association studies of prenatal maternal mental health and infant epigenetic profiles: a systematic review.
Emily Drzymalla et al. Transl Psychiatry 2023 12 (1) 377 (Posted: Dec 08, 2023 8AM)

From the abstract: "Prenatal stress and poor maternal mental health are associated with adverse offspring outcomes; however, the biological mechanisms are unknown. Epigenetic modification has linked maternal health with offspring development. Epigenome-wide association studies (EWAS) have examined offspring DNA methylation profiles for association with prenatal maternal mental health to elucidate mechanisms of these complex relationships. The objective of this study is to provide a comprehensive, systematic review of EWASs of infant epigenetic profiles and prenatal maternal anxiety, depression, or depression treatment. "

Neighborhood Deprivation Measures and DNA Methylation Clocks-Understanding the Real Needs of Each Person.
Benjamin D Horne et al. JAMA Netw Open 2023 11 (11) e2344688 (Posted: Dec 02, 2023 9AM)

From the article: " A recent study reports a unique and powerful approach for finding neighborhood factors marking risks of early death and disease.4 Measurement of racial segregation using spatial clustering methods and separating that from economic deprivation (and education) aid in clarifying the sources of health concerns. The study uses methylation patterns which can be remodeled by many factors such as smoking, physical activity, diet, infection, and stressors from the childhood environment (eg, lack of loving adult support, malnutrition), adverse living conditions (eg, noise pollution, particulate matter air pollution), and poor interactions with others (eg, emotional or physical abuse). "

Navigating epigenetic epidemiology publications
W Yu et al, BMC Epig Comm, November 22, 2023, (Posted: Nov 27, 2023 11AM)

From the abstract: "Since its beginning more than 75 years ago, epigenetics has been an evolving field with growing applications to the study of cancer, aging, and gene expression in response to environmental exposures. The emergence of high-throughput technology for measuring epigenetic markers has enabled population-based studies. The relatively new field of epigenetic epidemiology investigates epigenetic associations from a population perspective for insights into disease risk, prevention, and progression. "

Epigenetics of Early-Life Socioeconomic Stressors and the Impact on Childhood Body Mass Index—Potential Mechanism and Biomarker?
UP Gujral et al, JAMA Pediatrics, September 5, 2023 (Posted: Sep 05, 2023 1PM)

From the paper: "a recent study indicates that salivary epigenetics, an easy measure to obtain in field or clinic, can be used to further explore the questions of pediatric obesity and related outcomes. Epigenetic and physiological BMI may be present at birth and remain stable throughout childhood and adolescence. These findings also add further evidence to a critical window, that of early life, at which to intervene to prevent childhood and adolescent obesity."

Salivary Epigenetic Measures of Body Mass Index and Social Determinants of Health Across Childhood and Adolescence
L Raffington et al, JAMA Pediatrics, September 5, 2023 (Posted: Sep 05, 2023 1PM)

From the abstract: "Can the long arm of childhood on aging-related health be measured in real time? In this study that analyzed data from 2 US cohort studies, epigenetic measures of body mass index developed in adults were valid biomarkers of children’s body mass index and were associated with socioeconomic and racialized inequalities experienced in childhood, especially at birth. These findings are in line with the hypothesis that early-life conditions are especially important factors in epigenetic regulation of later-life health."

Early-Life Adversity Associations With Later Life Epigenetic Aging Profiles in the Multi-Ethnic Study of Atherosclerosis.
Lauren L Schmitz et al. Am J Epidemiol 2023 8 (Posted: Aug 15, 2023 2PM)

This study leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA) on experiences of threat and deprivation in participants’ early lives (i.e., before the age of 18) to examine whether exposure to specific dimensions of early life adversity are associated with epigenetic profiles at older ages that are indicative of accelerated biological aging. The sample included 842 respondents in MESA with DNA methylation data collected between 2010-2012 who answered questions on early life adversities in a 2018-2019 phone follow-up. We find experiences of deprivation, but not threat, are associated with later-life GrimAge epigenetic aging signatures that were developed to predict mortality risk.

Predictive evidence of the relevance of epigenetics to PTSD.
Leon Mutesa et al. Nat Rev Genet 2023 8 (Posted: Aug 09, 2023 4PM)

Post-traumatic stress disorder (PTSD) is a complex mental health condition that can occur after a life-threatening or otherwise traumatic event. Although its molecular causes are unclear, its development is thought to involve a range of biological, psychological and environmental factors. In 2009, Yehuda and Bierer posited that epigenetic modifications, such as DNA methylation, may occur in response to environmental influences such as trauma exposure, thus altering the functional expression of genes. These mechanisms may explain the intergenerational transmission of PTSD across affected families.

Epigenetic alterations in response to toxic exposures - the need to determine effect modification by nutrient status.
Krista S Crider et al. J Nutr 2023 6 (Posted: Jun 15, 2023 8AM)

The challenge and promise of utilizing epigenetic and biomarker data to explore the impact of prenatal exposures on offspring health are highlighted in a recent publication. Epigenetic data can be particularly difficult to analyze and interpret in nutritional and environmental epidemiological studies. Best practices in analyzing epigenetic data are evolving.

Refining epigenetic prediction of chronological and biological age
E Bernabeau et al, Genome Medicine, February 28, 2023 (Posted: Mar 01, 2023 0PM)

Epigenetic clocks can track both chronological age (cAge) and biological age (bAge). The latter is typically defined by physiological biomarkers and risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates of cAge and bAge become more precise. Here, we aim to develop accurate epigenetic predictors of cAge and bAge, while improving our understanding of their epigenomic architecture.

Analysis of Pregnancy Complications and Epigenetic Gestational Age of Newborns
CL Acosta et al, JAMA Network Open, February 24, 2023 (Posted: Feb 24, 2023 11AM)

Is exposure to gestational diabetes, gestational hypertension, or preeclampsia associated with biological gestational age, measured via epigenetic clocks, in newborns? In this national multisite cohort study of 1801 children, preeclampsia and gestational diabetes were significantly associated with decelerated gestational age in exposed offspring at birth vs unexposed offspring (ie, they were estimated to be biologically younger than their chronological gestational age), and these associations were more pronounced in female offspring. No associations were observed for gestational hypertension and accelerated or decelerated biological age.

Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial
R Waziry et al, Nature Aging, February 9, 2023 (Posted: Feb 13, 2023 10AM)

Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n?=?220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2?yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health.

Simultaneous sequencing of genetic and epigenetic bases in DNA.
Jens Füllgrabe et al. Nature biotechnology 2023 2 (Posted: Feb 08, 2023 0PM)

Use of incorrect and correct methods to account for age in studies on epigenetic accelerated aging: implications and recommendations for best practices.
Nancy Krieger et al. American journal of epidemiology 2023 2 (Posted: Feb 05, 2023 11AM)

Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic “clocks” (which estimate age via DNA methylation patterns (DNAm)), we report on three different approaches – 1 incorrect and 2 correct – in the epidemiologic literature on treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption).

Epigenetic profile of Japanese supercentenarians: a cross-sectional study
S Komaki et al, The Lancet Healthy Longevity, February 2023 (Posted: Feb 03, 2023 7AM)

Epigenome-wide association analyses showed that centenarians and supercentenarians had younger-than-expected epigenetic states (DNA methylation profiles similar to those of non-centenarians) for 557 CpG sites enriched in cancer-related and neuropsychiatric-related genes, whereas these individuals had advanced (or older) epigenetic states for 163 CpG sites represented by genes related to TGF-ß signalling, which is involved in anti-inflammatory responses and known to contribute to healthy ageing.

Molecular mechanisms of environmental exposures and human disease
H Wu et al, Nature Rev Genetics, January 30, 2023 (Posted: Jan 31, 2023 8AM)

We review evidence showing the environmental impact on gene expression through epigenetic modifications, including DNA methylation, histone modification and non-coding RNAs. We also highlight recent studies that evaluate recently discovered molecular processes through which the environment can exert its effects, including extracellular vesicles, the epitranscriptome and the mitochondrial genome. Finally, we discuss current challenges when studying the exposome — the cumulative measure of environmental influences over the lifespan — and its integration into future environmental health research.

Mapping the minutiae of the human methylome.
Minton Kirsty et al. Nature reviews. Genetics 2023 1 1 (Posted: Jan 18, 2023 1PM)

Knowing the DNA methylation status of a cell is crucial to understanding its gene expression pattern and hence phenotype. However, most available datasets of human DNA methylation cover only a small fraction of the 30 million methylation sites in the human genome and are limited to in vitro-cultured cells or bulk tissues containing undefined mixtures of cells. A publicly available comprehensive atlas of the human methylome, together with cell type-specific markers and computational tools for the analysis of mixed samples, provides a wealth of data for further discovery.

A DNA methylation atlas of normal human cell types
N Loyfer et al, Nature, January 4, 2023 (Posted: Jan 05, 2023 5AM)

We describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39?cell types sorted from 205?healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development.

Towards a unification of the 2 meanings of "epigenetics".
Huang Sui et al. PLoS biology 2022 12 (12) e3001944 (Posted: Jan 05, 2023 5AM)

The notion of epigenetic “marks” used by molecular biologists is conceptually disconnected from the idea of Waddington’s epigenetic “landscape” that is used by systems biologists and biophysicists. Recent advances suggest that these 2 distinct schools of thought could be united.

DNA methylation provides molecular links underlying complex traits
Nature Genetics, January 2, 2023 (Posted: Jan 02, 2023 0PM)

We profiled human DNA methylation for 987 GTEx samples across nine tissues and characterized how genetic regulation of the methylome, compared with the transcriptome, contributes to GWAS phenotypes. This resource contributes to our understanding of molecular regulatory mechanisms in human tissues and their effects on complex traits.

Epigenetic clocks, aging, and cancer.
Johnstone Sarah E et al. Science (New York, N.Y.) 2022 12 (6626) 1276-1277 (Posted: Dec 26, 2022 11AM)

Cancer and aging are accompanied by stereotyped changes to the epigenetic landscape, including progressive loss of DNA methylation over gene-poor genomic regions. Global hypomethylation arises in cells that have undergone many divisions, likely owing to imperfect maintenance. Evidence suggests that global hypomethylation represents a “mitotic clock” that counts divisions in somatic cells and functions to restrain aging cells and limit malignant progression. Therapies that modulate the pace of methylation loss or eliminate hypomethylated cells could alleviate aging associated diseases or cancers.

The Use of Cell-free DNA in Clinical Practice: Work in Progress
M Clyne et al, CDC Blog Post, December 14, 2022 Brand (Posted: Dec 14, 2022 5PM)

Since its discovery in 1948, the utility of cfDNA has been studied extensively in screening, diagnosis, prognosis, therapy and monitoring disease progression. Although effort has focused on cancer, and mostly in NSCLC, other areas of research are ongoing, including autoimmune disease, metabolic disorders, Alzheimer’s disease, and other neurologic conditions, COVID-19, myocarditis and dilated cardiomyopathy, and refractory epilepsy. In addition to circulating cfDNA, potential clinical applications exist for other omics, including epigenetics and exosomal miRNAs, as well as use of cfDNA in other body fluids (e.g. urine).

What's my age again?
Marioni Riccardo E et al. Nature reviews. Genetics 2022 12 (Posted: Dec 09, 2022 6AM)

Age is a major (and sometimes the major) risk factor for many diseases. We all age at the same chronological rate but there is huge variation in what diseases we get and when we get them. Two people of the same chronological age can have very different risk profiles but is there a way to quantify our rate of biological ageing, and do different organs and tissues age at different rates?

DNA Methylation Implicated in Human Obesity and Diabetes
ME Tucker, Medscape, November 2022 (Posted: Nov 14, 2022 6AM)

Previous attempts to identify causal associations between DNA methylation and both obesity and type 2 diabetes have been hindered by challenges in collecting and isolating cells from human tissue. Recent data suggest that manipulation of DNA methylation enzymes in adipocytes can induce or prevent obesity and type 2 diabetes through cellular effects on energy expenditure and insulin sensitivity.

Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics.
Migliore Lucia et al. Nature reviews. Neurology 2022 9 (11) 643-660 (Posted: Nov 06, 2022 1PM)

With the exception of a few monogenic forms, Alzheimer disease (AD) has a complex aetiology that is likely to involve multiple susceptibility genes and environmental factors. The role of environmental factors is difficult to determine and, until a few years ago, the molecular mechanisms underlying gene–environment (G?×?E) interactions in AD were largely unknown. Here, we review evidence that has emerged over the past two decades to explain how environmental factors, such as diet, lifestyle, alcohol, smoking and pollutants, might interact with the human genome. In particular, we discuss how various environmental AD risk factors can induce epigenetic modifications of key AD-related genes and pathways.

From Polygenic Risk Scores to Methylation Risk Scores: What are the Clinical Applications?
E Drzymala et al, CDC Blog Post, October 7, 2022 Brand (Posted: Oct 07, 2022 11AM)

Better understanding of a person’s risk for disease is important for prevention and treatment. Considering a person’s unique set of environmental and genetic risk factors is crucial for this understanding. Methylation risk scores (MRS) are in a unique position to combine these genetic and environmental factors over time. More research will be needed to assess the validity and utility of MRS for risk prediction alongside genetic and environmental models.

Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults.
Li Xiangwei et al. Nature communications 2022 9 (1) 5269 (Posted: Sep 08, 2022 7AM)

DNA methylation (DNAm) patterns in peripheral blood have been shown to be associated with aging related health outcomes. We perform an epigenome-wide screening to identify CpGs related to frailty, defined by a frailty index (FI), in a large population-based cohort of older adults from Germany, the ESTHER study. Sixty-five CpGs are identified as frailty related methylation loci.

Communicating Precision Medicine Research: Multidisciplinary Teams and Diverse Communities.
Beans Julie A et al. Public health genomics 2022 8 1-9 (Posted: Sep 01, 2022 3PM)

A shared definition of precision medicine research as well as six case examples of precision medicine research involving genetic risk, pharmacogenetics, epigenetics, the microbiome, mobile health, and electronic health records were developed. Discussion/Conclusion: The precision medicine research definition and case examples can be used as planning tools to establish a shared understanding of the scope of precision medicine research across multidisciplinary teams and with the diverse communities.

Methylation risk scores are associated with a collection of phenotypes within electronic health record systems
M Thompson et al, NPJ Genomic Medicine, August 26, 2022 (Posted: Aug 26, 2022 8AM)

We considered the epigenetic analog of PRS, methylation risk scores (MRS), a linear combination of methylation states. We measured methylation across a large cohort (n?=?831) of diverse samples in the UCLA Health biobank, for which both genetic and complete EHR data are available. We constructed MRS for 607 phenotypes spanning diagnoses, clinical lab tests, and medication prescriptions. When added to a baseline set of predictive features, MRS significantly improved the imputation of 139 outcomes, whereas the PRS improved only 22 (median improvement for methylation 10.74%, 141.52%, and 15.46% in medications, labs, and diagnosis codes, respectively, whereas genotypes only improved the labs at a median increase of 18.42%).

Analysis of Epigenetic Age Acceleration and Healthy Longevity Among Older US Women
P Jain et al, JAMA Network Open, July 27, 2022 (Posted: Jul 27, 2022 3PM)

This cohort study was a secondary analysis of 3 Women’s Health Initiative ancillary studies among 1813 women eligible to survive to age 90 years by end of study period. The study found that increased epigenetic age acceleration as measured by 4 epigenetic clocks was associated with lower odds of survival to age 90 years with intact mobility; results were similar when including intact cognitive functioning. Meaning These findings suggest that epigenetic age acceleration may be a useful biomarker to estimate functional and cognitive aging among older women.

Peripheral blood DNA methylation profiles predict future development of B-cell Non-Hodgkin Lymphoma
AE Perez et al, NPJ Precision Oncology, July 21, 2022 (Posted: Jul 22, 2022 8AM)

Fulfilling the Promise of Epigenetics Requires More Studies in Diverse Populations
E Drzymalla et al, CDC Blog Post, July 18, 2022 Brand (Posted: Jul 18, 2022 10AM)

While much has been said about the importance of diversity in genomics research, we are only beginning to realize the importance of diversity in epigenetics. More epigenetic research needs to be undertaken in diverse populations with different genetic and environmental factors. This will go a long way towards fulfilling the promise of epigenetics as a tool for health equity science.

Diversity in EWAS: current state, challenges, and solutions
CE Breeze et al, Genome Medicine, July 6, 2022 (Posted: Jul 06, 2022 6AM)

Here, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include fostering community involvement, new data generation, and cost-effective approaches such as locus-specific analysis and ancestry variable region analysis.

Linking genetic variants to kidney disease via the epigenome
Nature Genetics, June 23, 2022 (Posted: Jun 25, 2022 11AM)

The largest GWAS for kidney function so far provided the starting point for integrated multi-stage annotation of genetic loci. Whole kidney and single-cell epigenomic information is crucial for translating GWAS information to the identification of causal genes and pathogenetic (and potentially targetable) cellular and molecular mechanisms of kidney disease.

The missing diversity in human epigenomic studies
CE Breeze, Nature Genetics, June 9, 2022 (Posted: Jun 10, 2022 7AM)

Recent work has highlighted a lack of diversity in genomic studies. However, less attention has been given to epigenomics. Here, we show that epigenomic studies are lacking in diversity and propose several solutions to address this problem. Current efforts to increase representation in genomic research in diverse populations should be paired with similar efforts in epigenomics, which have, thus far, received less attention and scientific scrutiny. Adding ancestry information, which could be inferred from sequencing or genotype array data, to existing epigenomic data could be beneficial in helping researchers understand the potential limitations for annotating and interpreting GWAS loci from different populations.

Making sense of the ageing methylome.
Seale Kirsten et al. Nature reviews. Genetics 2022 5 (Posted: May 08, 2022 7AM)

Over time, the human DNA methylation landscape accrues substantial damage, which has been associated with a broad range of age-related diseases, including cardiovascular disease and cancer. Various age-related DNA methylation changes have been described, including at the level of individual CpGs, such as differential and variable methylation, and at the level of the whole methylome, including entropy and correlation networks. Here, we review these changes in the ageing methylome as well as the statistical tools that can be used to quantify them. We detail the evidence linking DNA methylation to ageing phenotypes and the longevity strategies aimed at altering both DNA methylation patterns and machinery to extend healthspan and lifespan. Lastly, we discuss theories on the mechanistic causes of epigenetic ageing.

DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
M Wielscher et al, Nature Comms, May 3, 2022 (Posted: May 03, 2022 8AM)

Repeat measures of DNA methylation in an inception cohort of firefighters.
Goodrich Jaclyn M et al. Occupational and environmental medicine 2022 3 (Posted: Apr 07, 2022 2PM)

Firefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism linking occupational hazards to adverse health outcomes. We hypothesized that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs).

Exploring the epigenetics of resilience
R Dajani, Nature Genetics, April 4, 2022 (Posted: Apr 04, 2022 2PM)

To do good science, we need to include diverse perspectives, work across disciplines and think outside the box while reminding ourselves that our goal as scientists is to serve humanity. I am sharing my story to encourage others to trust their gut feelings and to have the courage to see what everyone sees, but think what no one has thought.

Grandmaternal smoking during pregnancy is associated with differential DNA methylation in peripheral blood of their grandchildren
SM Watkins et al, EJHG, March 28, 2022 (Posted: Mar 29, 2022 7AM)

We show for the first time that DNAm at a small number of loci in cord blood is associated with grandmaternal smoking in humans. In adolescents we see suggestive associations in regions of the genome which we hypothesised a priori could be involved in transgenerational transmission - we observe sex-specific associations at two sites on the X chromosome and one in an imprinting control region. All are within transcription factor binding sites (TFBSs), and we observe enrichment for TFBS among the CpG sites with the strongest associations.

Genome-wide association studies identify novel genetic loci for epigenetic age acceleration among survivors of childhood cancer
Q Dong et al, Genome Medicine, March 22, 2022 (Posted: Mar 23, 2022 8AM)

Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. We identified novel genetic variants in the SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer.

DNA methylation-based predictors of health: applications and statistical considerations
PD Yousefi et al, Nat Rev Genetics, March 18, 2022 (Posted: Mar 21, 2022 8AM)

DNA methylation data have become a valuable source of information for biomarker development, because, unlike static genetic risk estimates, DNA methylation varies dynamically in relation to diverse exogenous and endogenous factors, including environmental risk factors and complex disease pathology. Reliable methods for genome-wide measurement at scale have led to the proliferation of epigenome-wide association studies and subsequently to the development of DNA methylation-based predictors across a wide range of health-related applications.

Epigenetics: An Emerging Tool for Health Equity Science
E Drzymalla et al, CDC Blog Post, March 8, 2022 Brand (Posted: Mar 08, 2022 10AM)

The biological connections between SDOH and adverse health outcomes are not fully understood. Could the field of epigenetics help us gain better insight into these connections? Epigenetics involves biological processes such as DNA methylation or histone modification that do not change the genome sequence but alter gene expression. Epigenetic markers have been shown to be affected by natural, built, and social environmental exposures such as nutrition, stress, and air pollution. Epigenetic markers may shed light on potential causal links between SDOH and adverse health outcomes and are potentially modifiable, providing new approaches to therapeutics (e.g., cancer).

Racial Disparities in Ion Channelopathies and Inherited Cardiovascular Diseases Associated With Sudden Cardiac Death
M Chahine et al, May 2022 (Posted: Mar 06, 2022 7AM)

Cardiovascular disease (CVD) continues to be the most common cause of death worldwide, and cardiac arrhythmias account for approximately one half of these deaths. The morbidity and mortality from CVD have been reduced significantly over the past few decades; however, disparities in racial or ethnic populations still exist. This review is based on available literature to date and focuses on known cardiac channelopathies and other inherited disorders associated with sudden cardiac death in African American/Black subjects and the role of epigenetics in phenotypic manifestations of CVD, and illustrates existing disparities in treatment and outcomes. The review also highlights the knowledge gaps that limit understanding of the manifestation of phenotypic abnormalities across racial or ethnic groups and discusses disparities associated with device underuse in the management of patients at risk for sudden cardiac death.

Association between maternal depression during pregnancy and newborn DNA methylation
E Drzymalla et al, Trans Psychiatry, November 9, 2021 (Posted: Nov 10, 2021 9AM)

Special focus issue on epigenomics and health disparities: foreword.
Argentieri M Austin et al. Epigenomics 2021 10 (Posted: Oct 15, 2021 10AM)

Although epigenomic researchers have been investigating the influences of physical environmental exposures (e.g., air pollution, contaminants and heavy metal exposures and lifestyle factors such as smoking, alcohol and nutrition) on epigenetic mechanisms for years under the banner of ‘environmental epigenomics’, the field is at a crossroads where a fundamental rethinking of what constitutes a human environment is necessary, especially in the pursuit of understanding disparities in health and disease. It will be crucial for the field of environmental epigenomics to expand its inquiry to the entire exposome (i.e., all nongenetic influences on health, including social, economic, cultural, built environment and housing and psychosocial dimensions of life) in order to truly come to terms with the determinants of health inequality from an epigenomic perspective.

Epigenomic contributions to tumor cell heterogeneity and plasticity
R Mathur et al, Nature Genetics, October 4, 2021 (Posted: Oct 06, 2021 7AM)

Heterogeneity in brain tumors has been viewed through many lenses—from microscopes and experimental models to ‘omic’ analysis at the tissue and single-cell levels. Two studies now characterize patterns of DNA methylation and gene expression in single cells to reveal epigenomic underpinnings of cellular heterogeneity and plasticity in exquisite detail, including mechanistic insight into cellular transitions between stem-like and differentiated-like states.

Impact of paternal education on epigenetic ageing in adolescence and mid-adulthood: a multi-cohort study in the USA and Mexico.
Joyce Brian T et al. International journal of epidemiology 2021 9 (Posted: Sep 19, 2021 10AM)

Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)—the discrepancy between chronological and epigenetic ages.We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. Our findings suggest that EAA captures epigenetic impacts of paternal education independently of personal SES later in life.

Blood DNA Methylation and Incident Coronary Heart Disease Evidence From the Strong Heart Study
AN Acien et al JAMA Cardiology, August 4, 2021 (Posted: Aug 04, 2021 11AM)

In this multi-cohort study, a high-dimensional multi-adjusted model assessing blood DNAm in 2321 American Indian adults selected 505 differentially methylated positions (DMPs) associated with incident CHD in the Strong Heart Study. These DMPs were evaluated in the Women’s Health Initiative, the Framingham Heart Study, and the Atherosclerosis Risk in Communities Study, and several DMPs common across cohorts tagged genes with established associations with cardiovascular disease.

Anatomy of DNA methylation signatures: Emerging insights and applications
EC Diehl et al, AJHG, July 22, 2021 (Posted: Jul 23, 2021 7AM)

DNA methylation (DNAm) signatures are unique patterns of DNAm alterations defined for rare disorders caused by pathogenic variants in epigenetic regulatory genes. The potential of DNAm signatures (also known as “episignatures”) is just beginning to emerge as there are >300 known epigenetic regulatory genes, ~100 of which are linked to neurodevelopmental disorders. To date, approximately 50 signatures have been identified, which have proven unexpectedly successful as predictive tools for classifying variants of uncertain significance as pathogenic or benign.

Socioeconomic changes predict genome-wide DNA methylation in childhood
J Liu et al, MEDRXIV, June 29, 2021 (Posted: Jun 30, 2021 7AM)

Epigenetic clock: a promising mirror of aging
Z Liu et al, Lancet Healthy Longevity, May 2021 (Posted: May 19, 2021 8AM)

We are witnessing rapid progress in the intersection of aging and epigenetics. With advances in this field, we believe that epigenetic clocks could help answer the ultimate question—what is aging and how does it contribute to disease progression across different populations?

Epigenetic-age acceleration in the emerging burden of cardiometabolic diseases among migrant and non-migrant African populations: a population-based cross-sectional RODAM substudy
FP Chilunga et al, Lancet Healthy Longevity, ay 2021 (Posted: May 19, 2021 8AM)

Clinical epigenomics for cardiovascular disease: Diagnostics and therapies.
Fischer Matthew A et al. Journal of molecular and cellular cardiology 2021 Feb (Posted: Feb 12, 2021 11AM)

As an integrator of genetic and environmental inputs, and because of advances in measurement techniques that are highly reproducible and provide sequence information, the epigenome is a rich source of potential biosignatures of cardiovascular health and disease.

Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation
D Mancarella et al, Genome Medicine, February 10, 2021 (Posted: Feb 11, 2021 7AM)

We highlight the importance and define challenges of proper control tissues and cell populations to exploit cancer epigenomes. We summarize recent advances describing mechanisms leading to epigenetic changes in tumorigenesis and briefly discuss advances in investigating their translational potential.

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift
C Panisi et al, JPM, January 2021 (Posted: Jan 26, 2021 8AM)

The epidemiological and clinical findings in autism spectrum disorder cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole.

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR
AK Smith et al, Nature Comm, November 2020 (Posted: Nov 25, 2020 9AM)

Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls.

Association of Neighborhood Deprivation With Epigenetic Aging Using 4 Clock Metrics
KG Lawrence et al, JAMA Network Open, November 4, 2020 (Posted: Nov 05, 2020 6AM)

This cross-sectional study comprised 2630 women who had a sister with breast cancer but had not had breast cancer themselves. Those living in areas with the greatest compared with least neighborhood deprivation had higher epigenetic age acceleration estimated by Hannum, PhenoAge, and GrimAge clocks.

The immune roadmap for understanding multi-system inflammatory syndrome in children: opportunities and challenges
OM Martinez et al, Nature Medicine, November 2, 2020 (Posted: Nov 03, 2020 8AM)

In June 2020, the US National Institutes of Health convened a workshop of immunologists and clinicians to discuss emerging knowledge and identify key questions surrounding MIS-C, with a focus on innate and adaptive immunity, genetics and epigenetics. This Meeting Report describes the main findings from the workshop.

Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes.
García-Calzón Sonia et al. Science translational medicine 2020 Sep (561) (Posted: Sep 19, 2020 8PM)

This study analyzed genome-wide DNA methylation in the blood of drug-naïve patients who were recently diagnosed with T2D. They found that DNA methylation at specific loci associated with future metformin response or tolerance, respectively, across multiple cohorts.

A Survey of Rare Epigenetic Variation in 23,116 Human Genomes Identifies Disease-Relevant Epivariations and CGG Expansions.
Garg Paras et al. American journal of human genetics 2020 Sep (Posted: Sep 17, 2020 10AM)

Little information exists on the prevalence and distribution of rare epigenetic variation in populations. We performed a survey of methylation profiles from 23,116 individuals. Using a robust outlier approach, we identified 4,452 unique autosomal epivariations, including potentially inactivating promoter methylation events at 384 genes linked to disease.

Association of Epigenetic Metrics of Biological Age With Cortical Thickness
AL Proskovec et al, JAMA Network Open, September 14, 2020 (Posted: Sep 15, 2020 7AM)

In this study of 82 healthy adults, both biological and chronological age were associated with widespread cortical thinning, but biological age acceleration was also associated with additional changes in cortical morphology. Older biological age relative to chronological age was associated with accentuated thinning in prefrontal and temporal regions.

Epigenetic Therapies for Cancer
SE Bates. NEJM, August 12, 2020 (Posted: Aug 13, 2020 7AM)

Epigenetics is a field approaching its 50th anniversary. In 2020, despite the availability of nine approved epigenetic agents, most advances in the epigenetic treatment of hematologic cancers and solid tumors remain a work in progress.

What is Epigenetics?
CDC, August 2020 Brand (Posted: Aug 05, 2020 8AM)

While genetic changes can alter which protein is made, epigenetic changes affect gene expression to turn genes “on” and “off.” Since your environment and behaviors, such as diet and exercise, can result in epigenetic changes, it is easy to see the connection between your genes and your behaviors and environment.

Association of Neighborhood Disadvantage in Childhood With DNA Methylation in Young Adulthood
A Reuben et al, JAMA Network Open, June 1, 2020 (Posted: Jun 02, 2020 7AM)

The Role of Neighborhood Social Characteristics on the Epigenome—Why the Lack of Investigations?
EC Dunn, JAMA Network Open, June 1, 2020 (Posted: Jun 02, 2020 7AM)

Research to bring together multiple levels of analysis is critical because it can inform both etiological understanding and the design of interventions or policy approaches. Yet, few attempts have been made to systematically bridge these levels in empirical analyses.

Next-generation epigenetic inhibitors
Science, April 24, 2020 (Posted: Apr 26, 2020 10AM)

Epigenetic Therapeutics for Cardiovascular Disease- Writing, Erasing, Reading, and Maybe Forgetting
J Plutzky, JAMA, March 27, 2020 (Posted: Mar 28, 2020 8AM)

The identification of an epigenetic code operating above DNA to direct transcription and define phenotypes is still unfolding. The dynamic epigenetic processes of writing, erasing, and reading of histone marks allows humans to adapt to different inputs despite having a fixed genome at birth.

Mirror, Mirror, On The Wall: The Epigenetics Of Aging
E Matloff, Forbes, January 24, 2020 (Posted: Jan 25, 2020 8AM)

Unlike the DNA we are born with, epigenetic findings can change over the course of our lifetimes. It has been postulated that examining these epigenetic findings can be used to help determine our ‘true age,’ as opposed to the chronological age associated with our birthdate.

Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood
N Noor, JAMA Network OPen, December 27, 2019 (Posted: Dec 31, 2019 9AM)

This cohort study of 429 father-mother-infant triads found that paternal body mass index at the time of conception was associated with both offspring birth weight and epigenome-wide DNA methylation patterns in offspring at birth, age 3 years, and age 7 years.

New Tests Use Epigenetics to Guess How Fast You're Aging
MC Marill, WIRED< December 2019 (Posted: Dec 25, 2019 0PM)

Companies claim they can now easily calculate your biological age. Should you take them up on it? Commercial epigenetic testing is in its infancy, so consumers should be wary if companies make claims about a specific disease risk or offer to precisely predict lifespan—or use the results to market other products.

Cancer's epigenetic drugs: where are they in the cancer medicines?
Ghasemi Sorayya et al. The pharmacogenomics journal 2019 Dec (Posted: Dec 12, 2019 9AM)

Genomic Tools for Environmental Epigenetics and Implications for Public Health.
Perera Bambarendage P U et al. Current opinion in toxicology 2019 Dec 1827-33 (Posted: Dec 04, 2019 10AM)

The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.
McEwen Lisa M et al. Proceedings of the National Academy of Sciences of the United States of America 2019 Oct (Posted: Oct 16, 2019 6AM)

A decade of epigenetic change in aging twins: genetic and environmental contributions to longitudinal DNA methylation
CA Reynolds et al, BioRXIV, September 30, 2019 (Posted: Oct 02, 2019 8AM)

Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise
D Morel et al, Nat Rev Clin Oncology, September 30, 2019 (Posted: Oct 01, 2019 8AM)

The review provides a critical appraisal of the preclinical rationale, completed clinical studies and ongoing clinical trials relating to combination therapies incorporating epi-drugs.

Appraising the causal relevance of DNA methylation for risk of lung cancer.
Battram Thomas et al. International journal of epidemiology 2019 Sep (Posted: Sep 26, 2019 8AM)

DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.

First hint that body’s ‘biological age’ can be reversed-In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age.
A Abbot, Nature, September 2019 (Posted: Sep 08, 2019 7AM)

For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analyzing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.

Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing
Q Zhang et al, Genome Medicine, August 26, 2019 (Posted: Aug 27, 2019 7AM)

DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed ‘epigenetic clocks’. The deviation of predicted age from the actual age has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association.

Comprehensive longitudinal study of epigenetic mutations in aging
Y Wang et al, BioRXIV, AUgust 22, 2019 (Posted: Aug 23, 2019 1PM)

Using 994 blood samples collected at up to five time points from 375 individuals in old ages, the study verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, and cancer diagnosis.

Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1
DE Martin-Herranz et al, Genome Biology, August 15, 2019 (Posted: Aug 16, 2019 8AM)

Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
Speedy Helen E et al. Nature communications 2019 Aug (1) 3615 (Posted: Aug 12, 2019 8AM)

Making the transgenerational epigenetic inheritance of trauma real
A Stelmach et al, University of Nottingham, Blog, August 2019 (Posted: Aug 03, 2019 4PM)

Advances in epigenetics link genetics to the environment and disease.
Cavalli Giacomo et al. Nature 2019 Jul (7766) 489-499 (Posted: Jul 26, 2019 2PM)

Epigenetics comes to RNA
K Garber, Science, July 5, 2019 (Posted: Jul 05, 2019 9AM)

A map of human individuality.
Koch Linda et al. Nature reviews. Genetics 2019 Jun (Posted: Jul 01, 2019 9AM)

A great body of research into the human epigenome has focused on cell type-specific, dynamic DNA methylation patterns. Now, a study reports an atlas of systemic interindividual epigenetic variation. It highlights these genomic regions as a source of phenotypic variation in humans that correlates with gene expression and is associated with disease.

Epigenetic cancer evolution, one cell at a time
CN Perdigoto, Nature Rev Genetics, June 3, 2019 (Posted: Jun 03, 2019 1PM)

Points-to-consider on the return of results in epigenetic research.
Dyke Stephanie O M et al. Genome medicine 2019 May 11(1) 31 (Posted: May 29, 2019 8AM)

Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review.
Grau-Perez Maria et al. Current environmental health reports 2019 03 (1) 38-51 (Posted: May 12, 2019 2PM)

Epigenetics in Human Obesity and Type 2 Diabetes.
Ling Charlotte et al. Cell metabolism 2019 Apr (Posted: May 07, 2019 9AM)

Epigenetic-based therapy for colorectal cancer: Prospect and involved mechanisms.
Rezapour Saleheh et al. Journal of cellular physiology 2019 Apr (Posted: May 07, 2019 9AM)

Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy
KV Schulze et al. Genetics in Medicine, April 17, 2019 (Posted: Apr 17, 2019 8AM)

Epigenetics and child development: how children's experiences affect their genes
Harvard Center on the Developing Child, 2019 (Posted: Mar 11, 2019 10AM)

Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer
HP Mohammad et al, Nature Medicine, March 6, 2019 (Posted: Mar 07, 2019 9AM)

Alcohol and DNA Methylation: An Epigenome-Wide Association Study in Blood and Normal Breast Tissue
LE Wilson et al, AM J Epidemiology, February 15, 2019 (Posted: Feb 25, 2019 9AM)

Epigenetic Loci of Blood Pressure.
Syme Catriona et al. Circulation. Genomic and precision medicine 2019 Jan (1) e002341 (Posted: Jan 28, 2019 8AM)

NIH Roadmap Epigenomics Mapping Consortium
January 2019 Brand (Posted: Jan 15, 2019 0PM)

Genomic imprinting disorders: lessons on how genome, epigenome and environment interact
D Monk et al, Nature Rev Genetics, January 15, 2019 (Posted: Jan 15, 2019 10AM)

Epigenetics may hold key to arsenic’s role in cancer
E Hood, The Environmental Factors, NIEHS, January 2019 Brand (Posted: Jan 15, 2019 9AM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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