EPA Workshop on Epigenetics and Cumulative Risk Assessment

[UPDATE] Thank you for attending the EPA Workshop on Epigenetics and Cumulative Risk Assessment on September 2-3, 2015. The workshop materials, agenda, and a glossary of epigenetic terms are available from the tabs below.

General Scope of the Workshop

  • To examine current understanding of the impacts of a variety of stressors on epigenetic status.
  • To appraise the potential to use epigenetic change as a measure of cumulative, multi-stressor, exposure and impact.
  • To define research and practical needs to advance epigenetics as a potential tool for cumulative risk assessment.


The meeting was held on September 2-3, 2015 from 8:30 am - 5:30pm Eastern Time.


The workshop was held in the EPA Conference Center at 2777 South Crystal Drive, Arlington, Virginia 22202. The workshop was also available by webinar/teleconference.


Identifying the genetic and environmental determinants of human health and disease is a major challenge in biomedical research. Investments in the human genome project (HGP) have transformed our understanding of the contribution of genetics and the environment to the etiology of chronic non-communicable diseases.

For example, we now know that genes do not determine biological fate; they establish a range of possible phenotypic outcomes through complex interactions with the environment. Because of this, genetics by itself is not an effective predictor of the development of disease. Environmental factors that contribute to disease outcome are broadly defined and include dietary imbalance, environmental pollution, effects of economic deprivation, and psychosocial stress. There is now an abundance of evidence demonstrating the existence of both genetic and epigenetic pathways for regulating gene expression. Whereas the genetic pathway is well understood, the epigenetic pathway is poorly understood. To date, the three best known epigenetic mechanisms involve DNA methylation, histone modification, and alteration of the expression of micro-RNAs. Research has also linked a wide range of stressors including pollution and social factors with the occurrence of epigenetic alterations. These potentially durable epigenetic modifications induced by both genetic and environmental exposures, provide another explanation for how genes and the environment interact to influence human health and disease. The biological relevance of these findings is supported by the fact that the level of intensity of DNA methylation is dose-dependent and results are reproducible from experiment to experiment, and from laboratory to laboratory.

The success of genome-wide association studies (GWAS) in identifying diseases associated with specific genetic variants, based on the existence of high resolution maps of single nucleotide polymorphisms (SNPs), suggests that a complimentary epigenome-wide association study (EWAS), based on knowledge of tissue-specific epigenetic modifications now being generated by the International Human Epigenome Consortium (IHEC), may be fruitful in associating environmental exposures to disease.

The EWAS is examining the distribution of epigenetic modifications at thousands of loci across the genome to discover patterns that are specific to a given disease or environmental exposure. This may be a particularly powerful approach to investigate the putative role of the environment or “neighborhood effect” in health disparities. Several lines of evidence support the view that adverse environmental exposures during early development increase susceptibility to multiple diseases (e.g., cardiovascular disease, type 2 diabetes, osteoporosis, obstructive lung and mental health disorders). This “developmental origin of disease hypothesis” is supported by extensive epidemiologic and animal studies. Furthermore, studies show that epigenetic modifications can occur both before and after overt disease is evident, suggesting that they may play a role in initiation and progression of the disease.

Building on this information and more recent advances discussed by participants, this workshop will advance our understanding of the interplay between cumulative exposure to environmental stress, epigenetic change, and the development of disease.

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Download the Workshop Agenda (PDF)
The workshop included presentations and discussions by scientific experts pertaining to three topics (i.e., epigenetic changes associated with diverse stressors, key science considerations in understanding epigenetic changes, and practical application of epigenetic tools to address cumulative risks from environmental stressors), to address several questions under each topic, and included an opportunity for attendees to participate in break-out groups, provide comments and ask questions.

Workshop Goals

The workshop seeks to examine the opportunity for use of aggregate epigenetic change as an indicator in cumulative risk assessment for populations exposed to multiple stressors that affect epigenetic status.

Epigenetic changes are specific molecular changes around DNA that alter expression of genes. Epigenetic changes include DNA methylation, formation of histone adducts, and changes in micro RNAs. Research today indicates that epigenetic changes are involved in many chronic diseases (cancer, cardiovascular disease, obesity, diabetes, mental health disorders, and asthma). Research has also linked a wide range of stressors including pollution and social factors with occurrence of epigenetic alterations. Epigenetic changes have the potential to reflect impacts of risk factors across multiple stages of life.

Only recently receiving attention is the nexus between the factors of cumulative exposure to environmental stress, epigenetic change, and the development of chronic disease. In the terminology of environmental science, epigenetic changes may be able to play a role as both biosensors of cumulative exposure and biomarkers of effect for disease processes.

This workshop examined the concept of "epigenetic load" - accumulated epigenetic marks as influenced by multiple stressors - and how it can inform cumulative risk assessment. Important questions for understanding as the field develops include possible "tipping points" for cumulative epigenetic change, which when exceeded would compromise health. And whether, in a population already exposed to significant stressors, an additional stress (even if not large in magnitude) can lead to some increase in the probability of disease.

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