The exposome encompasses the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome, first proposed in 2005 by a cancer epidemiologist. The concept of the exposome and how to assess it has led to lively discussions with varied views. As of 2016 it may not be possible to measure or model the full exposome, several European projects such as HELIX, EXPOsOMICS, and HEALS and the U.S. initiative HERCULES have started to make first attempts.
The exposome encompasses the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome. It was first proposed in 2005 by a cancer epidemiologist, in an article entitled "Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology". The concept of the exposome and how to assess it has led to lively discussions with varied views in 2010,2012 and 2014,
In his 2005 article Wild stated, "At its most complete, the exposome encompasses life-course environmental exposures (including lifestyle factors), from the prenatal period onwards." The concept was first proposed to draw attention to the need for better and more complete environmental exposure data for causal research, in order to balance the investment in genetics. Per Wild even incomplete versions of the exposome could be useful to epidemiology. In 2012 Wild outlined methods, including personal sensors, biomarkers and 'omics' technologies, to better define the exposome. He described three overlapping domains within the exposome:
- a general external environment including the urban environment, education, climate factors, social capital, stress,
- a specific external environment with specific contaminants, radiation, infections, lifestyle factors (e.g. tobacco, alcohol), diet, physical activity, etc.
- an internal environment to include internal biological factors such as metabolic factors, hormones, gut microflora, inflammation, oxidative stress.
In late 2013 this definition was explained in greater depth in the first book on the exposome. In 2014, the same author revised the definition to include the body's response with its endogenous metabolic processes which alter processing of chemicals.
For complex disorders specific genetic causes appear to only account for 10-30% of the disease incidence, but there has been no standard or systematic way to measure the influence of environmental exposures. Some studies into the interaction of genetic and environmental factors in the incidence of diabetes have demonstrated that "environment-wide association studies" (EWAS, or exposome-wide association studies) may be feasible. However, it is not clear what data sets are most appropriate to represent the value of "E".
In July 2017, saliva was suggested as a practical specimen to measure the human exposome, and because it is easy to collect, to analyse it repeatedly in longitudinal EWAS. The authors found concentrations of 1,233 chemicals and 169 metabolites had been detected in saliva per their literature and saliva–metabolome database review, which fit into 49 metabolic pathways.
As of 2016 it may not be possible to measure or model the full exposome, but several European projects have started to make first attempts. In 2012, the European Commission awarded two large-grants to pursue exposome-related research.
The HELIX project at the Barcelona-based Centre for Research in Environmental Epidemiology will attempt[when?] to develop an early life exposome, noting that the first exposures occur during development. It will build upon six existing birth cohorts across Europe and measure the exposome at key prenatal and early childhood time points, through the use of GIS, personal sensors, biomarkers and omics platforms.
In late 2013, a major initiative called the "Health and Environment-Wide Associations based on Large Scale population Surveys" or HEALS began. Touted as the largest environmental health-related study in Europe, HEALS proposes to adopt a paradigm defined by interactions between DNA sequence, epigenetic DNA modifications, gene expression and environmental factors.
In December 2011, the US National Academy of Sciences hosted a meeting entitled "Emerging Technologies for Measuring Individual Exposomes." A Centers for Disease Control and Prevention overview "Exposome and Exposomics" outlines the three priority areas for researching the occupational exposome as identified by the National Institute for Occupational Safety and Health. The National Institutes of Health (NIH) has invested in technologies supporting exposome-related research, including biosensors, and supports research on gene-environment interactions. In May, 2013, the National Institute of Environmental Health Sciences (NIEHS) awarded a Core Center Grant to Emory University´s exposome project HERCULES. 
Proposed Human Exposome Project (HEP)
The idea of a Human Exposome Project, analogous to the Human Genome Project, has been proposed and discussed in numerous scientific meetings, but as of 2017 no such project exists. Given the lack of clarity on how science would go about pursuing such a project, support has been lacking. Reports on the issue include:
- a 2011 review on the exposome and exposure science by Paul Lioy and Stephen Rappaport, "Exposure science and the exposome: an opportunity for coherence in the environmental health sciences" in the journal Environmental Health Perspectives.
- a 2012 report from the United States National Research Council "Exposure Science in the 21st Century: A Vision and A Strategy", outlining the challenges in systematic evaluations of the exposome.
The concept of exposome has contributed to the 2010 proposal of a new paradigm in disease phenotype, "the unique disease principle": Every individual has a unique disease process different from any other individual, considering uniqueness of the exposome and its unique influence on molecular pathologic processes including alterations in the interactome. This principle was first described in neoplastic diseases as "the unique tumor principle". Based on this unique disease principle, the interdisciplinary field of molecular pathological epidemiology (MPE) integrates molecular pathology and epidemiology.
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- Rappaport SM, Smith MT (2010). "Epidemiology. Environment and disease risks". Science. 330 (6003): 460–461. doi:10.1126/science.1192603.
- Rappaport SM (2011). "Implications of the exposome for exposure science". J Expo Sci Environ Epidemiol. 21 (1): 5–9. doi:10.1038/jes.2010.50.
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