Exposome

The exposome encompasses the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome. It was first proposed by Dr. Christopher Wild, a cancer epidemiologist, in a 2005 article entitled "Complementing the Genome with an “Exposome”: The Outstanding Challenge of Environmental Exposure Measurement in Molecular Epidemiology".^[1] The concept of the exposome and how to assess it has led to lively discussions with varied views.^{[2][3][4][5][6][7][8][9][10][11]} Although at this stage it may not be possible to measure or model the full exposome, some recent European projects such as HELIX,^[8][12] EXPOsOMICS,^[13][14] and HEALS^[15] and the American initiative HERCULES ^[16] have started to make first attempts.

Background

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 etiologic research, in order to balance the investment, tools and knowledge in genetics. Wild also stated that even incomplete versions of the exposome could be of great use to field of epidemiology. Wild published a follow-up paper in 2012 where he outlines methods, including personal sensors, biomarkers and 'omics' technologies, to better define the exposome.^[4] He has described three overlapping domains within the exposome:

1. a general external environment including the urban environment, climate factors, social capital, stress,
2. a specific external environment with specific contaminants, diet, physical activity, tobacco, infections, etc., and
3. an internal environment to include internal biological factors such as metabolic factors, gut microflora, inflammation, oxidative stress.

More recently, G.W. Miller and D. P. Jones proposed a revised definition of the exposome that explicitly incorporates the body's response to environmental influences and also includes the endogenous metabolic processes that can alter or process the chemicals to which humans are exposed.^[17] This definition is explained in greater depth in the new book by G.W. Miller entitled "The Exposome: A Primer" published by Elsevier in late 2013.^[18] This introductory text is the first book on the exposome and explores the gene versus environmental argument.^[19]

For complex disorders specific genetic causes appear to only account for 10-30% of the disease incidence, although as genomic approaches improve this percentage could increase. Environmental influences contribute to human disease, but unlike with genetics, there is no standard or systematic way to measure the influence of environmental exposures. Some studies, such as those by C. J. Patel et al into the interaction of genetic and environmental factors in the incidence of diabetes have demonstrated that environmental-wide association studies (EWAS, or exposome-wide association studies) may be feasible.^[20][21] However, it is not clear what data sets are most appropriate to represent the value of "E".^[22]

Research initiatives

In 2012, the European Commission awarded two large-grants to pursue exposome-related research.^[23] The HELIX project at the Barcelona-based Centre for Research in Environmental Epidemiology will attempt to develop an early life exposome, noting that the first exposures occur during development.^[8][12] 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. The second project, Exposomics, led by Paolo Vineis, is a consortium based at Imperial College London.^[24] This project will use smartphones that utilize GPS and environmental sensors to assess exposures. Another major initiative that started in late 2013 is the Health and Environment-Wide Associations based on Large Scale population Surveys or HEALS. Touted as the largest environmental health-related study in Europe, HEALS proposes to reverse the paradigm of “nature versus nurture” and adopt one defined by complex and dynamic interactions between DNA sequence, epigenetic DNA modifications, gene expression and environmental factors that all combine to influence disease phenotypes.^[25]

In the US, the National Academy of Sciences hosted a meeting in December 2011 entitled "Emerging Technologies for Measuring Individual Exposomes."^[26] 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.^[10] The National Institutes of Health (NIH) has made investments in technologies that support exposome-related research, including biosensors, and supports research on gene-environment interactions.^[27][28] In May, 2013, the National Institute of Environmental Health Sciences (NIEHS) awarded a Core Center Grant to Emory University that is focused on the exposome.^[29]

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 no such project exists at this time. Several investigators have argued that such an initiative should occur, but given the lack of clarity on how science would go about pursuing such a project, support has been lacking.^[30] 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" was published in the journal Environmental Health Perspectives.^[31]
• "Exposure Science in the 21st Century: A Vision and A Strategy", an official report from the United States National Research Council published in September 2012 outlines the challenges in implementing systematic evaluation of the exposome.^[32][33]

Related fields

The concept of exposome contributes to a new paradigm in disease phenotype. Essentially, an individual has a unique disease process different from any other individual ("the unique disease principle"), considering uniqueness of the exposome and its unique influence on molecular pathologic processes (including alterations in the interactome) in each individual.^[34] This principle was first described in neoplastic diseases as "the unique tumor principle".^[35] Based on this unique disease principle, interdisciplinary field of molecular pathological epidemiology (MPE) emerged as an integration of molecular pathology and epidemiology.^[36] Because heterogeneity of exposome, disease etiology, and pathogenesis is a ubiquitous phenomenon, the MPE paradigm will become inherent in epidemiology and population health science.

See also

• Envirome
• Epidemiology
• Human Toxome Project^[37]
• Molecular epidemiology
• Molecular pathological epidemiology
• Public health

References