For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
198
views
30
references
 Top references
cited by
122
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      282
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Blood Exposome and Its Role in Discovering Causes of Disease

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Since 2001, researchers have examined the human genome (G) mainly to discover causes of disease, despite evidence that G explains relatively little risk. We posit that unexplained disease risks are caused by the exposome (E; representing all exposures) and G × E interactions. Thus, etiologic research has been hampered by scientists’ continuing reliance on low-tech methods to characterize E compared with high-tech omics for characterizing G.

          Objectives: Because exposures are inherently chemical in nature and arise from both endogenous and exogenous sources, blood specimens can be used to characterize exposomes. To explore the “blood exposome” and its connection to disease, we sought human blood concentrations of many chemicals, along with their sources, evidence of chronic-disease risks, and numbers of metabolic pathways.

          Methods: From the literature we obtained human blood concentrations of 1,561 small molecules and metals derived from foods, drugs, pollutants, and endogenous processes. We mapped chemical similarities after weighting by blood concentrations, disease-risk citations, and numbers of human metabolic pathways.

          Results: Blood concentrations spanned 11 orders of magnitude and were indistinguishable for endogenous and food chemicals and drugs, whereas those of pollutants were 1,000 times lower. Chemical similarities mapped by disease risks were equally distributed by source categories, but those mapped by metabolic pathways were dominated by endogenous molecules and essential nutrients.

          Conclusions: For studies of disease etiology, the complexity of human exposures motivates characterization of the blood exposome, which includes all biologically active chemicals. Because most small molecules in blood are not human metabolites, investigations of causal pathways should expand beyond the endogenous metabolome.

          Citation: Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A. 2014. The blood exposome and its role in discovering causes of disease. Environ Health Perspect 122:769–774;  http://dx.doi.org/10.1289/ehp.1308015

          Related collections

          Most cited references30

          • Record: found
          • Abstract: found
          • Article: not found

          A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010

          Stephen S Lim, Theo Vos, Abraham D. Flaxman … (2012)
          The Lancet, 380(9859), 2224-2260
          Article 0 comments Cited 3823 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases.

            B. N. Ames (1983)
            The human diet contains a great variety of natural mutagens and carcinogens, as well as many natural antimutagens and anticarcinogens. Many of these mutagens and carcinogens may act through the generation of oxygen radicals. Oxygen radicals may also play a major role as endogenous initiators of degenerative processes, such as DNA damage and mutation (and promotion), that may be related to cancer, heart disease, and aging. Dietary intake of natural antioxidants could be an important aspect of the body's defense mechanism against these agents. Many antioxidants are being identified as anticarcinogens. Characterizing and optimizing such defense systems may be an important part of a strategy of minimizing cancer and other age-related diseases.
            Article 0 comments Cited 305 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Human metabolic phenotype diversity and its association with diet and blood pressure.

              Elaine Holmes, Ruey Leng Loo, Jeremiah Stamler … (2008)
              Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.
              Article 0 comments Cited 303 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Environ Health Perspect
                Journal ID (iso-abbrev): Environ. Health Perspect
                Journal ID (publisher-id): EHP
                Title: Environmental Health Perspectives
                Publisher: NLM-Export
                ISSN (Print): 0091-6765
                ISSN (Electronic): 1552-9924
                Publication date (Electronic): 21 March 2014
                Publication date (Print): August 2014
                Volume: 122
                Issue: 8
                Pages: 769-774
                Affiliations
                [1 ]Center for Exposure Biology, School of Public Health, University of California, Berkeley, Berkeley, California, USA
                [2 ]Nutrition and Metabolism Section, Biomarkers Group, International Agency for Research on Cancer, Lyon, France
                [3 ]Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
                [4 ]MRC-PHE (Medical Research Council–Public Health England) Centre for Environment and Health, School of Public Health, Imperial College, London United Kingdom
                [5 ]HuGeF (Human Genetics Foundation), Torino, Italy
                Author notes
                Address correspondence to S.M. Rappaport, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-7356 USA. Telephone: (510) 642-4355. E-mail: srappaport@ 123456berkeley.edu
                Article
                Publisher ID: ehp.1308015
                DOI: 10.1289/ehp.1308015
                PMC ID: 4123034
                PubMed ID: 24659601
                SO-VID: 20247de3-6534-47cb-b175-0ab47c7b6c67
                License:

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                Date received : 16 December 2013
                Date accepted : 20 March 2014
                Date: 21 March 2014
                Date: 01 August 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Public health
                Data availability:
                ScienceOpen disciplines: Public health

                Comments

                Comment on this article

                scite_

                Similar content282

                See all similar

                Cited by117

                See all cited by

                Most referenced authors3,619

                See all reference authors