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Discovering environmental causes of disease
  1. Stephen M Rappaport
  1. Correspondence to Professor Stephen M Rappaport, School of Public Health, University of California, Berkeley, CA 94720-7356, USA; srappaport{at}


Although chronic diseases are primarily environmental (ie, not genetic) in origin, the particular environmental causes of these diseases are poorly understood. A WHO study of worldwide cancer mortality identified nine diverse environmental factors, including pollution, diet, lifestyle factors and infections. However, the joint effect of these nine factors accounted for only about one-third of cancer mortality, indicating that about two-thirds are of unknown aetiology. One problem relates to the community of epidemiologists, which sorts environmental factors into marginally overlapping domains, thereby creating gaps in coverage. Also, information about environmental exposures in epidemiologic studies is generally derived from questionnaires that are ill suited for assessing thousands of potentially causative exposures. Finally, the few studies that rigorously estimate exposure levels focus upon a handful of pollutants of regulatory importance and thus are unsuited for finding hitherto unrecognised exposures from both exogenous and endogenous sources. The concept of the ‘exposome’—representing the totality of exposures from gestation onwards—has recently been introduced as a complement to the genome in studies of disease aetiology. The exposome concept promotes environmental analogues of genome-wide association studies, which employ untargeted omic methods to compare biospecimens from diseased and healthy subjects. The goal of such investigations is to discover key biomarkers of exposure that enable follow-up hypotheses to be explored regarding sources of exposure, dose–response relationships, mechanisms of action, disease causality and public health interventions. Examples of this approach are cited from recent metabolomic studies of several complex chronic diseases.

  • exposome
  • environment
  • exposure
  • disease aetiology
  • metabolomics
  • environmental health
  • measurement
  • occupational health

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  • Addendum: In an effort to introduce the exposome concept to the environmental health sciences, the US National Institute for Environmental Health Sciences requested that the National Academy of Sciences convene workshops to discuss implications of the exposome for understanding the causes of human diseases (25–26 February 2010) and methods for characterising individual exposomes (8–9 December 2011). Information is available at about both workshops.

  • Funding This study was supported by grant U54ES016115 from the National Institute for Environmental Health Sciences.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.