Opening up the "Black Box": metabolic phenotyping and metabolome-wide association studies in epidemiology

J Clin Epidemiol. 2010 Sep;63(9):970-9. doi: 10.1016/j.jclinepi.2009.10.001. Epub 2010 Jan 8.

Abstract

Background: Metabolic phenotyping of humans allows information to be captured on the interactions between dietary, xenobiotic, other lifestyle and environmental exposures, and genetic variation, which together influence the balance between health and disease risks at both individual and population levels.

Objectives: We describe here the main procedures in large-scale metabolic phenotyping and their application to metabolome-wide association (MWA) studies.

Methods: By use of high-throughput technologies and advanced spectroscopic methods, application of metabolic profiling to large-scale epidemiologic sample collections, including metabolome-wide association (MWA) studies for biomarker discovery and identification.

Discussion: Metabolic profiling at epidemiologic scale requires optimization of experimental protocol to maximize reproducibility, sensitivity, and quantitative reliability, and to reduce analytical drift. Customized multivariate statistical modeling approaches are needed for effective data visualization and biomarker discovery with control for false-positive associations since 100s or 1,000s of complex metabolic spectra are being processed.

Conclusion: Metabolic profiling is an exciting addition to the armamentarium of the epidemiologist for the discovery of new disease-risk biomarkers and diagnostics, and to provide novel insights into etiology, biological mechanisms, and pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / metabolism
  • Humans
  • Metabolome / genetics*
  • Metabolomics / methods*
  • Metabolomics / standards
  • Molecular Epidemiology / standards*
  • Phenotype
  • Reproducibility of Results
  • Risk Assessment

Substances

  • Biomarkers