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

TitleOpening up the "Black Box": metabolic phenotyping and metabolome-wide association studies in epidemiology.
Publication TypeJournal Article
Year of Publication2010
AuthorsBictash M, Ebbels TM, Chan Q, Loo R L, Yap IKS, Brown IJ, De Iorio M, Daviglus ML, Holmes E, Stamler J, Nicholson JK, Elliott P
JournalJ Clin Epidemiol
Volume63
Issue9
Pagination970-9
Date Published2010 Sep
ISSN1878-5921
KeywordsBiological Markers, Humans, Metabolome, Metabolomics, Molecular Epidemiology, Phenotype, Reproducibility of Results, Risk Assessment
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.

DOI10.1016/j.jclinepi.2009.10.001
Alternate JournalJ Clin Epidemiol
PubMed ID20056386
PubMed Central IDPMC4048926
Grant ListG0801056 / / Medical Research Council / United Kingdom
R01 HL050490 / HL / NHLBI NIH HHS / United States
R01 HL050490-15 / HL / NHLBI NIH HHS / United States
R01 HL084228 / HL / NHLBI NIH HHS / United States
R01 HL084228 / HL / NHLBI NIH HHS / United States
R01 HL084228-03 / HL / NHLBI NIH HHS / United States
R01 HL50490 / HL / NHLBI NIH HHS / United States