Metabolic profiling and the metabolome-wide association study: significance level for biomarker identification.

ABSTRACT: High throughput metabolic profiling via the metabolome-wide association study (MWAS) is a powerful new approach to identify biomarkers of disease risk, but there are methodological challenges: high dimensionality, high level of collinearity, the existence of peak overlap within metabolic spectral data, multiple testing, and selection of a suitable significance threshold. We define the metabolome-wide significance level (MWSL) as the threshold required to control the family wise error rate through a permutation approach. We used 1H NMR spectroscopic profiles of 24 h urinary collections from the INTERMAP study. Our results show that the MWSL primarily depends on sample size and spectral resolution. The MWSL estimates can be used to guide selection of discriminatory biomarkers in MWA studies.

SUBMITTER: Chadeau-Hyam M 

PROVIDER: S-EPMC2941198 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature