Metabolomics in epidemiology: sources of variability in metabolite measurements and implications.

Authors

Sampson JN, Boca SM, Shu XO, Stolzenberg-Solomon RZ, Matthews CE, Hsing AW, Tan YT, Ji BT, Chow WH, Cai Q, Liu DK, Yang G, Xiang YB, Zheng W, Sinha R, Cross AJ, Moore SC

Affiliations

• Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rockville, MD 20852, USA. joshua.sampson@nih.gov

Abstract

BACKGROUND: Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiologic studies to detect associations with disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies.

METHODS: Using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography-mass spectroscopy (GC/MS) platforms, 385 metabolites were measured in 60 women at baseline and year-one of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study.

RESULTS: Although the authors found high technical reliability (median intraclass correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a relative risk of 3 (comparing upper and lower quartiles of "usual" levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74%, and 97% of studies including 500, 1,000, and 5,000 individuals. Age, gender, and fasting status factors, which are often of less interest in epidemiologic studies, were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak and explained only a small proportion of the total metabolite variability.

CONCLUSION: Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies.

IMPACT: We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology.