¹H Nuclear Magnetic Resonance spectroscopy (¹H NMR) is increasingly used to measure metabolite concentrations in sets of biological samples for top-down systems biology and molecular epidemiology. For such purposes, knowledge of the sources of human variation in metabolite concentrations is valuable, but currently sparse. We conducted and analysed a study to create such a resource. In our unique design, identical and non-identical twin pairs donated plasma and urine samples longitudinally. We acquired ¹H NMR spectra on the samples, and statistically decomposed variation in metabolite concentration into familial (genetic and common-environmental), individual-environmental, and longitudinally unstable components. We estimate that stable variation, comprising familial and individual-environmental factors, accounts on average for 60% (plasma) and 47% (urine) of biological variation in ¹H NMR-detectable metabolite concentrations. Clinically predictive metabolic variation is likely nested within this stable component, so our results have implications for the effective design of biomarker-discovery studies. We provide a power-calculation method which reveals that sample sizes of a few thousand should offer sufficient statistical precision to detect ¹H NMR-based biomarkers quantifying predisposition to disease.

Original publication

DOI

10.1038/msb.2011.57

Type

Journal article

Journal

Mol Syst Biol

Publication Date

30/08/2011

Volume

7

Keywords

Aged, Algorithms, Biomarkers, Databases, Genetic, European Continental Ancestry Group, Female, Gene-Environment Interaction, Genetic Variation, Humans, Metabolome, Middle Aged, Models, Statistical, Nuclear Magnetic Resonance, Biomolecular, Research Design, Sample Size, Systems Biology, Twins, Dizygotic, Twins, Monozygotic