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Mol Syst Biol. 2011 Aug 30;7:525. doi: 10.1038/msb.2011.57.

Human metabolic profiles are stably controlled by genetic and environmental variation.

Author information

1
Department of Statistics, University of Oxford, Oxford, UK. nicholso@stats.ox.ac.uk

Abstract

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.

PMID:
21878913
PMCID:
PMC3202796
DOI:
10.1038/msb.2011.57
[Indexed for MEDLINE]
Free PMC Article

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