Human metabolic profiles are stably controlled by genetic and environmental variation

Journal article

1 H Nuclear Magnetic Resonance spectroscopy (1 H 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 1 H 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 1 H 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 1 H NMR-based biomarkers quantifying predisposition to disease. © 2011 EMBO and Macmillan Publishers Limited All rights reserved.

Authors: Nicholson, G; Rantalainen, M; Maher, A; Li, J; Malmodin, D

• Journal: Molecular Systems Biology
• Volume: 7
• Publication date: 2011-01-01
• DOI: 10.1038/msb.2011.57
• EISSN: 1744-4292
• Language: English
• Keywords: variance decomposition; top-down systems biology; biomarker; 1H nuclear magnetic resonance spectroscopy; metabolome-wide association study