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

Journal article

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.

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

• Publication status: Published
• Journal: Molecular systems biology
• Volume: 7
• Pages: 525
• Publication date: 2011-01-01
• DOI: 10.1038/msb.2011.57
• EISSN: 1744-4292
• ISSN: 1744-4292
• Language: English
• Keywords: Metabolome; Databases, Genetic; Sample Size; Humans; Aged; Research Design; European Continental Ancestry Group; Genetic Variation; Biological Markers; Gene-Environment Interaction; Nuclear Magnetic Resonance, Biomolecular; Female; Twins, Monozygotic; Systems Biology; Models, Statistical; Twins, Dizygotic; Algorithms; Middle Aged