Human metabolic profiles are stably controlled by genetic and environmental variation.
Mol Syst Biol
; 7: 525, 2011 Aug 30.
Article
em En
| MEDLINE
| ID: mdl-21878913
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores
/
Ressonância Magnética Nuclear Biomolecular
/
População Branca
/
Biologia de Sistemas
/
Metaboloma
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Interação Gene-Ambiente
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
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Humans
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Middle aged
Idioma:
En
Revista:
Mol Syst Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido