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Human metabolic profiles are stably controlled by genetic and environmental variation

Nicholson, G, Rantalainen, M, Hallgrímsdóttir, IB, Silverman, BW, Donnelly, P, Holmes, CC, Maher, AD, Li, JV, Dumas, M-E, Nicholson, JK , Lindon, JC, Holmes, E, Malmodin, D, Faber, JH, Toft, H, Baunsgaard, D, Ahmadi, KR, Spector, TD, Barrett, A, Allen, M, McCarthy, MI, Krestyaninova, M, Sarkans, U, Viksna, J, Neogi, SG, Maher, AD, Silverman, BW, Donnelly, P, Zondervan, KT and McCarthy, MI (2011) Human metabolic profiles are stably controlled by genetic and environmental variation Molecular Systems Biology, 7.

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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.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Nicholson, G
Rantalainen, M
Hallgrímsdóttir, IB
Silverman, BW
Donnelly, P
Holmes, CC
Maher, AD
Li, JV
Dumas, M-E
Nicholson, JK
Lindon, JC
Holmes, E
Malmodin, D
Faber, JH
Toft, H
Baunsgaard, D
Spector, TD
Barrett, A
Allen, M
McCarthy, MI
Krestyaninova, M
Sarkans, U
Viksna, J
Neogi, SG
Maher, AD
Silverman, BW
Donnelly, P
Zondervan, KT
McCarthy, MI
Date : 2011
DOI : 10.1038/msb.2011.57
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:35
Last Modified : 24 Jan 2020 17:14

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