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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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Abstract

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
Authors :
NameEmailORCID
Nicholson, GUNSPECIFIEDUNSPECIFIED
Rantalainen, MUNSPECIFIEDUNSPECIFIED
Hallgrímsdóttir, IBUNSPECIFIEDUNSPECIFIED
Silverman, BWUNSPECIFIEDUNSPECIFIED
Donnelly, PUNSPECIFIEDUNSPECIFIED
Holmes, CCUNSPECIFIEDUNSPECIFIED
Maher, ADUNSPECIFIEDUNSPECIFIED
Li, JVUNSPECIFIEDUNSPECIFIED
Dumas, M-EUNSPECIFIEDUNSPECIFIED
Nicholson, JKUNSPECIFIEDUNSPECIFIED
Lindon, JCUNSPECIFIEDUNSPECIFIED
Holmes, EUNSPECIFIEDUNSPECIFIED
Malmodin, DUNSPECIFIEDUNSPECIFIED
Faber, JHUNSPECIFIEDUNSPECIFIED
Toft, HUNSPECIFIEDUNSPECIFIED
Baunsgaard, DUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Spector, TDUNSPECIFIEDUNSPECIFIED
Barrett, AUNSPECIFIEDUNSPECIFIED
Allen, MUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
Krestyaninova, MUNSPECIFIEDUNSPECIFIED
Sarkans, UUNSPECIFIEDUNSPECIFIED
Viksna, JUNSPECIFIEDUNSPECIFIED
Neogi, SGUNSPECIFIEDUNSPECIFIED
Maher, ADUNSPECIFIEDUNSPECIFIED
Silverman, BWUNSPECIFIEDUNSPECIFIED
Donnelly, PUNSPECIFIEDUNSPECIFIED
Zondervan, KTUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
Date : 2011
Identification Number : 10.1038/msb.2011.57
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:35
Last Modified : 17 May 2017 14:43
URI: http://epubs.surrey.ac.uk/id/eprint/824335

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