Human metabolic profiles are stably controlled by genetic and environmental variation.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797103438951088128 |
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| author | Nicholson, G Rantalainen, M Maher, A Li, J Malmodin, D Ahmadi, K Faber, J Hallgrímsdóttir, I Barrett, A Toft, H Krestyaninova, M Viksna, J Neogi, S Dumas, M Sarkans, U The Molpage Consortium Silverman, B Donnelly, P Nicholson, J Allen, M Zondervan, K Lindon, J Spector, T McCarthy, M Holmes, E |
| author_facet | Nicholson, G Rantalainen, M Maher, A Li, J Malmodin, D Ahmadi, K Faber, J Hallgrímsdóttir, I Barrett, A Toft, H Krestyaninova, M Viksna, J Neogi, S Dumas, M Sarkans, U The Molpage Consortium Silverman, B Donnelly, P Nicholson, J Allen, M Zondervan, K Lindon, J Spector, T McCarthy, M Holmes, E |
| author_sort | Nicholson, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:20:07Z |
| format | Journal article |
| id | oxford-uuid:f2719abd-be7a-4bfb-b132-e5277a0b9e04 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:20:07Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:f2719abd-be7a-4bfb-b132-e5277a0b9e042022-03-27T12:03:55ZHuman metabolic profiles are stably controlled by genetic and environmental variation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f2719abd-be7a-4bfb-b132-e5277a0b9e04EnglishSymplectic Elements at Oxford2011Nicholson, GRantalainen, MMaher, ALi, JMalmodin, DAhmadi, KFaber, JHallgrímsdóttir, IBarrett, AToft, HKrestyaninova, MViksna, JNeogi, SDumas, MSarkans, UThe Molpage ConsortiumSilverman, BDonnelly, PNicholson, JAllen, MZondervan, KLindon, JSpector, TMcCarthy, MHolmes, E¹H 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. |
| spellingShingle | Nicholson, G Rantalainen, M Maher, A Li, J Malmodin, D Ahmadi, K Faber, J Hallgrímsdóttir, I Barrett, A Toft, H Krestyaninova, M Viksna, J Neogi, S Dumas, M Sarkans, U The Molpage Consortium Silverman, B Donnelly, P Nicholson, J Allen, M Zondervan, K Lindon, J Spector, T McCarthy, M Holmes, E Human metabolic profiles are stably controlled by genetic and environmental variation. |
| title | Human metabolic profiles are stably controlled by genetic and environmental variation. |
| title_full | Human metabolic profiles are stably controlled by genetic and environmental variation. |
| title_fullStr | Human metabolic profiles are stably controlled by genetic and environmental variation. |
| title_full_unstemmed | Human metabolic profiles are stably controlled by genetic and environmental variation. |
| title_short | Human metabolic profiles are stably controlled by genetic and environmental variation. |
| title_sort | human metabolic profiles are stably controlled by genetic and environmental variation |
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