The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Human metabolic profiles are stably controlled by genetic and environmental variation
Open accessAbstract
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.
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Cites
Gelman, A. (2006) · Bayesian Analysis · doi:10.1214/06-ba117a · Cited by 4,050 · cited 1×
“…corresponding variance parameter (denoted by su 2), was defined to be: pðujs2uÞ qðujm ¼ 0;s2 ¼ s2u; n ¼ 1; d ¼ 0:1Þ: Independent Uniform priors were placed on the standard deviation parameters (Gelman, 2006), p(s)BUniform(s|0, 10 sy), where sy denotes the sample standard deviation of the data, y.”
Methodology for Genetic Studies of Twins and Families
Neale, M. C., & Cardon, L. R. (1992) · doi:10.1007/978-94-015-8018-2 · Cited by 4,005
Creatine and Creatinine Metabolism
Wyss, M., & Kaddurah-Daouk, R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.1107 · Cited by 2,950
Human metabolic phenotype diversity and its association with diet and blood pressure
Holmes, E., Loo, R. L., Stamler, J., Bictash, M., Yap, I. K. S., Chan, Q., Ebbels, T., De Iorio, M., Brown, I. J., Veselkov, K. A., et al. (2008) · Nature · doi:10.1038/nature06882 · Cited by 1,054
Self-citationGenetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum
Gieger, C., Geistlinger, L., Altmaier, E., Hrabé de Angelis, M., Kronenberg, F., Meitinger, T., Mewes, H.-W., Wichmann, H.-E., Weinberger, K. M., Adamski, J., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000282 · Cited by 737
Metabolic signatures of exercise in human plasma
Lewis, G. D., Farrell, L., Wood, M. J., Martinovic, M., Arany, Z., Rowe, G. C., Souza, A., Cheng, S., McCabe, E. L., Yang, E., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001006 · Cited by 432
Susceptibility of Human Metabolic Phenotypes to Dietary Modulation
Stella, C., Beckwith-Hall, B., Cloarec, O., Holmes, E., Lindon, J. C., Powell, J., van der Ouderaa, F., Bingham, S., Cross, A. J., & Nicholson, J. K. (2006) · Journal of Proteome Research · doi:10.1021/pr060265y · Cited by 376
Self-citationHeinzmann, S. S., Brown, I. J., Chan, Q., Bictash, M., Dumas, M.-E., Kochhar, S., Stamler, J., Holmes, E., Elliott, P., & Nicholson, J. K. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29672 · Cited by 271
Self-citationThe Metabolome-Wide Association Study: a new look at human disease risk factors
Nicholson, J. K., Holmes, E., & Elliott, P. (2008) · Journal of Proteome Research · doi:10.1021/pr8005099 · Cited by 93
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Metabolomics: the apogee of the omics trilogy
Patti, G. J., Yanes, O., & Siuzdak, G. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3314 · Cited by 2,571
An atlas of genetic influences on human blood metabolites
The Multiple Tissue Human Expression Resource (MuTHER) Consortium, Shin, S.-Y., Fauman, E. B., Petersen, A.-K., Krumsiek, J., Santos, R., Huang, J., Arnold, M., Erte, I., Forgetta, V., et al. (2014) · Nature Genetics · doi:10.1038/ng.2982 · Cited by 1,515
Self-citationDona, A. C., Jiménez, B., Schäfer, H., Humpfer, E., Spraul, M., Lewis, M. R., Pearce, J. T. M., Holmes, E., Lindon, J. C., & Nicholson, J. K. (2014) · Analytical Chemistry · doi:10.1021/ac5025039 · Cited by 540
Self-citationLinear mixed-effects modeling approach to FMRI group analysis
Chen, G., Saad, Z. S., Britton, J. C., Pine, D. S., & Cox, R. W. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.01.047 · Cited by 447
The continuing value of twin studies in the omics era
van Dongen, J., Slagboom, P. E., Draisma, H. H. M., Martin, N. G., & Boomsma, D. I. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3243 · Cited by 373
Metadata
- Authors
- Nicholson, G., Rantalainen, M., Maher, A. D., Li, J. V., Malmodin, D., Ahmadi, K. R., Faber, J. H., Hallgrímsdóttir, I. B., Barrett, A., Toft, H., Krestyaninova, M., Viksna, J., Neogi, S. G., Dumas, M., Sarkans, U., The MolPAGE Consortium, Silverman, B. W., Donnelly, P., Nicholson, J. K., Allen, M., Zondervan, K. T., Lindon, J. C., Spector, T. D., McCarthy, M. I., Holmes, E., Baunsgaard, D., & Holmes, C. C.
- Venue
- Molecular Systems Biology
- Published
- 2011-01
- Volume
- 7
- Issue
- 1
- Pages
- 525-525
- ISSN
- 1744-4292 (ISSN-L)
- OpenAlex
- W2141034208
- Cited by
- 176
- References
- 9
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- gold
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