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Opening up the “black box”: metabolic phenotyping and metabolome-wide association studies in epidemiology
Open accessAbstract
Background Metabolic phenotyping of humans allows information to be captured on the interactions between dietary, xenobiotic, other lifestyle and environmental exposures, and genetic variation, which together influence the balance between health and disease risks at both individual and population levels.Objectives We describe here the main procedures in large-scale metabolic phenotyping and their application to metabolome-wide association (MWA) studies.Methods By use of high-throughput technologies and advanced spectroscopic methods, application of metabolic profiling to large-scale epidemiologic sample collections, including metabolome-wide association (MWA) studies for biomarker discovery and identification.Discussion Metabolic profiling at epidemiologic scale requires optimization of experimental protocol to maximize reproducibility, sensitivity, and quantitative reliability, and to reduce analytical drift. Customized multivariate statistical modeling approaches are needed for effective data visualization and biomarker discovery with control for false-positive associations since 100s or 1,000s of complex metabolic spectra are being processed.Conclusion Metabolic profiling is an exciting addition to the armamentarium of the epidemiologist for the discovery of new disease-risk biomarkers and diagnostics, and to provide novel insights into etiology, biological mechanisms, and pathways.
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“MWASs have been proposed as useful tools for discovering low-molecular-weight biomarkers that are predictive of either causal exposures or disease progression (59, 165, 166).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [166]
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“The investigators showed that metabolite concentrations differed substantially between Asian and Western populations, suggesting important effects of diet and related risk factors, including the microbiota, on the risk of coronary artery disease and stroke.”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [166]
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“biomarkers were identified, namely alanine, which was directly correlated with blood pressure, and formate and hippurate, both of which were inversely correlated with blood pressure.”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [166]
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“The investigators showed that metabolite concentrations differed substantially between Asian and Western populations, suggesting important effects of diet and related risk factors, including the microbiota, on the risk of coronary artery disease and stroke.”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [166]
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Citations
Cites
Kohonen, T. (1990) · Neurocomputing · doi:10.1016/s0925-2312(98)00030-7 · Cited by 10,686
Kohonen, T. (1990) · Proceedings of the IEEE · doi:10.1109/5.58325 · Cited by 8,414
Smith, C. A., Want, E. J., O’Maille, G., Abagyan, R. A., & Siuzdak, G. E. (2006) · Analytical Chemistry · doi:10.1021/ac051437y · Cited by 5,296
Nicholson, J. K., Lindon, J. C., & Holmes, E. C. (1999) · Xenobiotica · doi:10.1080/004982599238047 · Cited by 3,991
Anderson, E. N. (1977) · eScholarship (California Digital Library) · Cited by 2,567
Orthogonal projections to latent structures (O‐PLS)
Trygg, J., & Wold, S. (2002) · Journal of Chemometrics · doi:10.1002/cem.695 · Cited by 2,523
Metabolite profiling for plant functional genomics
Fiehn, O., Kopka, J., Dörmann, P., Altmann, T., Trethewey, R. N., & Willmitzer, L. (2000) · Nature Biotechnology · doi:10.1038/81137 · Cited by 2,129
Nicholson, J. K., & Lindon, J. C. (2008) · Nature · doi:10.1038/4551054a · Cited by 1,931
Metabonomics: a platform for studying drug toxicity and gene function
Nicholson, J. K., Connelly, J. C., Lindon, J. C., & Holmes, E. C. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd728 · Cited by 1,915
The Generalization of Student's Ratio
Hotelling, H. (1931) · The Annals of Mathematical Statistics · doi:10.1214/aoms/1177732979 · Cited by 1,561
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-citationElliott, P., Peakman, T. C., & Biobank, O. B. O. U. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dym276 · Cited by 1,004
Cloarec, O., Dumas, M., Craig, A., Barton, R. H., Trygg, J., Hudson, J., Blancher, C., Gauguier, D., Lindon, J. C., Holmes, E. C., et al. (2005) · Analytical Chemistry · doi:10.1021/ac048630x · Cited by 912
Targeted Profiling: Quantitative Analysis of 1 H NMR Metabolomics Data
Weljie, A. M., Newton, J., Mercier, P., Carlson, E., & Slupsky, C. M. (2006) · Analytical Chemistry · doi:10.1021/ac060209g · Cited by 902
MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data
Katajamaa, M., Miettinen, J., & Orešič, M. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btk039 · Cited by 868
Metabolic Phenotyping in Health and Disease
Holmes, E. C., Wilson, I. D., & Nicholson, J. K. (2008) · Cell · doi:10.1016/j.cell.2008.08.026 · Cited by 846
Pharmaco-metabonomic phenotyping and personalized drug treatment
Andrew Clayton, T., Lindon, J. C., Cloarec, O., Antti, H., Charuel, C., Hanton, G., Provost, J.-P., Le Net, J.-L., Baker, D., Walley, R. J., et al. (2006) · Nature · doi:10.1038/nature04648 · Cited by 824
Pe'er, I., Yelensky, R., Altshuler, D., & Daly, M. J. (2008) · Genetic Epidemiology · doi:10.1002/gepi.20303 · Cited by 783
Martens, H. A., & Martens, M. (2000) · Food Quality and Preference · doi:10.1016/s0950-3293(99)00039-7 · Cited by 726
High resolution proton magnetic resonance spectroscopy of biological fluids
Nicholson, J. K., & Wilson, I. D. (1989) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/0079-6565(89)80008-1 · Cited by 637
Sangster, T., Major, H. J., Plumb, R. S., Wilson, A., & Wilson, I. D. (2006) · The Analyst · doi:10.1039/b604498k · Cited by 565
Concentration Measurement by Proton NMR Using the ERETIC Method
Akoka, S., Barantin, L., & Trierweiler, M. (1999) · Analytical Chemistry · doi:10.1021/ac981422i · Cited by 520
Gika, H., Theodoridis, G. A., Wingate, J. E., & Wilson, I. D. (2007) · Journal of Proteome Research · doi:10.1021/pr070183p · Cited by 502
The Metabolomics Standards Initiative
MSI Board Members: (2007) · Nature Biotechnology · doi:10.1038/nbt0807-846b · Cited by 454
Slupsky, C. M., Rankin, K. N., Wagner, J., Fu, H., Chang, D., Weljie, A. M., Saude, E. J., Lix, B., Adamko, D. J., Shah, S. L., et al. (2007) · Analytical Chemistry · doi:10.1021/ac0708588 · Cited by 410
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
Presenting and exploring biological pathways with PathVisio
van Iersel, M., Kelder, T., Pico, A. R., Hanspers, K., Coort, S. L., Conklin, B. R., & Evelo, C. T. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-399 · Cited by 365
Dumas, M., Maibaum, E., Teague, C. R., Ueshima, H., Zhou, B., Lindon, J. C., Nicholson, J. K., Stamler, J., Elliott, P., Chan, Q. M., et al. (2006) · Analytical Chemistry · doi:10.1021/ac0517085 · Cited by 347
Crockford, D. J., Holmes, E. C., Lindon, J. C., Plumb, R. S., Zirah, S., Bruce, S. J., Rainville, P. D., Stumpf, C. L., & Nicholson, J. K. (2005) · Analytical Chemistry · doi:10.1021/ac051444m · Cited by 341
O2‐PLS, a two‐block (X–Y) latent variable regression (LVR) method with an integral OSC filter
Trygg, J., & Wold, S. (2003) · Journal of Chemometrics · doi:10.1002/cem.775 · Cited by 340
Gavaghan, C. L., Holmes, E. C., Lenz, E. M., Wilson, I. D., & Nicholson, J. K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02147-5 · Cited by 321
INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary)
Stamler, J., Elliott, P., Dennis, B., Dyer, A., Kesteloot, H., Liu, K., Ueshima, H., & Zhou, B. (2003) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1001603 · Cited by 279
Lewis, I. A., Schommer, S. C., Hodis, B., Robb, K., Tonelli, M., Westler, W. M., Sussman, M. R., & Markley, J. L. (2007) · Analytical Chemistry · doi:10.1021/ac071583z · Cited by 278
Biological sample collection and processing for molecular epidemiological studies
Holland, N., Smith, M. T., Eskenazi, B., & Bastaki, M. (2003) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(02)00090-x · Cited by 278
Summary recommendations for standardization and reporting of metabolic analyses
The Standard Metabolic Reporting Structures working group (2005) · Nature Biotechnology · doi:10.1038/nbt0705-833 · Cited by 277
MET-IDEA: Data Extraction Tool for Mass Spectrometry-Based Metabolomics
Broeckling, C. D., Reddy, I. R., Duran, A. L., Zhao, X., & Sumner, L. W. (2006) · Analytical Chemistry · doi:10.1021/ac0521596 · Cited by 275
Evidence of different metabolic phenotypes in humans
Assfalg, M., Bertini, I., Colangiuli, D., Luchinat, C., Schäfer, H., Schütz, B., & Spraul, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705685105 · Cited by 256
Robertson, D. G. (2000) · Toxicological Sciences · doi:10.1093/toxsci/57.2.326 · Cited by 255
The Expanding Role of Mass Spectrometry in Metabolite Profiling and Characterization
Want, E. J., Cravatt, B. F., & Siuzdak, G. E. (2005) · ChemBioChem · doi:10.1002/cbic.200500151 · Cited by 250
Lenz, E. M., Bright, J. D., Wilson, I. D., Hughes, A. M., Morrisson, J., Lindberg, H., & Lockton, A. (2004) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2004.08.002 · Cited by 248
Analytical Reproducibility in 1H NMR-Based Metabonomic Urinalysis
Keun, H. C., Ebbels, T. M. D., Antti, H., Bollard, M. E., Beckonert, O. P., Schlotterbeck, G., Senn, H., Niederhauser, U., Holmes, E. C., Lindon, J. C., et al. (2002) · Chemical Research in Toxicology · doi:10.1021/tx0255774 · Cited by 247
Impact of Analytical Bias in Metabonomic Studies of Human Blood Serum and Plasma
Teahan, O., Gamble, S. C., Holmes, E. C., Waxman, J., Nicholson, J. K., Bevan, C. L., & Keun, H. C. (2006) · Analytical Chemistry · doi:10.1021/ac051972y · Cited by 242
A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects
Lenz, E. M., Bright, J. D., Wilson, I. D., Morgan, S. R., & Nash, A. (2003) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/s0731-7085(03)00410-2 · Cited by 241
Kochhar, S., Jacobs, D. M., Ramadan, Z., Berruex, F., Fuerholz, A., & Fay, L. B. (2006) · Analytical Biochemistry · doi:10.1016/j.ab.2006.02.033 · Cited by 222
Lauridsen, M. B., Hansen, S. H., Jaroszewski, J. W., & Cornett, C. (2007) · Analytical Chemistry · doi:10.1021/ac061354x · Cited by 179
Holmes, E. C., Bonner, F. W., Sweatman, B. C., Lindon, J. C., Beddell, C. R., Rahr, E., & Nicholson, J. K. (1992) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09200-4 · Cited by 170
Gartland, K. P. R., Beddell, C. R., Lindon, J. C., & Nicholson, J. K. (1991) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)11071-7 · Cited by 168
Human Metabolic Phenotypes Link Directly to Specific Dietary Preferences in Healthy Individuals
Rezzi, S., Ramadan, Z., Martin, F., Fay, L. B., van Bladeren, P., Lindon, J. C., Nicholson, J. K., & Kochhar, S. (2007) · Journal of Proteome Research · doi:10.1021/pr070431h · Cited by 165
MathDAMP: a package for differential analysis of metabolite profiles
Baran, R., Kochi, H., Saito, N., Suematsu, M., Soga, T., Nishioka, T., Robert, M., & Tomita, M. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-530 · Cited by 162
The UK Biobank sample handling and storage validation studies
Peakman, T. C., & Elliott, P. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dyn019 · Cited by 162
Gender‐related and age‐related urinalysis of healthy subjects by NMR‐based metabonomics
Psihogios, N. G., Gazi, I., Elisaf, M., Seferiadis, K., & Bairaktari, E. (2008) · NMR in Biomedicine · doi:10.1002/nbm.1176 · Cited by 161
Rantalainen, M., Cloarec, O., Beckonert, O. P., Wilson, I. D., Jackson, D. P., Tonge, R., Rowlinson, R. A., Rayner, S., Nickson, J. A., Wilkinson, R. W., et al. (2006) · Journal of Proteome Research · doi:10.1021/pr060124w · Cited by 150
Bruce, S. J., Jonsson, P., Antti, H., Cloarec, O., Trygg, J., Marklund, S. L., & Möritz, T. (2007) · Analytical Biochemistry · doi:10.1016/j.ab.2007.09.037 · Cited by 143
Dunn, W. B., Broadhurst, D., Ellis, D. I., Brown, M., Halsall, A., O’Hagan, S., Spasić, ., Tseng, A., & Kell, D. B. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dym281 · Cited by 140
Craig, A., Sidaway, J. E., Holmes, E. C., Orton, T. C., Jackson, D., Rowlinson, R. A., Nickson, J. A., Tonge, R., Wilson, I. D., & Nicholson, J. K. (2006) · Journal of Proteome Research · doi:10.1021/pr0503376 · Cited by 135
Jonsson, P., Bruce, S. J., Möritz, T., Trygg, J., Sjöstróm, M., Plumb, R. S., Granger, J. H., Maibaum, E., Nicholson, J. K., Holmes, E. C., et al. (2005) · The Analyst · doi:10.1039/b501890k · Cited by 124
Barton, R., Nicholson, J., Elliott, P., & Holmes, E. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dym284 · Cited by 124
Maher, A. D., Zirah, S., Holmes, E. C., & Nicholson, J. K. (2007) · Analytical Chemistry · doi:10.1021/ac070212f · Cited by 112
Griffin, J. L., Bonney, S. A., Mann, C., Hebbachi, A. M., Gibbons, G. F., Nicholson, J. K., Shoulders, C. C., & Scott, J. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00158.2003 · Cited by 103
Estimation and control of multiple testing error rates for microarray studies
Pounds, S. B. (2006) · Briefings in Bioinformatics · doi:10.1093/bib/bbk002 · Cited by 102
Klenø, T. G., Kiehr, B., Baunsgaard, D., & Sidelmann, U. G. (2004) · Biomarkers · doi:10.1080/13547500410001728408 · Cited by 92
Wagner, S., Scholz, K., Sieber, M., Kellert, M., & Völkel, W. (2007) · Analytical Chemistry · doi:10.1021/ac062153w · Cited by 91
A critical evaluation of the application of biomarkers in epidemiological studies on diet and health
Wild, C. P., Andersson, C., O’Brien, N. M., Wilson, L., & Woods, J. A. (2001) · British Journal Of Nutrition · doi:10.1079/bjn2001338 · Cited by 82
Crockford, D. J., Keun, H. C., Smith, L. M., Holmes, E. C., & Nicholson, J. K. (2005) · Analytical Chemistry · doi:10.1021/ac0503456 · Cited by 81
Pasikanti, K. K., Ho, P. C., & Chan, E. C. Y. (2008) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.3699 · Cited by 72
Molecular epidemiology biomarkers—Sample collection and processing considerations
Holland, N., Pfleger, L., Berger, E., Ho, A., & Bastaki, M. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.10.024 · Cited by 65
Metabolic Phenotyping of Nude and Normal (Alpk:ApfCD, C57BL10J) Mice
McKee, C. L. G., Wilson, I. D., & Nicholson, J. K. (2006) · Journal of Proteome Research · doi:10.1021/pr050255h · Cited by 62
Elliott, P., & Stamler, R. (1988) · PubMed · Cited by 61
Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome
Vilasi, A., Cutillas, P. R., Maher, A. D., Zirah, S., Capasso, G., Norden, A. W. G., Holmes, E. C., Nicholson, J. K., & Unwin, R. J. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00095.2007 · Cited by 59
Sodium, potassium, body mass, alcohol and blood pressure
&NA;, &. (1988) · Journal of Hypertension · doi:10.1097/00004872-198812040-00183 · Cited by 35
Defining Personal Nutrition and Metabolic Health Through Metabonomics
Rezzi, S., Martin, F., & Kochhar, S. (2008) · Ernst Schering Research Foundation workshop/Ernst Schering Foundation Symposium proceedings · doi:10.1007/2789_2008_097 · Cited by 19
P119-M Combined Analysis of Urine Samples using NMR and LC/MS
Zurek, G., Godejohann, M., Schäfer, H., Fischer, C., Neidig, P., Han, D., Lee, E., & Spraul, M. (2007) · PubMed Central · Cited by 1
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Metadata
- Authors
- Bictash, M., Ebbels, T. M., Chan, Q., Loo, R. L., Yap, I. K. S., Brown, I. J., de Iorio, M., Daviglus, M. L., Holmes, E., Stamler, J., Nicholson, J. K., & Elliott, P.
- Affiliations
- Imperial College London (GB)
- Medway School of Pharmacy (GB)
- Northwestern University (US)
- Corresponding author
- Nicholson, Jeremy K.
- Elliott, Paul
- ORCID
- Venue
- Journal of Clinical Epidemiology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 63
- Issue
- 9
- Pages
- 970-979
- ISSN
- 0895-4356 (ISSN-L)
- PMC
- PMC4048926
- OpenAlex
- W2130686160
- Cited by
- 140
- References
- 74
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 6 · 2019: 12 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 11 · 2013: 11 · 2012: 15
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Murdoch University Research Portal (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- National Heart, Lung, and Blood Institute (090357003)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- metabolic phenotyping, metabolome-wide association study, metabolite profiling, biomarker discovery, high-throughput metabolomics, false positive association, multivariate statistical modeling, genetic variation
- MeSH terms
- Humans, Phenotype, Reproducibility of Results, Biomarkers, Molecular Epidemiology, Risk Assessment, Metabolomics, Metabolome
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