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On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies

Ann-Kristin Petersen, Jan Krumsiek, Brigitte Wägele, Fabian J Theis, H-Erich Wichmann, Christian Gieger, Karsten Suhre
2012 BMC Bioinformatics  
Hypothesis-free testing of ratios between all possible metabolite pairs in GWAS and MWAS has proven to be an innovative approach in the discovery of new biologically meaningful associations.  ...  Genome-wide association studies (GWAS) with metabolic traits and metabolome-wide association studies (MWAS) with traits of biomedical relevance are powerful tools to identify the contribution of genetic  ...  Part of this work was financed by the German National Genome Research Network (NGFN-2, NGFNPlus 01GS0823, and NGFNPlus 01GS0834) and through additional funds from the University of Ulm.  ... 
doi:10.1186/1471-2105-13-120 pmid:22672667 pmcid:PMC3537592 fatcat:awcnopbk7ffgnib4h2rawesyau

Metabolomics in epidemiology: from metabolite concentrations to integrative reaction networks

Liam G Fearnley, Michael Inouye
2016 International Journal of Epidemiology  
now allow generation of population-scale metabolomics and other 'omics' data. • Parallel advances in computational and statistical approaches enable the integration of these data. • Consequently, analytical  ...  Metabolomics is becoming feasible for population-scale studies of human disease.  ...  These 'genome-scale' models of metabolism are widely used in the bioengineering and systems biology communities as a tool for computational hypothesis generation and testing. 97 They are derived from  ... 
doi:10.1093/ije/dyw046 pmid:27118561 pmcid:PMC5100607 fatcat:ql53omilqjeozby3mlsdkcgduu

A genome-wide perspective of genetic variation in human metabolism

Thomas Illig, Christian Gieger, Guangju Zhai, Werner Römisch-Margl, Rui Wang-Sattler, Cornelia Prehn, Elisabeth Altmaier, Gabi Kastenmüller, Bernet S Kato, Hans-Werner Mewes, Thomas Meitinger, Martin Hrabé de Angelis (+6 others)
2009 Nature Genetics  
7 for metabolite concentrations and <10 −9 for concentration ratios in a genome-wide association screen ( Fig. 1) . 32 loci satisfy these criteria.  ...  For the purpose of the replication for the KORA study, the data on the metabolites, the ratios of the concentration, and the genotypes were extracted from the available database, and the association between  ... 
doi:10.1038/ng.507 pmid:20037589 pmcid:PMC3773904 fatcat:pe4p4pzkhrawrjqnpqaky3jiye

Look, no hands! Spectral biomarkers from genetic association studies

Michael Inouye, Gad Abraham
2013 Genome Medicine  
Acknowledgements MI is supported by the NHMRC (fellowship no. 637400). Published: 15 February 2013  ...  Analogously, the new study [7] shows the benefi t of considering phenotypes in an Abstract Recent advances in our understanding of the genomics of the human metabolome have shed light on the pathways  ...  Instead of searching for previously characterized metabolites in the NMR spectra and testing for association of these metabolites with geno type, the authors examined all available signals in the molecular  ... 
doi:10.1186/gm418 pmid:23510086 pmcid:PMC3706812 fatcat:ydilorhifzaalcqji3xnqixq2e

metaP-Server: A Web-Based Metabolomics Data Analysis Tool

Gabi Kastenmüller, Werner Römisch-Margl, Brigitte Wägele, Elisabeth Altmaier, Karsten Suhre
2011 Journal of Biomedicine and Biotechnology  
Due to recent technical advances, metabolomics can now be used widely as an analytical high-throughput technology in drug testing and epidemiological metabolome and genome wide association studies.  ...  Metabolomics is an emerging field that is based on the quantitative measurement of as many small organic molecules occurring in a biological sample as possible.  ...  Acknowledgments The authors thank Jerzy Adamski and Cornelia Prehn from the Genome Analysis Center  ... 
doi:10.1155/2011/839862 pmid:20936179 pmcid:PMC2946609 fatcat:t5ikmbcm2jgotbofituou5ijq4

Genome-wide association study identifies multiple loci influencing human serum metabolite levels

Johannes Kettunen, Taru Tukiainen, Antti-Pekka Sarin, Alfredo Ortega-Alonso, Emmi Tikkanen, Leo-Pekka Lyytikäinen, Antti J Kangas, Pasi Soininen, Peter Würtz, Kaisa Silander, Danielle M Dick, Richard J Rose (+19 others)
2012 Nature Genetics  
We thank the IT Center for Science and the technology center of the Institute for Molecular Medicine Finland for providing the computational facilities required in this study.  ...  Acknowledgments We thank all the Finnish volunteers who participated in the studies.  ...  In our study, the same locus was associated with the LA/PUFA ratio, with linoleic acid being one of the metabolites involved in eicosanoid synthesis.  ... 
doi:10.1038/ng.1073 pmid:22286219 pmcid:PMC3605033 fatcat:j6xio6f5ovhsfeiek5fxrujnje

A description of large-scale metabolomics studies: increasing value by combining metabolomics with genome-wide SNP genotyping and transcriptional profiling

Georg Homuth, Alexander Teumer, Uwe Völker, Matthias Nauck
2012 Journal of Endocrinology  
Metabolic traits can be related to genetic polymorphisms in genome-wide association studies, enabling the identification of underlying genetic factors, as well as to specific phenotypes, resulting in the  ...  This review will therefore try to summarize the most important of these studies and give an outlook on future developments.  ...  Acknowledgements The authors are grateful to Michael Lalk for critical reading of the manuscript and his helpful comments.  ... 
doi:10.1530/joe-12-0144 pmid:22782382 fatcat:qc7muxmrjrhnlamv5vnfvrwciu

Integrated Metabolomics and Genomics

Svati H. Shah, Christopher B. Newgard
2015 Circulation: Cardiovascular Genetics  
showing the potential for such studies in deciphering cardiovascular disease genetics, biomarkers, and mechanisms.  ...  We review important studies that have used metabolomic profiling in cardiometabolic diseases, approaches for integrating metabolomics with genetics and other molecular profiling platforms, and key studies  ...  Sources of Funding Work cited in this article was supported by National Institutes of Health grants HL095987 (Shah) and P01-DK58398 (Newgard) and by a sponsored research agreement from Pfizer.  ... 
doi:10.1161/circgenetics.114.000223 pmid:25901039 pmcid:PMC4408557 fatcat:ubp6sysxhnekjlffcexdwydzku

Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum

Christian Gieger, Ludwig Geistlinger, Elisabeth Altmaier, Martin Hrabé de Angelis, Florian Kronenberg, Thomas Meitinger, Hans-Werner Mewes, H.-Erich Wichmann, Klaus M. Weinberger, Jerzy Adamski, Thomas Illig, Karsten Suhre (+1 others)
2008 PLoS Genetics  
To test this hypothesis, we conducted what is, to the best of our knowledge, the first GWA study with metabolomics based on the quantitative measurement of 363 metabolites in serum of 284 male participants  ...  The rapidly evolving field of metabolomics aims at a comprehensive measurement of ideally all endogenous metabolites in a cell or body fluid.  ...  and conduct of the MONICA/KORA Augsburg studies.  ... 
doi:10.1371/journal.pgen.1000282 pmid:19043545 pmcid:PMC2581785 fatcat:sqbhaojicvhufdvtx43wouhqzq

Effect of inbreeding on type 2 diabetes-related metabolites in a Dutch genetic isolate [article]

Ayşe Demirkan, Jun Liu, Najaf Amin, Ko Willems van Dijk, Cornelia M. van Duijn
2019 bioRxiv   pre-print
We calculated individual whole genome-based, exome-based and pedigree-based inbreeding coefficients and tested their influence on the T2DM-related metabolites as well as T2DM risk factors.  ...  We also performed model supervised genome-wide association analysis (GWAS) for the metabolites which significantly correlate with inbreeding values.  ...  Genome-wide association study (GWAS) of the candidate metabolites were performed 193 by using --all models and --mmscore functions as implemented in the ProbABEL software 194 (v.0.3.0), using 1000G imputation  ... 
doi:10.1101/618801 fatcat:3ydtcwtud5cydmhqwypeiqx56u

Beyond the Single SNP: Emerging Developments in Mendelian Randomization in the "Omics" Era

Marie-Jo A. Brion, Beben Benyamin, Peter M. Visscher, George Davey Smith
2014 Current Epidemiology Reports  
new-generation biological "omics" data (such as genome-wide genotype data, epigenetics, and metabolomic data).  ...  The explosion in availability of high-throughput biological data has resulted in increasing numbers of MR studies, novel extensions to the traditional single-SNP MR approach, and the potential to incorporate  ...  In this way, one could effectively test the causality of extremely large numbers of phenotypic associations in a single study.  ... 
doi:10.1007/s40471-014-0024-2 fatcat:jfjrjlszzbfwvha6ltweg5xoh4

Metabolomics: Basic Principles and Strategies [chapter]

Sinem Nalbantoglu
2019 Molecular Medicine [Working Title]  
Metabolomics has several applications in health and disease including precision/personalized medicine, single cell, epidemiologic population studies, metabolic phenotyping, and metabolome-wide association  ...  Metabolomics is the study of metabolome within cells, biofluids, tissues, or organisms to comprehensively identify and quantify all endogenous and exogenous low-molecular-weight (<1 kDa) small molecules  ...  9 Metabolomics: Basic Principles and Strategies DOI:  ... 
doi:10.5772/intechopen.88563 fatcat:gksen5bxbvacxcttwa7prisk4q

Integrated genomics and metabolomics in nephrology

D. Atzler, E. Schwedhelm, T. Zeller
2013 Nephrology, Dialysis and Transplantation  
Targeted analyses are applied in hypothesis-testing studies and focus on the detection and quantification of dozens to hundreds of characterized and annotated metabolites.  ...  A B S T R AC T Applying 'omics' approaches such as genome-wide association studies (GWAS) and metabolome analyses, genes and metabolites have been identified to be associated with renal pathophysiology  ... 
doi:10.1093/ndt/gft492 pmid:24366899 fatcat:awuttwvkmnadvhscwkslqlm32i

The Intestinal Metabolome: An Intersection Between Microbiota and Host

Luke K. Ursell, Henry J. Haiser, Will Van Treuren, Neha Garg, Lavanya Reddivari, Jairam Vanamala, Pieter C. Dorrestein, Peter J. Turnbaugh, Rob Knight
2014 Gastroenterology  
The authors disclose no conflicts.  ...  Wikoff et al 29 directly tested the effect of the gut microbiota on the host by comparing the plasma metabolomic profile, obtained via untargeted mass spectrometry, between germ-free and conventionally  ...  metabolomic analysis pipeline to correlate the presence of the microbial metabolite p-cresol with a reduction in the ratio of sulfonated to glucuronidated acetaminophen.  ... 
doi:10.1053/j.gastro.2014.03.001 pmid:24631493 pmcid:PMC4102302 fatcat:tz3eb4wbhvb4xduyi2uu775gyi

A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers

Jelle Vehof, Pirro G. Hysi, Christopher J. Hammond
2017 Ophthalmology (Rochester, Minn.)  
Purpose: To test the association between serum metabolites and dry eye disease (DED) using a hypothesisfree metabolomics approach. Design: Cross-sectional association study.  ...  Conclusions: This hypothesis-free metabolomic approach found decreased serum androgens to be highly associated with DED and adds important evidence to the growing body of research that links androgens  ...  Discussion In this hypothesis-free study, we have shown strong associations of DED with all 5 androgens included in this screen of 222 known metabolites.  ... 
doi:10.1016/j.ophtha.2016.12.011 pmid:28139245 pmcid:PMC5375174 fatcat:gxvabolopvh5bfph6ugpie2ucq
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