Human metabolic individuality in biomedical and pharmaceutical research

Karsten Suhre (), So-Youn Shin, Ann-Kristin Petersen, Robert P. Mohney, David Meredith, Brigitte Wägele, Elisabeth Altmaier, Panos Deloukas, Jeanette Erdmann, Elin Grundberg, Christopher J. Hammond, Martin Hrabé de Angelis, Gabi Kastenmüller, Anna Köttgen, Florian Kronenberg, Massimo Mangino, Christa Meisinger, Thomas Meitinger, Hans-Werner Mewes, Michael V. Milburn, Cornelia Prehn, Johannes Raffler, Janina S. Ried, Werner Römisch-Margl, Nilesh J. Samani, Kerrin S. Small, H. -Erich Wichmann, Guangju Zhai, Thomas Illig, Tim D. Spector, Jerzy Adamski, Nicole Soranzo () and Christian Gieger
Additional contact information
Karsten Suhre: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
So-Youn Shin: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
Ann-Kristin Petersen: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Robert P. Mohney: Metabolon Inc., Durham, PO Box 110407, Research Triangle Park
David Meredith: School of Life Sciences, Oxford Brookes University, Gipsy Lane, Headington
Brigitte Wägele: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Elisabeth Altmaier: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Panos Deloukas: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
Jeanette Erdmann: Universität zu Lübeck, Medizinische Klinik II, Ratzeburger Allee 160
Elin Grundberg: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
Christopher J. Hammond: King’s College London, St Thomas' Hospital Campus, 1st Floor South Wing Block, 4 Westminster Bridge Road
Martin Hrabé de Angelis: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Gabi Kastenmüller: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Anna Köttgen: University Hospital Freiburg, Breisacherstrasse 66
Florian Kronenberg: Molecular and Clinical Pharmacology, Innsbruck Medical University, Christoph Probst Platz 1
Massimo Mangino: King’s College London, St Thomas' Hospital Campus, 1st Floor South Wing Block, 4 Westminster Bridge Road
Christa Meisinger: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Thomas Meitinger: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Hans-Werner Mewes: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Michael V. Milburn: Metabolon Inc., Durham, PO Box 110407, Research Triangle Park
Cornelia Prehn: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Johannes Raffler: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Janina S. Ried: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Werner Römisch-Margl: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Nilesh J. Samani: University of Leicester and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, University Road
Kerrin S. Small: King’s College London, St Thomas' Hospital Campus, 1st Floor South Wing Block, 4 Westminster Bridge Road
H. -Erich Wichmann: Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Guangju Zhai: King’s College London, St Thomas' Hospital Campus, 1st Floor South Wing Block, 4 Westminster Bridge Road
Thomas Illig: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Tim D. Spector: King’s College London, St Thomas' Hospital Campus, 1st Floor South Wing Block, 4 Westminster Bridge Road
Jerzy Adamski: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
Nicole Soranzo: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
Christian Gieger: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1

Nature, 2011, vol. 477, issue 7362, 54-60

Abstract: Abstract Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10–60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn’s disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

Date: 2011
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DOI: 10.1038/nature10354

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