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Human metabolic individuality in biomedical and pharmaceutical research

Author

Listed:
  • Karsten Suhre

    (Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
    Faculty of Biology, Ludwig-Maximilians-Universität, Großhaderner Str. 2
    Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO Box 24144)

  • 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
    Life and Food Science Center Weihenstephan, Technische Universität München, Alte Akademie 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
    King’s College London, St Thomas' Hospital Campus, 1st Floor South Wing Block, 4 Westminster Bridge Road)

  • 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
    Institute of Experimental Genetics, Life and Food Science Center Weihenstephan, Technische Universität München, Alte Akademie 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
    Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22)

  • Hans-Werner Mewes

    (Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1
    Life and Food Science Center Weihenstephan, Technische Universität München, Alte Akademie 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
    Faculty of Biology, Ludwig-Maximilians-Universität, Großhaderner Str. 2)

  • 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
    Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Geschwister-Scholl-Platz 1
    Klinikum Grosshadern, Marchioninistraße 15)

  • 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
    Institute of Experimental Genetics, Life and Food Science Center Weihenstephan, Technische Universität München, Alte Akademie 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)

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.

Suggested Citation

  • 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. Ham, 2011. "Human metabolic individuality in biomedical and pharmaceutical research," Nature, Nature, vol. 477(7362), pages 54-60, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7362:d:10.1038_nature10354
    DOI: 10.1038/nature10354
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    Cited by:

    1. Anna Halama & Shaza Zaghlool & Gaurav Thareja & Sara Kader & Wadha Al Muftah & Marjonneke Mook-Kanamori & Hina Sarwath & Yasmin Ali Mohamoud & Nisha Stephan & Sabine Ameling & Maja Pucic Baković & Jan, 2024. "A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Xianyong Yin & Lap Sum Chan & Debraj Bose & Anne U. Jackson & Peter VandeHaar & Adam E. Locke & Christian Fuchsberger & Heather M. Stringham & Ryan Welch & Ketian Yu & Lilian Fernandes Silva & Susan K, 2022. "Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Linda Ottensmann & Rubina Tabassum & Sanni E. Ruotsalainen & Mathias J. Gerl & Christian Klose & Elisabeth Widén & Kai Simons & Samuli Ripatti & Matti Pirinen, 2023. "Genome-wide association analysis of plasma lipidome identifies 495 genetic associations," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Usman A. Tahir & Daniel H. Katz & Julian Avila-Pachecho & Alexander G. Bick & Akhil Pampana & Jeremy M. Robbins & Zhi Yu & Zsu-Zsu Chen & Mark D. Benson & Daniel E. Cruz & Debby Ngo & Shuliang Deng & , 2022. "Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Elena V. Feofanova & Michael R. Brown & Taryn Alkis & Astrid M. Manuel & Xihao Li & Usman A. Tahir & Zilin Li & Kevin M. Mendez & Rachel S. Kelly & Qibin Qi & Han Chen & Martin G. Larson & Rozenn N. L, 2023. "Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Gemma Cadby & Corey Giles & Phillip E. Melton & Kevin Huynh & Natalie A. Mellett & Thy Duong & Anh Nguyen & Michelle Cinel & Alex Smith & Gavriel Olshansky & Tingting Wang & Marta Brozynska & Mike Ino, 2022. "Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Shaza B. Zaghlool & Anna Halama & Nisha Stephan & Valborg Gudmundsdottir & Vilmundur Gudnason & Lori L. Jennings & Manonanthini Thangam & Emma Ahlqvist & Rayaz A. Malik & Omar M. E. Albagha & Abdul Ba, 2022. "Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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