Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-07-06

AUTHORS

Xiaojing Chu, Martin Jaeger, Joep Beumer, Olivier B. Bakker, Raul Aguirre-Gamboa, Marije Oosting, Sanne P. Smeekens, Simone Moorlag, Vera P. Mourits, Valerie A. C. M. Koeken, Charlotte de Bree, Trees Jansen, Ian T. Mathews, Khoi Dao, Mahan Najhawan, Jeramie D. Watrous, Irma Joosten, Sonia Sharma, Hans J. P. M. Koenen, Sebo Withoff, Iris H. Jonkers, Romana T. Netea-Maier, Ramnik J. Xavier, Lude Franke, Cheng-Jian Xu, Leo A. B. Joosten, Serena Sanna, Mohit Jain, Vinod Kumar, Hans Clevers, Cisca Wijmenga, Mihai G. Netea, Yang Li

ABSTRACT

BackgroundRecent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.ResultWe systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target.ConclusionThis study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets. More... »

PAGES

198

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  • Journal

    TITLE

    Genome Biology

    ISSUE

    1

    VOLUME

    22

    Author Affiliations

  • TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
  • Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525, Nijmegen, HP, the Netherlands
  • Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, 3584, Utrecht, CT, the Netherlands
  • Department of Genetics, University of Groningen, University Medical Center Groningen, 9700, Groningen, RB, the Netherlands
  • La Jolla Institute, La Jolla, CA, USA
  • Departments of Medicine and Pharmacology, University of California, San Diego, CA, USA
  • Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525, Nijmegen, GA, the Netherlands
  • Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525, Nijmegen, HP, the Netherlands
  • Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, 02114, Boston, MA, USA
  • Oncode Institute, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, Utrecht, CS, the Netherlands
  • Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0372, Oslo, Norway
  • Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115, Bonn, Germany
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-021-02413-z

    DOI

    http://dx.doi.org/10.1186/s13059-021-02413-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1139414733

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34229738


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