Large-scale association analyses identify host factors influencing human gut microbiome composition View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-01-18

AUTHORS

Alexander Kurilshikov, Carolina Medina-Gomez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayse Demirkan, Caroline I. Le Roy, Juan Antonio Raygoza Garay, Casey T. Finnicum, Xingrong Liu, Daria V. Zhernakova, Marc Jan Bonder, Tue H. Hansen, Fabian Frost, Malte C. Rühlemann, Williams Turpin, Jee-Young Moon, Han-Na Kim, Kreete Lüll, Elad Barkan, Shiraz A. Shah, Myriam Fornage, Joanna Szopinska-Tokov, Zachary D. Wallen, Dmitrii Borisevich, Lars Agreus, Anna Andreasson, Corinna Bang, Larbi Bedrani, Jordana T. Bell, Hans Bisgaard, Michael Boehnke, Dorret I. Boomsma, Robert D. Burk, Annique Claringbould, Kenneth Croitoru, Gareth E. Davies, Cornelia M. van Duijn, Liesbeth Duijts, Gwen Falony, Jingyuan Fu, Adriaan van der Graaf, Torben Hansen, Georg Homuth, David A. Hughes, Richard G. Ijzerman, Matthew A. Jackson, Vincent W. V. Jaddoe, Marie Joossens, Torben Jørgensen, Daniel Keszthelyi, Rob Knight, Markku Laakso, Matthias Laudes, Lenore J. Launer, Wolfgang Lieb, Aldons J. Lusis, Ad A. M. Masclee, Henriette A. Moll, Zlatan Mujagic, Qi Qibin, Daphna Rothschild, Hocheol Shin, Søren J. Sørensen, Claire J. Steves, Jonathan Thorsen, Nicholas J. Timpson, Raul Y. Tito, Sara Vieira-Silva, Uwe Völker, Henry Völzke, Urmo Võsa, Kaitlin H. Wade, Susanna Walter, Kyoko Watanabe, Stefan Weiss, Frank U. Weiss, Omer Weissbrod, Harm-Jan Westra, Gonneke Willemsen, Haydeh Payami, Daisy M. A. E. Jonkers, Alejandro Arias Vasquez, Eco J. C. de Geus, Katie A. Meyer, Jakob Stokholm, Eran Segal, Elin Org, Cisca Wijmenga, Hyung-Lae Kim, Robert C. Kaplan, Tim D. Spector, Andre G. Uitterlinden, Fernando Rivadeneira, Andre Franke, Markus M. Lerch, Lude Franke, Serena Sanna, Mauro D’Amato, Oluf Pedersen, Andrew D. Paterson, Robert Kraaij, Jeroen Raes, Alexandra Zhernakova

ABSTRACT

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. More... »

PAGES

156-165

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    2

    VOLUME

    53

    Author Affiliations

  • Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
  • The Generation R Study, Erasmus MC University Medical Center, Rotterdam, the Netherlands
  • Center for Microbiology, VIB, Leuven, Belgium
  • Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
  • Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
  • Section of Statistical Multi-Omics, Department of Clinical & Experimental Medicine, School of Biosciences & Medicine, University of Surrey, Guildford, UK
  • Department of Twin Research & Genetic Epidemiology, King’s College London, London, UK
  • Division of Gastroenterology, Mount Sinai Hospital, Toronto, Ontario, Canada
  • Avera Institute of Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, SD, USA
  • Center for Molecular Medicine and Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  • Laboratory of Genomic Diversity, Center for Computer Technologies, ITMO University, St. Petersburg, Russia
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
  • Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
  • Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
  • Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
  • Department of Computer Science and Cell Biology, Weizmann Institute of Science, Rehovot, Israel
  • COPSAC, Copenhagen University Hospital, Copenhagen, Denmark
  • Human Genetics Center School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
  • Department of Psychiatry, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands
  • Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA
  • Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
  • Stress Research Institute, Stockholm University, Stockholm, Sweden
  • Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
  • Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands
  • Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
  • Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
  • Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
  • Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
  • Population Health Sciences, Bristol Medical School, Bristol, UK
  • Department of Endocrinology, Amsterdam University Medical Center, location VUMC, Amsterdam, the Netherlands
  • Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
  • Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
  • Centre for Clinical Research and Prevention, Bispebjerg/Frederiksberg Hospital, Capital Region of Copenhagen and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
  • Center for Microbiome Innovation and Department of Bioengeering, University of California, San Diego, La Jolla, CA, USA
  • Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
  • Department of Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
  • Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, MD, USA
  • Institute of Epidemiology, Kiel University, Kiel, Germany
  • Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
  • Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • Department of Biology, University of Copenhagen, Copenhagen, Denmark
  • Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
  • Department of Gastroenterology, County Council of Östergötland, Linköping, Sweden
  • Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, the Netherlands
  • School of Public Health, Harvard University, Boston, MA, USA
  • Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands
  • Amsterdam Public Health, Amsterdam UMC, Amsterdam, the Netherlands
  • Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA
  • Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Republic of Korea
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • Istituto di Ricerca Genetica e Biomedica, National Research Council, Monserrato, Italy
  • Ikerbasque, Basque Science Foundation, Bilbao, Spain
  • Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-020-00763-1

    DOI

    http://dx.doi.org/10.1038/s41588-020-00763-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1134663791

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33462485


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