bioRxiv preprint doi: https://doi.org/10.1101/2020.06.26.173724; this version posted June 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Genetics of human gut microbiome composition Authors: Alexander Kurilshikov1,†, Carolina Medina-Gomez2,3,†, Rodrigo Bacigalupe4,5,†, Djawad Radjabzadeh2,†, Jun Wang4,5,6,†, Ayse Demirkan1,7§, Caroline I. Le Roy8,§, Juan Antonio 5 Raygoza Garay9,10,§, Casey T. Finnicum11,§, Xingrong Liu12,§, Daria V. Zhernakova1,§, Marc Jan Bonder1,§, Tue H. Hansen13, Fabian Frost14, Malte C. Rühlemann15, Williams Turpin9,10, Jee- Young Moon16, Han-Na Kim17,18, Kreete Lüll19, Elad Barkan20, Shiraz A. Shah21, Myriam Fornage22,23, Joanna Szopinska-Tokov24, Zachary D. Wallen25, Dmitrii Borisevich13, Lars Agreus26, Anna Andreasson27, Corinna Bang15, Larbi Bedrani9, Jordana T. Bell8, Hans 10 Bisgaard21, Michael Boehnke28, Dorret I. Boomsma29, Robert D. Burk16,30,31, Annique Claringbould1, Kenneth Croitoru9,10, Gareth E. Davies11,29, Cornelia M. van Duijn32,33, Liesbeth Duijts3,34, Gwen Falony4,5, Jingyuan Fu1,35, Adriaan van der Graaf1, Torben Hansen13, Georg Homuth36, David A. Hughes37,38, Richard G. Ijzerman39, Matthew A. Jackson7,40, Vincent W.V. Jaddoe3,32, Marie Joossens4,5, Torben Jørgensen41, Daniel Keszthelyi42,43, Rob Knight44,45,46, 15 Markku Laakso47, Matthias Laudes48, Lenore J. Launer49, Wolfgang Lieb50, Aldons J. Lusis51,52, Ad A.M. Masclee42,43, Henriette A. Moll34, Zlatan Mujagic42,43, Qi Qibin16, Daphna Rothschild20, Hocheol Shin53,54, Søren J. Sørensen55, Claire J. Steves8, Jonathan Thorsen21, Nicholas J. Timpson37,38, Raul Y. Tito4,5, Sara Vieira-Silva4,5, Uwe Völker36, Henry Völzke56, Urmo Võsa1, Kaitlin H. Wade37,38, Susanna Walter57,58, Kyoko Watanabe59, Stefan Weiss36, Frank U. Weiss14, 20 Omer Weissbrod60, Harm-Jan Westra1, Gonneke Willemsen29, Haydeh Payami25, Daisy M.A.E. Jonkers42,43, Alejandro Arias Vasquez24,61, Eco J.C. de Geus29,62, Katie A. Meyer63,64, Jakob Stokholm21, Eran Segal20, Elin Org19, Cisca Wijmenga1, Hyung-Lae Kim65, Robert C. Kaplan16,66, Tim D. Spector8, Andre G. Uitterlinden2,3,32, Fernando Rivadeneira2,3, Andre Franke15, Markus M. Lerch14, Lude Franke1, Serena Sanna1,67, Mauro D'Amato12,68,69,70, Oluf 25 Pedersen13, Andrew D. Paterson71, Robert Kraaij2,‡, Jeroen Raes4,5,‡, Alexandra Zhernakova1,‡,* Affiliations: 1Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands 2Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the 30 Netherlands 3The Generation R Study, Erasmus MC University Medical Center, Rotterdam, the Netherlands 4Department of Microbiology and Immunology, Rega Instituut, KU Leuven, Leuven, Belgium 5Center for Microbiology, VIB, Leuven, Belgium 6Institute of Microbiology, Chinese Academy of Sciences, Beijing, China 35 7Section of Statistical Multi-Omics, Department of Clinical & Experimental Medicine, School of Biosciences & Medicine, University of Surrey, Guildford, UK 8Department of Twin Research & Genetic Epidemiology, King's College London, London, UK 9Department of Medicine, University of Toronto, Toronto, Canada 10Division of Gastroenterology, Mount Sinai Hospital, Toronto, Canada 40 11Avera Institute of Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, USA 12Center for Molecular Medicine and Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.26.173724; this version posted June 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 13Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 14Department of Medicine A, University Medicine Greifswald, Greifswald, Germany 15Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany 5 16Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, USA 17Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 18Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, 10 Seoul, Republic of Korea 19Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia 20Department of Computer Science and Cell Biology, Weizmann Institute of Science, Rehovot, Israel 21COPSAC, Copenhagen University Hospital, Herlev-Gentofte, Copenhagen, Denmark 15 22Institute of Molecular Medicine McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA 23Human Genetics Center School of Public Health, The University of Texas Health Science Center at Houston, Houston, USA 24Department of Psychiatry, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, 20 Nijmegen, the Netherlands 25Department of Neurology, University of Alabama at Birmingham, Birmingham, USA 26Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden 27Stress Research Institute, Stockholm University, Stockholm, Sweden 25 28Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, USA 29Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands 30Department of Pediatrics, Albert Einstein College of Medicine, Bronx, USA 31Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, 30 USA 32Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands 33Nuffield Department of Population Health, University of Oxford, Oxford, UK 34Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, the Netherlands 35 35Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands 36Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany 37MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK 40 38Population Health Sciences, Bristol Medical School, Bristol, UK 39Department of Endocrinology, Amsterdam University Medical Center, location VUMC, Amsterdam, the Netherlands 40Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK 41Centre for Clinical Research and Disease Prevention, Bispebjerg/Frederiksberg Hospital, 45 Capital Region of Copenhagen and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 2 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.26.173724; this version posted June 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 42Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands 43NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands 5 44Department of Pediatrics, University of California San Diego, La Jolla, USA 45Center for Microbiome Innovation, University of California San Diego, La Jolla, USA 46Center for Microbiome Innovation and department of Bioengeering, University of California San Diego, La Jolla, USA 47Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 10 Finland 48Department of Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany 49Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, USA 15 50Institute of Epidemiology, Kiel University, Kiel, Germany 51Department of Human Genetics, University of California, Los Angeles, Los Angeles, USA 52Department of Medicine, University of California, Los Angeles, Los Angles, USA 53Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 20 54Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 55Department of Biology, University of Copenhagen, Copenhagen, Denmark 56Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany 57Department of Biomedical and Clinical Sciences, University of Linköping, Linköping, Sweden 25 58Department of gastroenterology, County Council of Östergötland, Linköping, Sweden 59Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, the Netherlands 60School of Public Health, Harvard University, Boston, USA 61Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition and 30 Behaviour, Nijmegen, the Netherlands 62Amsterdam Public Health, Amsterdam UMC, Amsterdam, the Netherlands 63Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, USA 64Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis,