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Genome-wide association analyses highlight the role of the intestinal molecular environment in human gut microbiota variation.

Title: Genome-wide association analyses highlight the role of the intestinal molecular environment in human gut microbiota variation.
Authors: Dekkers, Koen F; Pertiwi, Kamalita; Baldanzi, Gabriel; Lundmark, Per; Hammar, Ulf; Moksnes, Marta Riise; Coward, Eivind; Nethander, Maria; Salih, Ghassan Ali; Miari, Mariam; Nguyen, Diem; Sayols-Baixeras, Sergi; Eklund, Aron C; Holm, Jacob Bak; Nielsen, H Bjørn; Volpiano, Camila Gazolla; Méric, Guillaume; Thangam, Manonanthini; Hakaste, Liisa; Tuomi, Tiinamaija; Ahlqvist, Emma; Smith, Christopher A; Allen, Marie; Reimann, Frank; Gribble, Fiona M; Ohlsson, Claes; Hveem, Kristian; Melander, Olle; Nilsson, Peter M; Engström, Gunnar; Smith, J Gustav; Michaëlsson, Karl; Ärnlöv, Johan; Orho-Melander, Marju; Fall, Tove
Publisher Information: Högskolan Dalarna, Medicinsk vetenskap; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg; Department of Public Health and Nursing, HUNT Center for Molecular and Clinical Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway, NO.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq, IQ.; Department of Clinical Sciences in Malmö, Lund University, Malmö; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala; Department of Surgical Sciences, Medical Epidemiology, Uppsala University, Uppsala; CIBER Cardiovascular diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain, ES.; Cmbio, Copenhagen, Denmark, DK.; Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia, AU., Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia, AU.; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala; Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia, AU.; Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia, AU.; Department of Cardiovascular Research, Translation, and Implementation, La Trobe University, Melbourne, Victoria, Australia, AU.; Department of Life Sciences, University of Bath, Bath, UK, GB.; Folkhälsan Research Center, Helsinki, Finland, FI.; Finnish Institute for Molecular Medicine (FIMM) and Research Program for Clinical and Molecular Medicine Diabetes and Obesity, Helsinki University, Helsinki, Finland, FI.; Department of Clinical Sciences in Malmö, Lund University, Malmö; Folkhälsan Research Center, Helsinki, Finland, FI.; Endocrinology, Abdominal Center, Helsinki University Central Hospital, Helsinki, Finland, FI.; Department of Clinical Sciences in Malmö, Lund University, Malmö; Finnish Institute for Molecular Medicine (FIMM) and Research Program for Clinical and Molecular Medicine Diabetes and Obesity, Helsinki University, Helsinki, Finland, FI.; Institute of Metabolic Science-Metabolic Research Laboratories & MRC-Metabolic Diseases Unit, University of Cambridge, Cambridge, UK, GB.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg; Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg; Department of Public Health and Nursing, HUNT Center for Molecular and Clinical Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway, NO.; HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway, NO.; Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway, NO.; Department of Clinical Sciences in Malmö, Lund University, Malmö; Department of Internal Medicine, Skåne University Hospital, Malmö; Department of Surgical Sciences, Medical Epidemiology, Uppsala University, Uppsala; Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Huddinge; Center of Clinical Research, Region Dalarna, Falun; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala; Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala; The Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and Science for Life Laboratory, Gothenburg; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg; Department of Cardiology, Clinical Sciences, Wallenberg Center for Molecular Medicine and Lund University Diabetes Center, Lund University, Lund; Department of Cardiology, Skåne University Hospital, Lund
Publication Year: 2026
Collection: Dalarna University: Publikationer
Subject Terms: Genetic association study; Microbiology; Epidemiology; Medical Genetics and Genomics; Medicinsk genetik och genomik; Gastroenterology and Hepatology; Gastroenterologi och hepatologi
Description: Despite the importance of the gut microbiome to health, the role of human genetic variation in shaping its composition remains poorly understood. Here we report genome-wide association analyses of harmonized metagenomic data from 16,017 adults in four Swedish population-based studies, with replication in 12,652 people from the Norwegian HUNT study. We identified variants in the OR51E1-OR51E2 locus, encoding sensors for microbiome-derived fatty acids, associated with microbial richness. We further identified 15 study-wide significant genetic associations (P < 5.4 × 10-11) involving eight loci and 14 common bacterial species, of which 11 associations at six loci were replicated. The results confirm previously reported associations at LCT, ABO and FUT2, and provide evidence for new loci MUC12, CORO7-HMOX2, SLC5A11, FOXP1 and FUT3-FUT6, with supporting data from metabolomics and gene expression analyses. Our findings link gut microbial variation genetically to gastrointestinal functions, including enteroendocrine fatty acid sensing, bile composition and mucosal layer composition.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: Nature Genetics, 1061-4036, 2026, 58:3, s. 540-549; PMID 41688638
DOI: 10.1038/s41588-026-02512-2
Availability: http://urn.kb.se/resolve?urn=urn:nbn:se:du-53017; https://doi.org/10.1038/s41588-026-02512-2
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.9429C73D
Database: BASE