Genome-wide association analyses highlight the role of the intestinal molecular environment in human gut microbiota variation
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Nature Genetics
Authors: Koen F. Dekkers, Kamalita Pertiwi, Gabriel Baldanzi, Per Lundmark, Ulf Hammar, Marta Riise Moksnes, Eivind Coward, Maria Nethander, Ghassan Ali Salih, Mariam Miari, Diem Nguyen, Sergi Sayols-Baixeras, Aron C. Eklund, Jacob Bak Holm, H. Bjørn Nielsen, Camila Gazolla Volpiano, Guillaume Méric, Manonanthini Thangam, Liisa Hakaste, Tiinamaija Tuomi, Emma Ahlqvist, Christopher A. Smith, Marie Allen, Frank Reimann, Fiona M. Gribble, Claes Ohlsson, Kristian Hveem, Olle Melander, Peter M. Nilsson, Gunnar Engström, J. Gustav Smith, Karl Michaëlsson, Johan Ärnlöv, Marju Orho-Melander, Tove Fall
Institutions: Uppsala University, University of Gothenburg, Norwegian University of Science and Technology, University of Baghdad, Lund University, Instituto de Salud Carlos III, Centro de Investigación en Red en Enfermedades Cardiovasculares, Baker Heart and Diabetes Institute, The University of Melbourne, La Trobe University, University of Bath, University of Helsinki, Institute for Molecular Medicine Finland, Folkhälsans Forskningscentrum, Helsinki University Hospital, University of Cambridge, Wellcome/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit, Sahlgrenska University Hospital, Region Västra Götaland, Levanger Hospital, Helse Nord-Trøndelag HF, Skåne University Hospital, Science for Life Laboratory, Dalarna University, Karolinska Institutet, Center for Clinical Research Dalarna
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Helsingin Yliopisto, Norges Teknisk-Naturvitenskapelige Universitet, Finska Läkaresällskapet, Folkhälsanin Tutkimussäätiö, Göran Gustafssons Stiftelser, Stiftelsen för Strategisk Forskning, VINNOVA, Academy of Finland, Lunds Universitet, Hjärt-Lungfonden, Linköpings Universitet, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Novo Nordisk, Vetenskapsrådet, Helse Midt-Norge, Umeå Universitet, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Uppsala Universitet, Svenska Kulturfonden, Science for Life Laboratory, Landstinget Västmanland, Novo Nordisk Fonden, Skånes universitetssjukhus, Diabetestutkimussäätiö, Region Uppsala, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Uppsala Multidisciplinary Center for Advanced Computational Science, Faculty of Medicine and Health, University of Sydney, Norwegian Institute of Public Health
Awards: G1045075726, G1051078291, G1441096865, G1511761344, G1573152588, G159915776, G1621382071, G1754968858, SIMPLER, G1969828773, G2004031785, G2061701933, G2131505204, G2197756838, Center of Excellence in Complex Disease Genetics-from Discovery to Precision Medicine, Diabetes subclassification - new genes and novel mechanisms, Molecular profiling of the Central Swedish Cohorts & Biobank: Entering precision medicine for healthy ageing, G263730981, Machine learning - the way to successful events, G271718852, G2909646403, G3125548372, G3187080867, G3197512459, G3273365655, Diet, biomarker determinants and pharmacologic interventions to predict and prevent frailty fractures in women and men, G3582365513, Users as experts - reducing barriers on the web by utilising the target groups’ experiences, G3660823713, G3676281905, Personalized anti-fracture treatment, The role of gut microbiota in health and disease: population based studies with main focus on cardiometabolic diseases, G4007160920, Central Sweden Cohorts & Biobank, G4377315820, G4632909464, Molecular and microbial drivers of atherosclerosis, The microbiome in the gut-kidney-cardiovascular axis, G4928824683, G5367026566, G55242246, G5698529245, The microbiome in the gut-kidney-cardiovascular axis, G633570985, G6373074959, G6435640130, G6565658171, G6625919268, Cardiovascular autonomic dysfunction – a neglected risk factor for cardiovascular disease?, G6954103924, Gut microbiome diversity – does it matter? Antibiotics, genetics and a blood test to assess the impact on cardiometabolic disease, G7198575154, G7388034200, Towards precision medicine for heart failure and myocardial disease: myocardial genomics, single cell transcriptomics, and plasma profiling, G7569742080, G7615508626, LUDC-IRC för individanpassad medicin i diabetes, Fail-safe medical technology tube connector for infusion, transfusion and dialysis., Novel molecular mechanisms underlying diabetic complications, G7855199912, G796431723, G804694337, G8436673617, G8482826862, Center of Excellence in Complex Disease Genetics-from Discovery to Precision Medicine, G8764181438, NAISS, Process optimization of glassworks with AI
OpenAlex ID: W7128801880