{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:34:50Z","timestamp":1793658890657,"version":"4.5.1"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>OR51E1\u2013OR51E2<\/jats:italic>\n                    locus, encoding sensors for microbiome-derived fatty acids, associated with microbial richness. We further identified 15 study-wide significant genetic associations (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20095.4\u2009\u00d7\u200910\n                    <jats:sup>\u221211<\/jats:sup>\n                    ) involving eight loci and 14 common bacterial species, of which 11 associations at six loci were replicated. The results confirm previously reported associations at\n                    <jats:italic>LCT<\/jats:italic>\n                    ,\n                    <jats:italic>ABO<\/jats:italic>\n                    and\n                    <jats:italic>FUT2<\/jats:italic>\n                    , and provide evidence for new loci\n                    <jats:italic>MUC12<\/jats:italic>\n                    ,\n                    <jats:italic>CORO7\u2013HMOX2<\/jats:italic>\n                    ,\n                    <jats:italic>SLC5A11<\/jats:italic>\n                    ,\n                    <jats:italic>FOXP1<\/jats:italic>\n                    and\n                    <jats:italic>FUT3\u2013FUT6<\/jats:italic>\n                    , 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.\n                  <\/jats:p>","DOI":"10.1038\/s41588-026-02512-2","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:02:56Z","timestamp":1770976976000},"page":"540-549","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genome-wide association analyses highlight the role of the intestinal molecular environment in human gut microbiota variation"],"prefix":"10.1038","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-7235","authenticated-orcid":false,"given":"Koen F.","family":"Dekkers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-9051","authenticated-orcid":false,"given":"Kamalita","family":"Pertiwi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-3953","authenticated-orcid":false,"given":"Gabriel","family":"Baldanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2334-8802","authenticated-orcid":false,"given":"Per","family":"Lundmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Hammar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-5153","authenticated-orcid":false,"given":"Marta Riise","family":"Moksnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1323-3555","authenticated-orcid":false,"given":"Eivind","family":"Coward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-906X","authenticated-orcid":false,"given":"Maria","family":"Nethander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5938-8222","authenticated-orcid":false,"given":"Ghassan Ali","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Miari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-5772","authenticated-orcid":false,"given":"Diem","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Sayols-Baixeras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0861-1001","authenticated-orcid":false,"given":"Aron C.","family":"Eklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1756-0875","authenticated-orcid":false,"given":"Jacob Bak","family":"Holm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2281-5713","authenticated-orcid":false,"given":"H. Bj\u00f8rn","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Gazolla","family":"Volpiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-9958","authenticated-orcid":false,"given":"Guillaume","family":"M\u00e9ric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7164-6525","authenticated-orcid":false,"given":"Manonanthini","family":"Thangam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liisa","family":"Hakaste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiinamaija","family":"Tuomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6513-2384","authenticated-orcid":false,"given":"Emma","family":"Ahlqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-6377","authenticated-orcid":false,"given":"Frank","family":"Reimann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4232-2898","authenticated-orcid":false,"given":"Fiona M.","family":"Gribble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9633-2805","authenticated-orcid":false,"given":"Claes","family":"Ohlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Hveem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"Melander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-8459","authenticated-orcid":false,"given":"Peter M.","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Engstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Gustav","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Micha\u00eblsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"\u00c4rnl\u00f6v","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-2503","authenticated-orcid":false,"given":"Marju","family":"Orho-Melander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-5866","authenticated-orcid":false,"given":"Tove","family":"Fall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"2512_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","volume":"19","author":"Y Fan","year":"2021","unstructured":"Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19, 55\u201371 (2021).","journal-title":"Nat. Rev. Microbiol."},{"key":"2512_CR2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","volume":"19","author":"LH Morais","year":"2021","unstructured":"Morais, L. H., Schreiber, H. L. & Mazmanian, S. K. The gut microbiota-brain axis in behaviour and brain disorders. Nat. Rev. Microbiol. 19, 241\u2013255 (2021).","journal-title":"Nat. Rev. Microbiol."},{"key":"2512_CR3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1126\/science.aba5483","volume":"373","author":"L Grieneisen","year":"2021","unstructured":"Grieneisen, L. et al. Gut microbiome heritability is nearly universal but environmentally contingent. Science 373, 181\u2013186 (2021).","journal-title":"Science"},{"key":"2512_CR4","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.chom.2016.04.017","volume":"19","author":"JK Goodrich","year":"2016","unstructured":"Goodrich, J. K. et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19, 731\u2013743 (2016).","journal-title":"Cell Host Microbe"},{"key":"2512_CR5","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41588-020-00763-1","volume":"53","author":"A Kurilshikov","year":"2021","unstructured":"Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156\u2013165 (2021).","journal-title":"Nat. Genet."},{"key":"2512_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1086-x","volume":"17","author":"J Debelius","year":"2016","unstructured":"Debelius, J. et al. Tiny microbes, enormous impacts: what matters in gut microbiome studies? Genome Biol. 17, 217 (2016).","journal-title":"Genome Biol."},{"key":"2512_CR7","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41588-021-00992-y","volume":"54","author":"EA Lopera-Maya","year":"2022","unstructured":"Lopera-Maya, E. A. et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat. Genet. 54, 143\u2013151 (2022).","journal-title":"Nat. Genet."},{"key":"2512_CR8","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/ng.3693","volume":"48","author":"W Turpin","year":"2016","unstructured":"Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413\u20131417 (2016).","journal-title":"Nat. Genet."},{"key":"2512_CR9","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/s41588-021-00991-z","volume":"54","author":"Y Qin","year":"2022","unstructured":"Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet. 54, 134\u2013142 (2022).","journal-title":"Nat. Genet."},{"key":"2512_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0759-1","volume":"16","author":"R Blekhman","year":"2015","unstructured":"Blekhman, R. et al. Host genetic variation impacts microbiome composition across human body sites. Genome Biol. 16, 191 (2015).","journal-title":"Genome Biol."},{"key":"2512_CR11","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41588-021-00983-z","volume":"54","author":"S Sanna","year":"2022","unstructured":"Sanna, S., Kurilshikov, A., van der Graaf, A., Fu, J. & Zhernakova, A. Challenges and future directions for studying effects of host genetics on the gut microbiome. Nat. Genet. 54, 100\u2013106 (2022).","journal-title":"Nat. Genet."},{"key":"2512_CR12","doi-asserted-by":"publisher","first-page":"1425489","DOI":"10.3389\/fmicb.2024.1425489","volume":"15","author":"S Pita","year":"2024","unstructured":"Pita, S. et al. CHAMP delivers accurate taxonomic profiles of the prokaryotes, eukaryotes, and bacteriophages in the human microbiome. Front. Microbiol. 15, 1425489 (2024).","journal-title":"Front. Microbiol."},{"key":"2512_CR13","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nature12506","volume":"500","author":"E Le Chatelier","year":"2013","unstructured":"Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541\u2013546 (2013).","journal-title":"Nature"},{"key":"2512_CR14","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","volume":"66","author":"V Pascal","year":"2017","unstructured":"Pascal, V. et al. A microbial signature for Crohn\u2019s disease. Gut 66, 813\u2013822 (2017).","journal-title":"Gut"},{"key":"2512_CR15","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","volume":"369","author":"GTEx Consortium","year":"2020","unstructured":"GTEx Consortium The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318\u20131330 (2020).","journal-title":"Science"},{"key":"2512_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-29692-x","volume":"16","author":"T Hegelmaier","year":"2023","unstructured":"Hegelmaier, T. et al. Supplementation with short-chain fatty acids and the prebiotic 2FL improves clinical outcome in Parkinson\u2019s disease: a randomized double-blind prospective study. Sci. Rep. 16, 315 (2023).","journal-title":"Sci. Rep."},{"key":"2512_CR17","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1002\/jcp.25929","volume":"233","author":"Z Chen","year":"2018","unstructured":"Chen, Z., Zhao, H., Fu, N. & Chen, L. The diversified function and potential therapy of ectopic olfactory receptors in non-olfactory tissues. J. Cell. Physiol. 233, 2104\u20132115 (2018).","journal-title":"J. Cell. Physiol."},{"key":"2512_CR18","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.3390\/molecules26051416","volume":"26","author":"J Meijerink","year":"2021","unstructured":"Meijerink, J. The intestinal fatty acid-enteroendocrine interplay, emerging roles for olfactory signaling and serotonin conjugates. Molecules 26, 1416 (2021).","journal-title":"Molecules"},{"key":"2512_CR19","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/s42255-024-01044-5","volume":"6","author":"S Tan","year":"2024","unstructured":"Tan, S. et al. Interaction between the gut microbiota and colonic enteroendocrine cells regulates host metabolism. Nat. Metab. 6, 1076\u20131091 (2024).","journal-title":"Nat. Metab."},{"key":"2512_CR20","doi-asserted-by":"publisher","first-page":"C502","DOI":"10.1152\/ajpcell.00454.2019","volume":"318","author":"K Kotlo","year":"2020","unstructured":"Kotlo, K. et al. The olfactory G protein-coupled receptor (Olfr-78\/OR51E2) modulates the intestinal response to colitis. Am. J. Physiol. Cell Physiol. 318, C502\u2013C513 (2020).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2512_CR21","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1210\/en.2018-00261","volume":"159","author":"VB Lu","year":"2018","unstructured":"Lu, V. B., Gribble, F. M. & Reimann, F. Free fatty acid receptors in enteroendocrine cells. Endocrinology 159, 2826\u20132835 (2018).","journal-title":"Endocrinology"},{"key":"2512_CR22","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41586-023-05915-x","volume":"619","author":"JW Hickey","year":"2023","unstructured":"Hickey, J. W. et al. Organization of the human intestine at single-cell resolution. Nature 619, 572\u2013584 (2023).","journal-title":"Nature"},{"key":"2512_CR23","doi-asserted-by":"publisher","first-page":"7751","DOI":"10.1113\/JP287463","volume":"603","author":"CA Smith","year":"2025","unstructured":"Smith, C. A. et al. Single-cell transcriptomics of human organoid-derived enteroendocrine cell populations from the small intestine. J. Physiol. 603, 7751\u20137763 (2025).","journal-title":"J. Physiol."},{"key":"2512_CR24","doi-asserted-by":"publisher","first-page":"e0308942","DOI":"10.1371\/journal.pone.0308942","volume":"19","author":"CA Smith","year":"2024","unstructured":"Smith, C. A. et al. Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract. PLoS ONE 19, e0308942 (2024).","journal-title":"PLoS ONE"},{"key":"2512_CR25","doi-asserted-by":"publisher","first-page":"100069","DOI":"10.1016\/j.xgen.2021.100069","volume":"1","author":"F Bonfiglio","year":"2021","unstructured":"Bonfiglio, F. et al. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome. Cell Genom. 1, 100069 (2021).","journal-title":"Cell Genom."},{"key":"2512_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8, 1826 (2017).","journal-title":"Nat. Commun."},{"key":"2512_CR27","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1002\/ijc.27836","volume":"132","author":"RC Travis","year":"2013","unstructured":"Travis, R. C. et al. Genetic variation in the lactase gene, dairy product intake and risk for prostate cancer in the European prospective investigation into cancer and nutrition. Int. J. Cancer 132, 1901\u20131910 (2013).","journal-title":"Int. J. Cancer"},{"key":"2512_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02287-x","volume":"7","author":"M Li","year":"2017","unstructured":"Li, M. et al. Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism. Sci. Rep. 7, 2812 (2017).","journal-title":"Sci. Rep."},{"key":"2512_CR29","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1111\/mmi.14681","volume":"115","author":"JM Garber","year":"2021","unstructured":"Garber, J. M., Hennet, T. & Szymanski, C. M. Significance of fucose in intestinal health and disease. Mol. Microbiol. 115, 1086\u20131093 (2021).","journal-title":"Mol. Microbiol."},{"key":"2512_CR30","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41588-020-00747-1","volume":"53","author":"MC R\u00fchlemann","year":"2021","unstructured":"R\u00fchlemann, M. C. et al. Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome. Nat. Genet. 53, 147\u2013155 (2021).","journal-title":"Nat. Genet."},{"key":"2512_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-11819-z","volume":"12","author":"JS Glover","year":"2022","unstructured":"Glover, J. S., Ticer, T. D. & Engevik, M. A. Characterizing the mucin-degrading capacity of the human gut microbiota. Sci. Rep. 12, 8456 (2022).","journal-title":"Sci. Rep."},{"key":"2512_CR32","doi-asserted-by":"publisher","first-page":"7932","DOI":"10.1074\/jbc.272.12.7932","volume":"272","author":"LC Hoskins","year":"1997","unstructured":"Hoskins, L. C., Boulding, E. T. & Larson, G. Purification and characterization of blood group A-degrading isoforms of alpha-N-acetylgalactosaminidase from Ruminococcus torques strain IX-70. J. Biol. Chem. 272, 7932\u20137939 (1997).","journal-title":"J. Biol. Chem."},{"key":"2512_CR33","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.279.5349.373","volume":"279","author":"D Ilver","year":"1998","unstructured":"Ilver, D. et al. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279, 373\u2013377 (1998).","journal-title":"Science"},{"key":"2512_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07460-y","volume":"9","author":"E Ferkingstad","year":"2018","unstructured":"Ferkingstad, E. et al. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. Nat. Commun. 9, 5101 (2018).","journal-title":"Nat. Commun."},{"key":"2512_CR35","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41586-021-04064-3","volume":"600","author":"SE Graham","year":"2021","unstructured":"Graham, S. E. et al. The power of genetic diversity in genome-wide association studies of lipids. Nature 600, 675\u2013679 (2021).","journal-title":"Nature"},{"key":"2512_CR36","doi-asserted-by":"publisher","first-page":"e0275671","DOI":"10.1371\/journal.pone.0275671","volume":"17","author":"T Lang","year":"2022","unstructured":"Lang, T. & Pelaseyed, T. Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. PLoS ONE 17, e0275671 (2022).","journal-title":"PLoS ONE"},{"key":"2512_CR37","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1042\/EBC20220121","volume":"67","author":"G Raba","year":"2023","unstructured":"Raba, G. & Luis, A. S. Mucin utilization by gut microbiota: recent advances on characterization of key enzymes. Essays Biochem. 67, 345\u2013353 (2023).","journal-title":"Essays Biochem."},{"key":"2512_CR38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1348-0421.2000.tb01242.x","volume":"44","author":"A Kageyama","year":"2000","unstructured":"Kageyama, A. & Benno, Y. Coprobacillus catenaformis gen. nov., sp. nov., a new genus and species isolated from human feces. Microbiol. Immunol. 44, 23\u201328 (2000).","journal-title":"Microbiol. Immunol."},{"key":"2512_CR39","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1053\/j.gastro.2022.06.020","volume":"163","author":"M El-Salhy","year":"2022","unstructured":"El-Salhy, M. et al. Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at 3 years after transplantation. Gastroenterology 163, 982\u2013994.e14 (2022).","journal-title":"Gastroenterology"},{"key":"2512_CR40","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1016\/j.chom.2022.08.013","volume":"30","author":"U Boulund","year":"2022","unstructured":"Boulund, U. et al. Gut microbiome associations with host genotype vary across ethnicities and potentially influence cardiometabolic traits. Cell Host Microbe 30, 1464\u20131480.e6 (2022).","journal-title":"Cell Host Microbe"},{"key":"2512_CR41","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1038\/ng.3663","volume":"48","author":"MJ Bonder","year":"2016","unstructured":"Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407\u20131412 (2016).","journal-title":"Nat. Genet."},{"key":"2512_CR42","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/ni.2034","volume":"12","author":"X Feng","year":"2011","unstructured":"Feng, X. et al. Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells. Nat. Immunol. 12, 544\u2013550 (2011).","journal-title":"Nat. Immunol."},{"key":"2512_CR43","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1161\/CIRCRESAHA.118.314402","volume":"125","author":"T Zhuang","year":"2019","unstructured":"Zhuang, T. et al. Endothelial Foxp1 suppresses atherosclerosis via modulation of Nlrp3 inflammasome activation. Circ. Res. 125, 590\u2013605 (2019).","journal-title":"Circ. Res."},{"key":"2512_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39403-7","volume":"14","author":"JB Lynch","year":"2023","unstructured":"Lynch, J. B. et al. Gut microbiota Turicibacter strains differentially modify bile acids and host lipids. Nat. Commun. 14, 3669 (2023).","journal-title":"Nat. Commun."},{"key":"2512_CR45","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1001\/jama.2018.19329","volume":"320","author":"LA Lotta","year":"2018","unstructured":"Lotta, L. A. et al. Association of genetic variants related to gluteofemoral vs abdominal fat distribution with type 2 diabetes, coronary disease, and cardiovascular risk factors. JAMA 320, 2553\u20132563 (2018).","journal-title":"JAMA"},{"key":"2512_CR46","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/s41564-020-0743-8","volume":"5","author":"DA Hughes","year":"2020","unstructured":"Hughes, D. A. et al. Genome-wide associations of human gut microbiome variation and implications for causal inference analyses. Nat. Microbiol. 5, 1079\u20131087 (2020).","journal-title":"Nat. Microbiol."},{"key":"2512_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04365-8","volume":"9","author":"Y Momozawa","year":"2018","unstructured":"Momozawa, Y. et al. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes. Nat. Commun. 9, 2427 (2018).","journal-title":"Nat. Commun."},{"key":"2512_CR48","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/ng.2982","volume":"46","author":"SY Shin","year":"2014","unstructured":"Shin, S. Y. et al. An atlas of genetic influences on human blood metabolites. Nat. Genet. 46, 543\u2013550 (2014).","journal-title":"Nat. Genet."},{"key":"2512_CR49","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.4014\/jmb.2205.05032","volume":"32","author":"DW Lee","year":"2022","unstructured":"Lee, D. W. et al. Agathobaculum butyriciproducens shows neuroprotective effects in a 6-OHDA-induced mouse model of Parkinson\u2019s disease. J. Microbiol. Biotechnol. 32, 1168\u20131177 (2022).","journal-title":"J. Microbiol. Biotechnol."},{"key":"2512_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/srep26923","volume":"6","author":"SY Lee","year":"2016","unstructured":"Lee, S. Y. et al. Arhgap17, a RhoGTPase activating protein, regulates mucosal and epithelial barrier function in the mouse colon. Sci. Rep. 6, 26923 (2016).","journal-title":"Sci. Rep."},{"key":"2512_CR51","doi-asserted-by":"publisher","first-page":"16088","DOI":"10.1038\/nmicrobiol.2016.88","volume":"1","author":"S Vieira-Silva","year":"2016","unstructured":"Vieira-Silva, S. et al. Species-function relationships shape ecological properties of the human gut microbiome. Nat. Microbiol. 1, 16088 (2016).","journal-title":"Nat. Microbiol."},{"key":"2512_CR52","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/s41564-018-0337-x","volume":"4","author":"M Valles-Colomer","year":"2019","unstructured":"Valles-Colomer, M. et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat. Microbiol. 4, 623\u2013632 (2019).","journal-title":"Nat. Microbiol."},{"key":"2512_CR53","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1126\/science.aad3503","volume":"352","author":"G Falony","year":"2016","unstructured":"Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560\u2013564 (2016).","journal-title":"Science"},{"key":"2512_CR54","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1126\/science.aad3369","volume":"352","author":"A Zhernakova","year":"2016","unstructured":"Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565\u2013569 (2016).","journal-title":"Science"},{"key":"2512_CR55","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/s41586-020-2881-9","volume":"587","author":"I Vujkovic-Cvijin","year":"2020","unstructured":"Vujkovic-Cvijin, I. et al. Host variables confound gut microbiota studies of human disease. Nature 587, 448\u2013454 (2020).","journal-title":"Nature"},{"key":"2512_CR56","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1111\/joim.12384","volume":"278","author":"G Bergstrom","year":"2015","unstructured":"Bergstrom, G. et al. The Swedish CArdioPulmonary BioImage Study: objectives and design. J. Intern. Med. 278, 645\u2013659 (2015).","journal-title":"J. Intern. Med."},{"key":"2512_CR57","doi-asserted-by":"publisher","DOI":"10.2196\/jmir.2458","volume":"15","author":"SE Christensen","year":"2013","unstructured":"Christensen, S. E. et al. Two new meal- and web-based interactive food frequency questionnaires: validation of energy and macronutrient intake. J. Med. Internet Res. 15, e109 (2013).","journal-title":"J. Med. Internet Res."},{"key":"2512_CR58","doi-asserted-by":"publisher","first-page":"16","DOI":"10.13172\/2053-079X-1-2-943","volume":"1","author":"H Harris","year":"2013","unstructured":"Harris, H. et al. The Swedish mammography cohort and the cohort of Swedish men: study design and characteristics of two population-based longitudinal cohorts. OA Epidemiol. 1, 16 (2013).","journal-title":"OA Epidemiol."},{"key":"2512_CR59","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10654-020-00695-4","volume":"36","author":"L Brunkwall","year":"2021","unstructured":"Brunkwall, L. et al. The Malmo Offspring Study (MOS): design, methods and first results. Eur. J. Epidemiol. 36, 103\u2013116 (2021).","journal-title":"Eur. J. Epidemiol."},{"key":"2512_CR60","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1093\/ije\/dys095","volume":"42","author":"S Krokstad","year":"2013","unstructured":"Krokstad, S. et al. Cohort profile: the HUNT study, Norway. Int. J. Epidemiol. 42, 968\u2013977 (2013).","journal-title":"Int. J. Epidemiol."},{"key":"2512_CR61","doi-asserted-by":"publisher","first-page":"e80","DOI":"10.1093\/ije\/dyac095","volume":"52","author":"BO \u00c5svold","year":"2023","unstructured":"\u00c5svold, B. O. et al. Cohort profile update: the HUNT study, Norway. Int. J. Epidemiol. 52, e80\u2013e91 (2023).","journal-title":"Int. J. Epidemiol."},{"key":"2512_CR62","doi-asserted-by":"publisher","first-page":"100193","DOI":"10.1016\/j.xgen.2022.100193","volume":"2","author":"BM Brumpton","year":"2022","unstructured":"Brumpton, B. M. et al. The HUNT study: a population-based cohort for genetic research. Cell Genom. 2, 100193 (2022).","journal-title":"Cell Genom."},{"key":"2512_CR63","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1161\/CIRCULATIONAHA.123.063914","volume":"148","author":"S Sayols-Baixeras","year":"2023","unstructured":"Sayols-Baixeras, S. et al. Streptococcus species abundance in the gut is linked to subclinical coronary atherosclerosis in 8973 participants from the SCAPIS cohort. Circulation 148, 459\u2013472 (2023).","journal-title":"Circulation"},{"key":"2512_CR64","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/S2213-8587(22)00113-9","volume":"10","author":"L Grahnemo","year":"2022","unstructured":"Grahnemo, L. et al. Cross-sectional associations between the gut microbe Ruminococcus gnavus and features of the metabolic syndrome. Lancet Diabetes Endocrinol. 10, 481\u2013483 (2022).","journal-title":"Lancet Diabetes Endocrinol."},{"key":"2512_CR65","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"2512_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1891-0","volume":"20","author":"DE Wood","year":"2019","unstructured":"Wood, D. E., Lu, J. & Langmead, B. Improved metagenomic analysis with Kraken 2. Genome Biol. 20, 257 (2019).","journal-title":"Genome Biol."},{"key":"2512_CR67","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/s41588-021-00870-7","volume":"53","author":"J Mbatchou","year":"2021","unstructured":"Mbatchou, J. et al. Computationally efficient whole-genome regression for quantitative and binary traits. Nat. Genet. 53, 1097\u20131103 (2021).","journal-title":"Nat. Genet."},{"key":"2512_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","journal-title":"Gigascience"},{"key":"2512_CR69","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12866-016-0708-5","volume":"16","author":"T Odamaki","year":"2016","unstructured":"Odamaki, T. et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 16, 90 (2016).","journal-title":"BMC Microbiol."},{"key":"2512_CR70","unstructured":"Mbatchou, J. Could regenie distinguish quantitative and binary covariates automatically? #61 GitHub https:\/\/github.com\/rgcgithub\/regenie\/issues\/61#issuecomment-735800868 (2020)."},{"key":"2512_CR71","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190\u20132191 (2010).","journal-title":"Bioinformatics"},{"key":"2512_CR72","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","volume":"53","author":"E Mountjoy","year":"2021","unstructured":"Mountjoy, E. et al. An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci. Nat. Genet. 53, 1527\u20131533 (2021).","journal-title":"Nat. Genet."},{"key":"2512_CR73","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41588-018-0279-5","volume":"51","author":"D Speed","year":"2019","unstructured":"Speed, D. & Balding, D. J. SumHer better estimates the SNP heritability of complex traits from summary statistics. Nat. Genet. 51, 277\u2013284 (2019).","journal-title":"Nat. Genet."},{"key":"2512_CR74","doi-asserted-by":"publisher","first-page":"113837","DOI":"10.1016\/j.psychres.2021.113837","volume":"299","author":"L Garvert","year":"2021","unstructured":"Garvert, L. et al. The association between genetically determined ABO blood types and major depressive disorder. Psychiatry Res. 299, 113837 (2021).","journal-title":"Psychiatry Res."},{"key":"2512_CR75","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1158\/1055-9965.EPI-23-0009","volume":"32","author":"J Kim","year":"2023","unstructured":"Kim, J. et al. Relationship between ABO blood group alleles and pancreatic cancer is modulated by secretor (FUT2) genotype, but not Lewis antigen (FUT3) genotype. Cancer Epidemiol. Biomarkers Prev. 32, 1242\u20131248 (2023).","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"2512_CR76","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul, A. et al. Robust relationship inference in genome-wide association studies. Bioinformatics 26, 2867\u20132873 (2010).","journal-title":"Bioinformatics"},{"key":"2512_CR77","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/ng2088","volume":"39","author":"J Marchini","year":"2007","unstructured":"Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906\u2013913 (2007).","journal-title":"Nat. Genet."},{"key":"2512_CR78","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1186\/1471-2105-11-288","volume":"11","author":"R Magi","year":"2010","unstructured":"Magi, R. & Morris, A. P. GWAMA: software for genome-wide association meta-analysis. BMC Bioinf. 11, 288 (2010).","journal-title":"BMC Bioinf."},{"key":"2512_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33050-0","volume":"13","author":"KF Dekkers","year":"2022","unstructured":"Dekkers, K. F. et al. An online atlas of human plasma metabolite signatures of gut microbiome composition. Nat. Commun. 13, 5370 (2022).","journal-title":"Nat. Commun."},{"key":"2512_CR80","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/s41588-018-0135-7","volume":"50","author":"J Zierer","year":"2018","unstructured":"Zierer, J. et al. The fecal metabolome as a functional readout of the gut microbiome. Nat. Genet. 50, 790\u2013795 (2018).","journal-title":"Nat. Genet."},{"key":"2512_CR81","doi-asserted-by":"publisher","first-page":"125743","DOI":"10.1016\/j.talanta.2024.125743","volume":"272","author":"R Fristedt","year":"2024","unstructured":"Fristedt, R., Ruppert, V., Trower, T., Cooney, J. & Landberg, R. Quantitation of circulating short-chain fatty acids in small volume blood samples from animals and humans. Talanta 272, 125743 (2024).","journal-title":"Talanta"},{"key":"2512_CR82","doi-asserted-by":"publisher","unstructured":"Lundmark, P. MolEpicUU\/GWAS_scripts: v1.0-NatGen. Zenodo https:\/\/doi.org\/10.5281\/zenodo.16947117 (2025).","DOI":"10.5281\/zenodo.16947117"},{"key":"2512_CR83","doi-asserted-by":"publisher","unstructured":"Dekkers, K. F. MolEpicUU\/GWAS_microbiome: v1. Zenodo https:\/\/doi.org\/10.5281\/zenodo.16925644 (2025).","DOI":"10.5281\/zenodo.16925644"}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02512-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02512-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02512-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:01:44Z","timestamp":1773424904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41588-026-02512-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":83,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["2512"],"URL":"https:\/\/doi.org\/10.1038\/s41588-026-02512-2","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]},"assertion":[{"value":"28 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. A.C.E., J.B.H. and H.B.N. are employees of Cmbio. J.\u00c4. has served on the advisory boards for Astella, AstraZeneca and Boehringer Ingelheim and has received lecturing fees from AstraZeneca, Boehringer Ingelheim and Novartis, all unrelated to the present work. P.M.N. has received lecture fees from Novartis, Novo Nordisk, Amgen and Boehringer Ingelheim. F.M.G. and F.R. received grant funding from Eli Lilly and AstraZeneca for other projects. C.O. is an applicant on filed patent applications on the effect of probiotics on bone metabolism. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}