The HUNT study identifies host genetic factors reproducibly associated with human gut microbiota composition
The gut microbiota is associated with human health and disease. Here we conducted a genome-wide association study of host genetic factors influencing gut microbiota composition in 12,652 individuals from the Trøndelag Health Study (HUNT), with replication in Nordic cohorts (n = 16,017-21,976). We identified 12 reproducible SNP-species associations across six genomic loci, including known (LCT, ABO) and novel (HLA-DQB1, MUC12, SLC37A2, FUT2) regions. Additionally, we detected genetic signals associated with gut microbiota functional modules at three loci (LCT, ABO, FUT2). Follow-up analyses suggest that these host-microbiota associations are linked to the pathogenesis of celiac disease and hemorrhoidal disease. Mendelian randomization analyses provided evidence supporting a causal effect of body mass index on gut microbiota composition. These findings highlight the interplay between host genetics and gut microbiota for human health and disease.
Authors
- Gabriel Baldanzi (ORCID: https://orcid.org/0000-0003-3962-3953)
- Louise Grahnemo (ORCID: https://orcid.org/0000-0001-5276-6612)
- Aron C. Eklund (ORCID: https://orcid.org/0000-0003-0861-1001)
- Claes Ohlsson
- T Fall
- Rebecka Hjort (ORCID: https://orcid.org/0000-0002-8057-3882)
- Per Lundmark
- Thaher Pelaseyed (ORCID: https://orcid.org/0000-0002-6434-3913)
- Robin Mjelle (ORCID: https://orcid.org/0000-0003-3509-4134)
- Anna E. Törnqvist (ORCID: https://orcid.org/0000-0003-2621-9038)
- Arnulf Langhammer (ORCID: https://orcid.org/0000-0001-5296-6673)
- Koen F. Dekkers (ORCID: https://orcid.org/0000-0002-4074-7235)
- Johan Svensson (ORCID: https://orcid.org/0000-0002-0427-5699)
- Karl Michaëlsson (ORCID: https://orcid.org/0000-0003-2815-1217)
- Kamalita Pertiwi (ORCID: https://orcid.org/0000-0003-2861-9051)
- Marta R. Moksnes (ORCID: https://orcid.org/0000-0002-2690-5153)
- Janne Marie Moll (ORCID: https://orcid.org/0000-0002-3514-4528)
- Eivind Coward
- Henrik Bjørn Nielsen
- Gunnar Engström
- Eivind Ness-Jensen
- B M Brumpton
- K Hveem
- Lei Li
- Maria Nethander
- Guro F. Giskeødegård
Institutions
- Uppsala University (SE)
- Karolinska University Hospital (SE)
- Lund University (SE)
- Norwegian University of Science and Technology (NO)
- Levanger Hospital (NO)
- Sahlgrenska University Hospital (SE)
- Karolinska Institutet (SE)
- Clinical Microbiomics (Denmark) (DK)
- Region Västra Götaland (SE)
- St Olav's University Hospital (NO)
- Skaraborg Hospital (SE)
- University of Gothenburg (SE)
Publication Details
- Journal
- Nature Genetics
- Published
- 2026-02-13
- DOI
- https://doi.org/10.1038/s41588-026-02502-4
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Norges Teknisk-Naturvitenskapelige Universitet
- School of Public Health, University of Michigan
- European Commission
- VINNOVA
- Lunds Universitet
- Svenska Sällskapet för Medicinsk Forskning
- Hjärt-Lungfonden
- Linköpings Universitet
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Novo Nordisk
- Stockholms Läns Landsting
- Vetenskapsrådet
- Helse Midt-Norge
- Umeå Universitet
- Norges Forskningsråd
- Sahlgrenska Universitetssjukhuset
- Göteborgs Universitet
- Uppsala Universitet
- Novo Nordisk Fonden
- Skånes universitetssjukhus
- National Institutes of Health
- Medical School, University of Michigan
- Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet
- Uppsala Multidisciplinary Center for Advanced Computational Science
- Faculty of Medicine and Health, University of Sydney
- Norwegian Institute of Public Health
- National Institute of Diabetes and Digestive and Kidney Diseases