The HUNT study identifies host genetic factors reproducibly associated with human gut microbiota composition.
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Moksnes MR, Coward E, Nethander M, Dekkers K, Grahnemo L, Törnqvist AE, Li L, Lundmark P, Pertiwi K, Baldanzi G, Mjelle R, Moll JM, Eklund AC, Nielsen HB, Svensson J, Langhammer A, Giskeødegård GF, Brumpton B, Hjort R, Ness-Jensen E, Engström G, Pelaseyed T, Michaëlsson K, Orho-Melander M, Fall T, Hveem K, Ohlsson C
Nat. Genet. 58 (3) 530-539 [2026-03-00; online 2026-02-13]
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.
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 41688637
DOI 10.1038/s41588-026-02502-4
Crossref 10.1038/s41588-026-02502-4
pmc: PMC12987729
pii: 10.1038/s41588-026-02502-4