Marta R. Moksnes, Eivind Coward, Maria Nethander, Koen F. Dekkers, Louise Grahnemo, Anna E. Törnqvist, Lei Li, Per Lundmark, Kamalita Pertiwi, Gabriel Baldanzi, Robin Mjelle, Janne Marie Moll, Aron C. Eklund, Henrik Bjørn Nielsen, Johan Svensson, Arnulf Langhammer, Guro F. Giskeødegård, B M Brumpton, Rebecka Hjort, Eivind Ness-Jensen, Gunnar Engström, Thaher Pelaseyed, Karl Michaëlsson, Marju Orho-Melander, T Fall, K Hveem, Claes Ohlsson
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.