# The HUNT study identifies host genetic factors reproducibly associated with human gut microbiota composition

## TL;DR

This study finds genetic factors in humans that are linked to gut microbiota composition and suggests a causal link between body mass index and gut microbiome features.

## Contribution

Identifies 12 reproducible SNP–species associations and provides causal evidence for BMI's effect on gut microbiota.

## Key findings

- 12 reproducible SNP–species associations were identified across six genomic loci.
- Mendelian randomization showed a causal effect of body mass index on gut microbiota composition.
- Host–microbiota associations were linked to celiac and hemorrhoidal disease pathogenesis.

## Abstract

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.

Genome-wide analyses in the Norwegian HUNT study with replication in Swedish and Finnish cohorts identify host genetic variants associated with gut microbiome features and provide evidence of a causal effect of body mass index on gut microbiota composition.