A polygenic risk score for rheumatoid arthritis (RA), which was developed using a cohort of identical twins who did not have RA and validated against a diagnosis of RA using samples from the UK Biobank, was associated with the presence of Prevotella spp. in the gut in the absence of RA, suggesting an association between gut microbiota and host genotype before disease onset. The association between genes and microbiota was further validated in a cohort of first-degree relatives of patients with RA, in whom Prevotella spp. were associated with the HLA-DRB1 shared epitope and with preclinical arthritis.