Human and bacterial genetic variation shape oral microbiomes and health

Summary ParagraphHuman genetic variation influences all aspects of our biology, including the oral cavity1-3, through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a persons oral microbiome and potentially promote its dysbiosis3-5. We characterized the oral microbiomes of 12,519 people by re-analyzing whole-genome sequencing reads from previously sequenced saliva-derived DNA. Human genetic variation at 11 loci (10 novel) associated with variation in oral microbiome composition. Several of these related to carbohydrate availability; the strongest association (p=3.0x10-188) involved the common FUT2 W154X loss-of-function variant, which associated with the abundances of 58 bacterial species. Human host genetics also appeared to powerfully shape genetic variation within oral bacterial species: these 11 host genetic variants also associated with variation of gene dosages in 68 regions of bacterial genomes. Common, multi-allelic copy-number variation of AMY1, which encodes salivary amylase, associated with oral microbiome composition (p=1.5x10-53) and with dentures use in UK Biobank (p=5.9x10-35, n=418,039) but not with body mass index (p=0.85), suggesting that amylase abundance impacts health by influencing the oral microbiome. Two other microbiome composition-associated loci, FUT2 and PITX1, also significantly associated with dentures risk, collectively nominating numerous host-microbial interactions that contribute to tooth decay.