We reports a large-scale genome-wide association study (GWAS) of the tongue dorsum microbiome involving 13,397 Chinese participants from the CHARLS-4DSZ dataset. It identifies ten genome-wide significant and replicated loci linked to 17 microbial taxa, 8 pathways, and 1,783 gene families. The most prominent signal is the FUT2 I140F missense variant, which affects multiple taxa (notably Haemophilus sputorum, with P = 9.71e-51) independent of ABO blood groups, and is involved in fucose-mediated regulation of microbial metabolism. Most identified loci are functionally interpretable, correlating with tissue/single-cell gene expressions and host immunometabolic traits (e.g., POLI links to Haemophilus parahaemolyticus, white blood cell counts and triglyceride levels; SLC2A9 relates to serum uric acid and uric acid-degrading bacteria). Additionally, 239 significant associations between 94 microbial features and 43 host phenotypes are detected, and Mendelian randomization confirms 11 causal relationships between microbes and host metabolic indicators (e.g., gamma-glutamyl transferase, creatine, uric acid). Overall, the study provides a comprehensive genetic map of the oral microbiome, advancing the understanding of host-microbe interaction mechanisms.
刘小敏(Xiaomin Liu) (Thu,) studied this question.