A genome-wide association study reveals human genetic impact on the nasal microbial diversity, taxa and functions

Abstract

The nasal cavity harbors diverse microbiota that contribute to human health and respiratory diseases. However, whether and to what extent the host genome shapes the nasal microbiome remains largely unknown. Here, by dissecting the human genome and nasal metagenome data from 1,401 healthy individuals, we demonstrated that host genetic principal components strongly correlated with the nasal microbiota diversity and composition. The genetic association analyses identified 63 genome-wide significant loci affecting the nasal microbial taxa and functions, of which 2 loci reached study-wide significance (p < 1.7 × 10− 10): rs73268759 within CAMK2A associated with genus Actinomyces and family Actinomycetaceae; and rs35211877 near POM121L12 with Gemella asaccharolytica. In addition to respiratory-related diseases, the associated loci are mainly implicated in cardiometabolic or neuropsychiatric diseases. Functional analysis showed the associated genes were most significantly expressed in the nasal airway epithelium tissue and enriched in the calcium signaling and hippo signaling pathway. Further observational and Mendelian randomization analyses consistently revealed that several metabolites such as cystine, cystathionine, and glutamic acid play crucial roles in the host metabolism-nasal microbiota interplays. This study indicates that the contribution of the host genome to the nasal microbiome is not weaker than that of other host factors.