Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease

Respir Res. 2024 Apr 16;25(1):165. doi: 10.1186/s12931-024-02805-2.ABSTRACTLittle is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10-5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10-8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causa...

Source: Respiratory Care - April 15, 2024 Category: Respiratory Medicine Authors: Jingyuan Gao Yuqiong Yang Xiaopeng Xiang Huimin Zheng Xinzhu Yi Fengyan Wang Zhenyu Liang Dandan Chen Weijuan Shi Lingwei Wang Di Wu Shengchuan Feng Qiaoyun Huang Xueping Li Wensheng Shu Rongchang Chen Nanshan Zhong Zhang Wang Source Type: research