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

Respir Res

Institute of Ecological Sciences, Biomedical Research Center, School of Life Sciences, State Key Laboratory of Respiratory Disease, South China Normal University, Guangzhou, Guangdong Province, China.

Published: April 2024

AI Article Synopsis

  • The study explores the relationship between human genetics and the airway microbiome using deep sequencing techniques in individuals with chronic obstructive pulmonary disease (COPD) and healthy controls.
  • It identifies over 5 million single nucleotide polymorphisms (SNPs) and finds significant associations between host genetic variation and the microbiome, accounting for about 12.11% of its variability.
  • The research suggests that host genetics plays a crucial role in influencing the airway microbiome, particularly in COPD, and proposes new hypotheses for understanding genetic-microbiome interactions in this disease context.

Article Abstract

Little 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), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10). 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 causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367891PMC
http://dx.doi.org/10.1186/s12931-024-02805-2DOI Listing

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