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

Gao，Jingyuan1; Yang，Yuqiong2; Xiang，Xiaopeng3; Zheng，Huimin4; Yi，Xinzhu1; Wang，Fengyan2; Liang，Zhenyu2; Chen，Dandan5; Shi，Weijuan2; Wang，Lingwei5; Wu，Di5; Feng，Shengchuan2; Huang，Qiaoyun2; Li，Xueping2; Shu，Wensheng1; Chen，Rongchang2,5; Zhong，Nanshan2; Wang，Zhang6

2024-12-01

10.1186/s12931-024-02805-2

Respiratory Research   影响因子和分区

1465-9921

1465-993X

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.

Airway microbiome COPD GWAS Mendelian randomization Microbiome-host genetic interaction

SCI

英语

其他

CLINICAL MEDICINE

2-s2.0-85190428394

Scopus

1.Institute of Ecological Sciences,School of Life Sciences,South China Normal University,Guangzhou,Guangdong Province,China
2.State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,National Center for Respiratory Medicine,Guangzhou Institute of Respiratory Health,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China
3.The Hong Kong Polytechnic University,Hung Hom Kowloon,Hong Kong
4.Department of Obstetrics and Gynecology,The First People’s Hospital of Foshan,Foshan,Guangdong Province,China
5.Department of Pulmonary and Critical Care Medicine,Shenzhen Institute of Respiratory Diseases,Shenzhen People’s Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,Guangdong Province,China
6.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

Gao，Jingyuan,Yang，Yuqiong,Xiang，Xiaopeng,et al. Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease[J]. Respiratory Research,2024,25(1).

Gao，Jingyuan.,Yang，Yuqiong.,Xiang，Xiaopeng.,Zheng，Huimin.,Yi，Xinzhu.,...&Wang，Zhang.(2024).Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease.Respiratory Research,25(1).

Gao，Jingyuan,et al."Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease".Respiratory Research 25.1(2024).