{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin B"],"funding":["Natural Sciences and Engineering Research Council of Canada","Canada Research Chairs Program","Government of Ontario","Cystic Fibrosis Foundation","Cystic Fibrosis Canada","Genome Canada","Canadian Institutes of Health Research"],"pagination":["2400062"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11540985"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["64(5)"],"pubmed_abstract":["<h4>Background</h4><i>Pseudomonas aeruginosa</i> is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing <i>CFTR</i> (CF transmembrane conductance regulator) variations contribute ∼85% of the variation in chronic <i>P. aeruginosa</i> infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to <i>P. aeruginosa</i> infection.<h4>Materials and methods</h4>We conducted a genome-wide association study of chronic <i>P. aeruginosa</i> infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic <i>P. aeruginosa</i> infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis.<h4>Results</h4>Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98×10<sup>-8</sup>) and rs927553 (chr13q12.12; p=1.91×10<sup>-8</sup>) were associated with chronic <i>P. aeruginosa</i> infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic <i>P. aeruginosa</i> infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic <i>P. aeruginosa</i> infection age (β=0.782 years, p=4.24×10<sup>-4</sup>). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012).<h4>Conclusions</h4>We identified two novel loci that are associated with chronic <i>P. aeruginosa</i> infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between <i>P. aeruginosa</i> infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF."],"journal":["The European respiratory journal"],"pubmed_title":["Genome-wide association study of susceptibility to <i>Pseudomonas aeruginosa</i> infection in cystic fibrosis."],"pmcid":["PMC11540985"],"funding_grant_id":["FRN-167282","STRUG17PO","OGI-148","FRN-310732","RGPIN-04934","RGPIN-2015-03742","2626"],"pubmed_authors":["Mohand Oumoussa B","Strug LJ","Guillot L","Corvol H","Mesinele J","Waters V","Calmel C","Sun L","Lin B","Lin YC","Boelle PY","Lin F","Keenan K","Gong J"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide association study of susceptibility to <i>Pseudomonas aeruginosa</i> infection in cystic fibrosis.","description":"<h4>Background</h4><i>Pseudomonas aeruginosa</i> is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing <i>CFTR</i> (CF transmembrane conductance regulator) variations contribute ∼85% of the variation in chronic <i>P. aeruginosa</i> infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to <i>P. aeruginosa</i> infection.<h4>Materials and methods</h4>We conducted a genome-wide association study of chronic <i>P. aeruginosa</i> infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic <i>P. aeruginosa</i> infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis.<h4>Results</h4>Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98×10<sup>-8</sup>) and rs927553 (chr13q12.12; p=1.91×10<sup>-8</sup>) were associated with chronic <i>P. aeruginosa</i> infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic <i>P. aeruginosa</i> infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic <i>P. aeruginosa</i> infection age (β=0.782 years, p=4.24×10<sup>-4</sup>). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012).<h4>Conclusions</h4>We identified two novel loci that are associated with chronic <i>P. aeruginosa</i> infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between <i>P. aeruginosa</i> infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-08T06:28:23.485Z","creation":"2026-06-08T03:14:26.891Z"},"accession":"S-EPMC11540985","cross_references":{"pubmed":["39117430"],"doi":["10.1183/13993003.00062-2024"]}}