title: A pooling-based genomewide association study identifies genetic variants associated with Staphylococcus aureus colonization in chronic rhinosinusitis patients.
abstract: BACKGROUND
  Staphylococcus aureus (S. aureus) has been implicated in the pathogenesis of chronic rhinosinusitis (CRS). However, host factors contributing to susceptibility to S. aureus colonization in CRS remain unknown. We wish to investigate, using a pooled genomewide association study (pGWAS), single-nucleotide polymorphisms (SNPs) associated with S. aureus carriage in CRS patients.
  
  
  METHODS
  An existing population of 408 CRS patients and 190 controls was prospectively recruited for genetic association studies. All CRS patients had an endoscopic swab culture as part of phenotyping. A pGWAS compared DNA pools from patients with and without S. aureus colonization using the Illumina HumanHap 1M BeadChip, which interrogates 1 million SNPs. Top-ranked SNPs associated with S. aureus colonization were selected according to biallelic differences and silhouette rank, and confirmed by individual genotyping using the Sequenom platform. PLINK software was used for genetic association tests. Ingenuity pathway analysis was used to identify canonical and signaling pathways enriched for genes neighboring associated SNPs, as well as identification of the underlying biological mechanisms.
  
  
  RESULTS
  Thirty-nine top priority SNPs were selected for individual genotyping. Out of 39 SNPs, 23 were associated (p < 0.05) with S. aureus colonization in CRS patients. These SNPs are located within or near 21 genes reported to be implicated in several diseases, endocytic internalization, and bacterial recognition.
  
  
  CONCLUSIONS
  These results suggest novel host genetic factors influencing susceptibility to S. aureus colonization in CRS. Identifying implicated mechanisms may offer new insights into pathogenesis of CRS.
authors.affiliation: Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
authors.forename: Chantale
authors.initials: C
authors.lastname: Cormier
authors.forename: Léandra
authors.initials: L
authors.lastname: Mfuna Endam
authors.forename: Abdelali
authors.initials: A
authors.lastname: Filali-Mouhim
authors.forename: Pierre
authors.initials: P
authors.lastname: Boisvert
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Boulay
authors.forename: Sophie
authors.initials: S
authors.lastname: Vallée-Smedja
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.forename: Martin
authors.initials: M
authors.lastname: Desrosiers
mesh_terms: D000328:Adult; D002170:Canada; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics; D006801:Humans; D053564:Keratins, Hair-Specific / Q000235:genetics; D053531:Keratins, Type II / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012220:Rhinitis / Q000150:complications / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D012852:Sinusitis / Q000150:complications / Q000235:genetics*; D013203:Staphylococcal Infections / Q000150:complications / Q000235:genetics*; D013211:Staphylococcus aureus / Q000276:immunology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics
chemical_list: C494987:GFRA1 protein, human; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C473406:KRT74 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II; D020830:rac1 GTP-Binding Protein
keywords: Staphylococcus aureus; chronic rhinosinusitis; genomewide association study; inflammation; single-nucleotide polymorphism