A pooling-based genomewide association study identifies genetic variants associated with Staphylococcus aureus colonization in chronic rhinosinusitis patients

作者：Cormier Chantale; Endam Leandra Mfuna; Filali Mouhim Abdelali; Boisvert Pierre; Boulet Louis Philippe; Boulay Marie Eve; Vallee Smedja Sophie; Bosse Yohan; Desrosiers Martin^*

来源：International Forum of Allergy & Rhinology, 2014, 4(3): 207-215.

DOI：10.1002/alr.21276

• Staphylococcus aureus
• single-nucleotide polymorphism
• inflammation
• genomewide association study
• chronic rhinosinusitis

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.
Conclusion
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.

• 出版日期2014-3
• 单位McGill