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

Authors

  • Chantale Cormier MD,

    1. Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada
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  • Léandra Mfuna Endam MSc,

    1. Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada
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  • Abdelali Filali-Mouhim PhD,

    1. Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada
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  • Pierre Boisvert MD,

    1. Department of Otolaryngology, Saint-François d’Assise Hospital, Québec, QC, Canada
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  • Louis-Philippe Boulet MD,

    1. Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
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  • Marie-Eve Boulay MSc,

    1. Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
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  • Sophie Vallée-Smedja,

    1. Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada
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  • Yohan Bossé PhD,

    1. Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
    2. Department of Molecular Medicine, Laval University, Québec, QC, Canada
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  • Martin Desrosiers MD

    Corresponding author
    1. Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada
    2. Department of Otolaryngology-Head and Neck Surgery, Montreal General Hospital, McGill University, Montreal, QC, Canada
    • Correspondence to: Martin Desrosiers, MD, CHUM Hôtel-Dieu, 3840 St. Urbain Street, Montreal, QC, Canada H2W 1T8; e-mail: desrosiers_martin@hotmail.com

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  • Funding sources for the study: Fondation Antoine Turmel.

  • Potential conflict of interest: None provided.

  • C.C. and L.M.E. contributed equally to this work.

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.

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.

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