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A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis.

Artikel i vetenskaplig tidskrift
Författare Anton Bohman
Julius Juodakis
Martin Oscarsson
Jonas Bacelis
Mats Bende
Åsa Torinsson Naluai
Publicerad i PloS one
Volym 12
Nummer/häfte 12
Sidor e0185244
ISSN 1932-6203
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi
Sidor e0185244
Språk en
Länkar dx.doi.org/10.1371/journal.pone.018...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Chronic Disease, Family, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Nasal Polyps, complications, genetics, Polymorphism, Single Nucleotide, genetics, Quantitative Trait Loci, genetics, Rhinitis, complications, genetics, Sinusitis, complications, genetics
Ämneskategorier Oto-rino-laryngologi

Sammanfattning

The pathogenesis of chronic rhinosinusitis with nasal polyps is largely unknown. Previous studies have given valuable information about genetic variants associated with this disease but much is still unexplained. Our goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study.427 patients (293 males and 134 females) with CRSwNP and 393 controls (175 males and 218 females) were recruited from several Swedish hospitals. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX). Analyses of pathway enrichment, gene expression levels and expression quantitative trait loci were then performed in turn.None of the analysed SNPs reached genome wide significant association of 5.0 x 10-8. Pathway analyses using our top 1000 markers with the most significant association p-values resulted in 138 target genes. A comparison between our target genes and gene expression data from the NCBI Gene Expression Omnibus database showed significant overlap for 36 of these genes. Comparisons with data from expression quantitative trait loci showed the most skewed allelic distributions in cases with chronic rhinosinusitis with nasal polyps compared with controls for the genes HLCS, HLA-DRA, BICD2, VSIR and SLC5A1.Our study indicates that HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 could be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. HLA-DRA has been associated with chronic rhinosinusitis with nasal polyps in previous studies and HLCS, BICD2, VSIR and SLC5A1 may be new targets for future research.

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