Genomics of asthma, allergy and chronic rhinosinusitis : novel concepts and relevance in airway mucosa

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Laulajainen-Hongisto , A , Lyly , A , Hanif , T , Dhaygude , K , Kankainen , M , Renkonen , R , Donner , K , Mattila , P , Jartti , T , Bousquet , J , Kauppi , P & Toppila-Salmi , S 2020 , ' Genomics of asthma, allergy and chronic rhinosinusitis : novel concepts and relevance in airway mucosa ' , Clinical and Translational Allergy , vol. 10 , no. 1 , 45 . https://doi.org/10.1186/s13601-020-00347-6

Title: Genomics of asthma, allergy and chronic rhinosinusitis : novel concepts and relevance in airway mucosa
Author: Laulajainen-Hongisto, Anu; Lyly, Annina; Hanif, Tanzeela; Dhaygude, Kishor; Kankainen, Matti; Renkonen, Risto; Donner, Kati; Mattila, Pirkko; Jartti, Tuomas; Bousquet, Jean; Kauppi, Paula; Toppila-Salmi, Sanna
Contributor: University of Helsinki, HUS Head and Neck Center
University of Helsinki, Clinicum
University of Helsinki, Department of Pathology
University of Helsinki, Department of Pathology
University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
University of Helsinki, HUS Comprehensive Cancer Center
University of Helsinki, Hematologian yksikkö
University of Helsinki, HUS Inflammation Center
University of Helsinki, HUS Inflammation Center
Date: 2020-10-28
Language: eng
Number of pages: 17
Belongs to series: Clinical and Translational Allergy
ISSN: 2045-7022
URI: http://hdl.handle.net/10138/321952
Abstract: Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p <10(-8)) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p <0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p <0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
Subject: Asthma
Allergic rhinitis
Airway epithelium
GWAS
Gene ontology
Pathway
WIDE ASSOCIATION
INCREASES SUSCEPTIBILITY
GENOMEWIDE ASSOCIATION
ATOPIC-DERMATITIS
CHILDHOOD ASTHMA
HAY-FEVER
LUNG
EXPRESSION
NASAL
RISK
3121 General medicine, internal medicine and other clinical medicine
3125 Otorhinolaryngology, ophthalmology
3111 Biomedicine
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