Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa
Jean Bousquet; Paula Kauppi; Tuomas Jartti; Annina Lyly; Matti Kankainen; Sanna Toppila-Salmi; Anu Laulajainen-Hongisto; Kati Donner; Pirkko Mattila; Kishor Dhaygude; Risto Renkonen; Tanzeela Hanif
Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa
Jean Bousquet
Paula Kauppi
Tuomas Jartti
Annina Lyly
Matti Kankainen
Sanna Toppila-Salmi
Anu Laulajainen-Hongisto
Kati Donner
Pirkko Mattila
Kishor Dhaygude
Risto Renkonen
Tanzeela Hanif
BMC
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042823504
https://urn.fi/URN:NBN:fi-fe2021042823504
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]