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
Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Kasarmikatu 11-13, P.O.Box 263, 00029 HUS Helsinki, Finland.
Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.
Clin Transl Allergy. 2020 Oct 28;10(1):45. doi: 10.1186/s13601-020-00347-6. eCollection 2020.
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) 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.
全基因组关联研究(GWAS)已经揭示了多个与气道疾病相关的风险位点。然而,它们在哮喘、过敏性鼻炎(AR)或慢性鼻-鼻窦炎(CRS)发病中的作用尚未完全明确。本综述旨在评估GWAS研究中所确定的位点和基因与气道的相关性。我们从数据库中检索了GWAS,并创建了一份与哮喘、AR和CRS显著相关(p < 10)的位点列表。这一检索共从31项GWAS中得到了267个与哮喘/AR显著相关的位点。在此次检索中未发现与CRS相关的显著位点。共有170个蛋白质编码基因与这些位点相关。其中,76/170(44%)在人类蛋白质图谱(HPA)的染色显微镜图像中显示支气管上皮蛋白表达,61/170(36%)有关于具有气道上皮功能的文献报道。进行了基因本体(GO)和京都基因与基因组百科全书(KEGG)注释分析,发现19个功能蛋白类别在这些基因中显著富集(p < 0.05)。这些类别与细胞因子产生、细胞活化和适应性免疫反应相关,并且在网络分析中都紧密相连。我们还确定了15条在这些基因中显著富集(p < 0.05)的蛋白质通路,与辅助性T细胞分化、病毒感染、JAK-STAT信号通路和哮喘相关。根据我们的数据库和文献检索,哮喘或AR的三分之一GWAS水平风险位点基因似乎具有气道上皮功能。此外,许多风险位点基因与免疫相关。一些风险位点基因还与代谢、神经-肌肉骨骼或其他功能相关。在我们的通路分析中,这些功能相互重叠并形成了一个强大的网络,值得未来进行生物标志物和治疗学研究。
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