Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Nat Commun. 2023 Jan 18;14(1):83. doi: 10.1038/s41467-022-33626-w.
Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.
炎症和感染性上呼吸道疾病（ICD-10：J30-J39），如鼻-鼻窦、咽和喉疾病，是日益严重的健康问题，但它们的基因组相似性尚不清楚。我们对 260,405 名芬兰人基因研究参与者中的 8 种上呼吸道疾病（61,195 例）进行了全基因组关联分析，根据潜在的遗传相关结构对 4 组疾病进行了荟萃分析。为了了解哪些遗传位点导致上呼吸道疾病及其亚型易感性，我们检测到 41 个独立的全基因组显著位点，区分了对鼻-鼻窦疾病或咽疾病或两者的影响。精细映射提示 9 个基因中的非 synonymous 变异，包括与免疫相关疾病相关的 3 个基因。表型全基因组分析提示鼻-鼻窦疾病位点与哮喘和特应性皮炎相关，咽疾病位点与炎症性肠病和其他免疫介导性疾病相关。上呼吸道疾病也与类风湿关节炎、自身免疫性甲状腺功能减退症和银屑病等自身免疫性疾病存在遗传相关性。最后，我们关联了鼻-鼻窦和咽疾病中分别导致 2 型免疫反应的独立基因途径。我们表明，上呼吸道疾病之间存在共同的遗传易感性，这种易感性扩展到了多种机制的几种免疫介导性疾病，如 2 型高炎症。
