Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation.
Nat Commun
; 14(1): 83, 2023 01 18.
Article
em En
| MEDLINE
| ID: mdl-36653354
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos Respiratórios
/
Asma
/
Doenças Faríngeas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Finlândia