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Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation

Author

Listed:
  • Elmo C. Saarentaus

    (University of Helsinki
    University of Helsinki and Helsinki University Hospital)

  • Juha Karjalainen

    (University of Helsinki
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Joel T. Rämö

    (University of Helsinki
    Broad Institute of MIT and Harvard)

  • Tuomo Kiiskinen

    (University of Helsinki
    Finnish Institute for Health and Welfare)

  • Aki S. Havulinna

    (University of Helsinki
    Finnish Institute for Health and Welfare)

  • Juha Mehtonen

    (University of Helsinki)

  • Heidi Hautakangas

    (University of Helsinki)

  • Sanni Ruotsalainen

    (University of Helsinki)

  • Max Tamlander

    (University of Helsinki)

  • Nina Mars

    (University of Helsinki
    Broad Institute of MIT and Harvard)

  • Sanna Toppila-Salmi

    (Helsinki University Hospital and University of Helsinki)

  • Matti Pirinen

    (University of Helsinki
    University of Helsinki
    University of Helsinki)

  • Mitja Kurki

    (University of Helsinki
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Samuli Ripatti

    (University of Helsinki
    Broad Institute of MIT and Harvard
    University of Helsinki)

  • Mark Daly

    (University of Helsinki
    Massachusetts General Hospital
    Broad Institute of MIT and Harvard)

  • Tuula Palotie

    (University of Helsinki
    Helsinki University Hospital)

  • Antti Mäkitie

    (University of Helsinki and Helsinki University Hospital)

  • Aarno Palotie

    (University of Helsinki
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

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.

Suggested Citation

  • Elmo C. Saarentaus & Juha Karjalainen & Joel T. Rämö & Tuomo Kiiskinen & Aki S. Havulinna & Juha Mehtonen & Heidi Hautakangas & Sanni Ruotsalainen & Max Tamlander & Nina Mars & Sanna Toppila-Salmi & M, 2023. "Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-33626-w
    DOI: 10.1038/s41467-022-33626-w
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