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

Elmo C Saarentaus; Juha Karjalainen; Joel T Rämö; Tuomo Kiiskinen; Aki S Havulinna; Juha Mehtonen; Heidi Hautakangas; Sanni Ruotsalainen; Max Tamlander; Nina Mars; FINNGEN; Sanna Toppila-Salmi; Matti Pirinen; Mitja Kurki; Samuli Ripatti; Mark Daly; Tuula Palotie; Antti Mäkitie; Aarno Palotie

doi:10.1038/s41467-022-33626-w

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

Nat Commun. 2023 Jan 18;14(1):83. doi: 10.1038/s41467-022-33626-w.

Authors

Elmo C Saarentaus^{1

2}, Juha Karjalainen^{1

3

4}, Joel T Rämö^{1

5}, Tuomo Kiiskinen^{1

6}, Aki S Havulinna^{1

6}, Juha Mehtonen¹, Heidi Hautakangas¹, Sanni Ruotsalainen¹, Max Tamlander¹, Nina Mars^{1

7}; FINNGEN; Sanna Toppila-Salmi⁸, Matti Pirinen^{1

9

10}, Mitja Kurki^{1

3

4}, Samuli Ripatti^{1

7

10}, Mark Daly^{1

4

7}, Tuula Palotie^{11

12}, Antti Mäkitie², Aarno Palotie^{13

14

15}

Affiliations

¹ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
² Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵ Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Finnish Institute for Health and Welfare, Helsinki, Finland.
⁷ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁹ Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
¹⁰ Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹¹ Orthodontics, Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹² Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland.
¹³ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. aarno.palotie@helsinki.fi.
¹⁴ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. aarno.palotie@helsinki.fi.
¹⁵ Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. aarno.palotie@helsinki.fi.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Asthma* / genetics
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Humans
Inflammation / genetics
Pharyngeal Diseases* / genetics
Polymorphism, Single Nucleotide
Respiration Disorders*

Abstract

Publication types

MeSH terms

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