| Title: | 131 genetic loci highlight immunological pathways and tissues in nasal polyposis and asthma |
| Journal: | Nature Communications |
| Published: | 10 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41213931/ |
| DOI: | https://doi.org/10.1038/s41467-025-64847-4 |
| URL: | https://www.nature.com/articles/s41467-025-64847-4.pdf |
Publication 18973
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Abstract
The coexistence of asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with allergic phenotypes, disease severity and failure of first-line treatment for both asthma and CRSwNP. Recent studies have highlighted shared genetic components for these diseases. To better understand this shared component, we perform genome-wide meta-analyses of asthma (n = 71,481), CRSwNP (n = 9626) and chronic rhinosinusitis without nasal polyposis (CRSsNP, n = 15,448) in FinnGen and UKB (685,602 controls). We detect 131 genomic associations, including 17 novel loci for asthma, 33 novel loci for CRSwNP, and one for CRSsNP. A shared impact on asthma and CRSwNP is observed at 71 loci. A cross-trait meta-analysis using all disorders further implicates 17 loci associated with asthma or asthma and CRSwNP. We also find 17 nonsynonymous associating variants, including a novel TP63 missense variant association with CRSwNP (OR = 1.519 [1.331-1.734]). Gene set analyses confirm enrichment of genes involved with type 2 inflammation, Jak-STAT signaling, and FOXP3 signaling. Our results highlight new shared and separate genetic pathways for CRSwNP and asthma. These provide several avenues of further investigation in functional and epidemiological follow-up, and evidence for immunological and non-immunological mechanisms behind both diseases.</p>
11 Keywords
- Asthma
- Chronic Disease
- Forkhead Transcription Factors
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Nasal Polyps
- Polymorphism, Single Nucleotide
- Rhinosinusitis
- Signal Transduction
11 Authors
- Elmo C. Saarentaus
- Kasper Fischer-Rasmussen
- Eeva Sliz
- Argyro Bizaki-Vallaskangas
- Tarja Laitinen
- Sanna Toppila-Salmi
- Hannu Kankaanranta
- Johannes Kettunen
- Klaus Bønnelykke
- Aarno Palotie
- Antti Mäkitie
1 Application
| Application ID | Title |
|---|---|
| 54273 | Elucidating the genetic architecture and shared origins of chronic inflammatory diseases |
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