| Title: | A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis |
| Journal: | Nature Genetics |
| Published: | 14 Jan 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30643255/ |
| DOI: | https://doi.org/10.1038/s41588-018-0314-6 |
| Citations: | 95 (36 in last 2 years) as of 8 Aug 2024 |
Publication 3908
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Abstract
Nasal polyps (NP) are lesions on the nasal and paranasal sinus mucosa and are a risk factor for chronic rhinosinusitis (CRS). We performed genome-wide association studies on NP and CRS in Iceland and the UK (using UK Biobank data) with 4,366 NP cases, 5,608 CRS cases, and >700,000 controls. We found 10 markers associated with NP and 2 with CRS. We also tested 210 markers reported to associate with eosinophil count, yielding 17 additional NP associations. Of the 27 NP signals, 7 associate with CRS and 13 with asthma. Most notably, a missense variant in ALOX15 that causes a p.Thr560Met alteration in arachidonate 15-lipoxygenase (15-LO) confers large genome-wide significant protection against NP (P = 8.0 × 10−27, odds ratio = 0.32; 95% confidence interval = 0.26, 0.39) and CRS (P = 1.1 × 10−8, odds ratio = 0.64; 95% confidence interval = 0.55, 0.75). p.Thr560Met, carried by around 1 in 20 Europeans, was previously shown to cause near total loss of 15-LO enzymatic activity. Our findings identify 15-LO as a potential target for therapeutic intervention in NP and CRS.</p>
40 Authors
- Ragnar P. Kristjansson
- Stefania Benonisdottir
- Olafur B. Davidsson
- Asmundur Oddsson
- Vinicius Tragante
- Jon K. Sigurdsson
- Lilja Stefansdottir
- Stefan Jonsson
- Brynjar O. Jensson
- Joseph G. Arthur
- Gudny A. Arnadottir
- Gerald Sulem
- Bjarni V. Halldorsson
- Bjarni Gunnarsson
- Gisli H. Halldorsson
- Olafur A. Stefansson
- Gudjon R. Oskarsson
- Aimee M. Deaton
- Isleifur Olafsson
- Gudmundur I. Eyjolfsson
- Olof Sigurdardottir
- Pall T. Onundarson
- David Gislason
- Thorarinn Gislason
- Bjorn R. Ludviksson
- Dora Ludviksdottir
- Thorunn A. Olafsdottir
- Thorunn Rafnar
- Gisli Masson
- Florian Zink
- Gyda Bjornsdottir
- Olafur Th. Magnusson
- Unnur S. Bjornsdottir
- Gudmar Thorleifsson
- Gudmundur L. Norddahl
- Daniel F. Gudbjartsson
- Unnur Thorsteinsdottir
- Ingileif Jonsdottir
- Patrick Sulem
- Kari Stefansson
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