| Literature DB >> 30643255 |
Ragnar P Kristjansson1, Stefania Benonisdottir1, Olafur B Davidsson1, Asmundur Oddsson1, Vinicius Tragante1,2, Jon K Sigurdsson1, Lilja Stefansdottir1, Stefan Jonsson1, Brynjar O Jensson1, Joseph G Arthur1, Gudny A Arnadottir1, Gerald Sulem1, Bjarni V Halldorsson1,3, Bjarni Gunnarsson1, Gisli H Halldorsson1, Olafur A Stefansson1, Gudjon R Oskarsson1, Aimee M Deaton1, Isleifur Olafsson4, Gudmundur I Eyjolfsson5, Olof Sigurdardottir6, Pall T Onundarson7,8, David Gislason7,9, Thorarinn Gislason7,10, Bjorn R Ludviksson7,11, Dora Ludviksdottir7,12, Thorunn A Olafsdottir1,7, Thorunn Rafnar1, Gisli Masson1, Florian Zink1, Gyda Bjornsdottir1, Olafur Th Magnusson1, Unnur S Bjornsdottir9,13, Gudmar Thorleifsson1, Gudmundur L Norddahl1, Daniel F Gudbjartsson1,14, Unnur Thorsteinsdottir1,7, Ingileif Jonsdottir1,7, Patrick Sulem15, Kari Stefansson16,17.
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.Entities:
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Year: 2019 PMID： 30643255 DOI： 10.1038/s41588-018-0314-6
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330