A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02

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

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. More... »

PAGES

267-276

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0314-6

    DOI

    http://dx.doi.org/10.1038/s41588-018-0314-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111273886

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30643255


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