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Kristjansson, Ragnar P; Benonisdottir, Stefania; Davidsson, Olafur B; Oddsson, Asmundur; Tragante, Vinicius; Sigurdsson, Jon K; Stefansdottir, Lilja; Jonsson, Stefan; Jensson, Brynjar O; Arthur, Joseph G; Arnadottir, Gudny A; Sulem, Gerald; Halldorsson, Bjarni V; Gunnarsson, Bjarni; Halldorsson, Gisli H; Stefansson, Olafur A; Oskarsson, Gudjon R; Deaton, Aimee M; Olafsson, Isleifur; Eyjolfsson, Gudmundur I; Sigurdardottir, Olof; Onundarson, Pall T; Gislason, David; Gislason, Thorarinn; Ludviksson, Bjorn R; Ludviksdottir, Dora; Olafsdottir, Thorunn A; Rafnar, Thorunn; Masson, Gisli; Zink, Florian; Bjornsdottir, Gyda; Magnusson, Olafur Th; Bjornsdottir, Unnur S; Thorleifsson, Gudmar; Norddahl, Gudmundur L; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Jonsdottir, Ingileif; Sulem, Patrick; Stefansson, Kari
Nature genetics, 02/2019, Letnik: 51, Številka: 2Journal Article
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 , odds ratio = 0.32; 95% confidence interval = 0.26, 0.39) and CRS (P = 1.1 × 10 , 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.
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