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Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

journal contribution
posted on 2022-10-24, 05:19 authored by L Paternoster, M Standl, C M Chen, A Ramasamy, K Bøpnnelykke, L Duijts, M A Ferreira, A C Alves, J P Thyssen, E Albrecht, H Baurecht, B Feenstra, P M A Sleiman, P Hysi, N M Warrington, I Curjuric, R Myhre, J A Curtin, M M Groen-Blokhuis, M Kerkhof, A Sääf, A Franke, D Ellinghaus, R Fölster-Holst, E Dermitzakis, S B Montgomery, H Prokisch, K Heim, A L Hartikainen, A Pouta, J Pekkanen, A I F Blakemore, J L Buxton, M Kaakinen, D L Duffy, P A Madden, A C Heath, G W Montgomery, P J Thompson, M C Matheson, P Le Souëf, B S Pourcain, G D Smith, J Henderson, J P Kemp, N J Timpson, P Deloukas, S M Ring, H E Wichmann, M Müller-Nurasyid, N Novak, N Klopp, E Rodríguez, W McArdle, A Linneberg, T Menné, E A Nohr, A Hofman, A G Uitterlinden, C M Van Duijn, F Rivadeneira, J C De Jongste, R J P Van Der Valk, M Wjst, R Jogi, F Geller, H A Boyd, J C Murray, C Kim, F Mentch, M March, M Mangino, T D Spector, V Bataille, C E Pennell, P G Holt, Peter SlyPeter Sly, C M T Tiesler, E Thiering, T Illig, M Imboden, W Nystad, A Simpson, J J Hottenga, D Postma, G H Koppelman, H A Smit, C Söderhäll, B Chawes, E Kreiner-Møpller, H Bisgaard, E Melén, D I Boomsma, A Custovic, B Jacobsson, N M Probst-Hensch, L J Palmer, D Glass, H Hakonarson, M Melbye
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10 -13) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10 -9), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10 -8). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis. © 2012 Nature America, Inc. All rights reserved.



Nature Genetics




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