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

L Paternoster, M Standl, CM Chen, A Ramasamy, K Bonnelykke, Liesbeth Duijts, MA Ferreira, AC Alves, JP Thyssen, E Albrecht, H Baurecht, BWA Feenstra, PMA Sleiman, P Hysi, NM Warrington, I Curjuric, R Myhre, JA Curtin, MM Groen-Blokhuis, M KerkhofA Saaf, A Franke, D Ellinghaus, R Folster-Holst, E Dermitzakis, SB Montgomery, H Prokisch, K Heim, AL Hartikainen, A Pouta, J Pekkanen, AIF Blakemore, JL Buxton, M Kaakinen, DL Duffy, PA Madden, AC Heath, GW Montgomery, PJ Thompson, MC Matheson, P Le Souef, B St Pourcain, GD Smith, J Henderson, JP Kemp, NJ Timpson, P Deloukas, SM Ring, HE Wichmann, M Muller-Nurasyid, N Novak, N Klopp, E Rodriguez, W McArdle, A Linneberg, T Menne, EA Nohr, Bert Hofman, André Uitterlinden, CM van Duijin, Fernando Rivadeneira, Johan Jongste, Ralf Valk, M Wjst, R Jogi, F Geller, HA Boyd, JC Murray, C Kim, F Mentch, M March, M Mangino, TD Spector, V Bataille, CE Pennell, PG Holt, P Sly, CMT Tiesler, E Thiering, T Illig, M Imboden, W Nystad, A Simpson, JJ (Jouke Jan) Hottenga, D Postma, GH Koppelman, HA Smit, C Soderhall, B Chawes, E Kreiner-Moller, H Bisgaard, E Melen, DI Boomsma, A Custovic, B Jacobsson, NM Probst-Hensch, LJ Palmer, D Glass, H Hakonarson, M Melbye, DL Jarvis, Vincent Jaddoe, C Gieger, DP Strachan, NG Martin, MR Jarvelin, J (Joachim) Heinrich, DM Evans, S Weidinger

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Abstract

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 x 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 x 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 x 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.
Original languageUndefined/Unknown
Pages (from-to)187-192
Number of pages6
JournalNature Genetics
Volume44
Issue number2
DOIs
Publication statusPublished - 2012

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