META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES IDENTIFIES THREE NEW RISK LOCI FOR ATOPIC DERMATITIS

Atopic dermatitis (AD) is a common chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing AD are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 cases and 20,565 controls from 16 population-based cohorts and followed up the ten m...

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Detalles Bibliográficos
Autores principales: Paternoster, Lavinia, Standl, Marie, Chen, Chih-Mei, Ramasamy, Adaikalavan, Bønnelykke, Klaus, Duijts, Liesbeth, Ferreira, Manuel A, Alves, Alexessander Couto, Thyssen, Jacob P, Albrecht, Eva, Baurecht, Hansjörg, Feenstra, Bjarke, Sleiman, Patrick MA, Hysi, Pirro, Warrington, Nicole M, Curjuric, Ivan, Myhre, Ronny, Curtin, John A, Groen-Blokhuis, Maria M, Kerkhof, Marjan, Sääf, Annika, Franke, Andre, Ellinghaus, David, Fölster-Holst, Regina, Dermitzakis, Emmanouil, Montgomery, Stephen B, Prokisch, Holger, Heim, Katharina, Hartikainen, Anna-Liisa, Pouta, Anneli, Pekkanen, Juha, Blakemore, Alexandra IF, Buxton, Jessica L, Kaakinen, Marika, Duffy, David L, Madden, Pamela A, Heath, Andrew C, Montgomery, Grant W, Thompson, Philip J, Matheson, Melanie C, Le Souëf, Peter, Pourcain, Beate St, Smith, George Davey, Henderson, John, Kemp, John P, Timpson, Nicholas J, Deloukas, Panos, Ring, Susan M, Wichmann, H-Erich, Müller-Nurasyid, Martina, Novak, Natalija, Klopp, Norman, Rodríguez, Elke, McArdle, Wendy, Linneberg, Allan, Menné, Torkil, Nohr, Ellen A, Hofman, Albert, Uitterlinden, André G, van Duijn, Cornélia M, Rivadeneira, Fernando, de Jongste, Johan C, van der Valk, Ralf JP, Wjst, Matthias, Jogi, Rain, Geller, Frank, Boyd, Heather A, Murray, Jeffrey C, Kim, Cecilia, Mentch, Frank, March, Michael, Mangino, Massimo, Spector, Tim D, Bataille, Veronique, Pennell, Craig E, Holt, Patrick G, Sly, Peter, Tiesler, Carla MT, Thiering, Elisabeth, Illig, Thomas, Imboden, Medea, Nystad, Wenche, Simpson, Angela, Hottenga, Jouke-Jan, Postma, Dirkje, Koppelman, Gerard H, Smit, Henriette A, Söderhäll, Cilla, Chawes, Bo, Kreiner-Møller, Eskil, Bisgaard, Hans, Melén, Erik, Boomsma, Dorret I, Custovic, Adnan, Jacobsson, Bo, Probst-Hensch, Nicole M, Palmer, Lyle J, Glass, Daniel, Hakonarson, Hakon, Melbye, Mads, Jarvis, Deborah L, Jaddoe, Vincent WV, Gieger, Christian, Strachan, David P, Martin, Nicholas G, Jarvelin, Marjo-Riitta, Heinrich, Joachim, Evans, David M, Weidinger, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272375/
https://www.ncbi.nlm.nih.gov/pubmed/22197932
http://dx.doi.org/10.1038/ng.1017
Descripción
Sumario:Atopic dermatitis (AD) is a common chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing AD are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 cases and 20,565 controls from 16 population-based cohorts and followed up the ten most strongly associated novel markers in a further 5,419 cases and 19,833 controls from 14 studies. Three SNPs met genome-wide significance in the discovery and replication cohorts combined: rs479844 upstream of OVOL1 (OR=0.88, p=1.1×10(−13)) and rs2164983 near ACTL9 (OR=1.16, p=7.1×10(−9)), genes which have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster on 5q31.1 (OR=1.11, p=3.8×10(−8)). We also replicated the FLG locus and two recently identified association signals at 11q13.5 (rs7927894, p=0.008) and 20q13.3 (rs6010620, p=0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in AD pathogenesis.

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