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

• Published in: Nature genetics Vol. 44; no. 2; pp. 187 - 192
• Main Authors: 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 M A, Warrington, Nicole M, Curjuric, Ivan, Myhre, Ronny, Curtin, John A, Groen-Blokhuis, Maria M, Kerkhof, Marjan, 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 I F, Buxton, Jessica L, Duffy, David L, Madden, Pamela A, Montgomery, Grant W, Matheson, Melanie C, Le Souëf, Peter, Pourcain, Beate St, Smith, George Davey, Henderson, John, 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 J P, Wjst, Matthias, Jogi, Rain, Geller, Frank, Boyd, Heather A, Murray, Jeffrey C, Mentch, Frank, March, Michael, Mangino, Massimo, Spector, Tim D, Bataille, Veronique, Pennell, Craig E, Holt, Patrick G, Sly, Peter, Tiesler, Carla M T, 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, Palmer, Lyle J, Glass, Daniel, Hakonarson, Hakon, Melbye, Mads, Jarvis, Deborah L, Jaddoe, Vincent W V, Gieger, Christian, Strachan, David P, Martin, Nicholas G, Jarvelin, Marjo-Riitta, Heinrich, Joachim, Evans, David M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2012; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/727/2000; 692/699/249/2510/1415; 692/700/478/174; Agriculture; Allergic diseases; Allergies; Animal Genetics and Genomics; Asthma; Atopic dermatitis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Differentiation - genetics; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 20 - genetics; Chromosomes, Human, Pair 5; Clinical Medicine; Confidence intervals; Cytokines - genetics; Dermatitis; Dermatitis, Atopic - genetics; Dermatitis, Atopic - immunology; DNA-Binding Proteins - genetics; Epidermis - immunology; Female; Filaggrin Proteins; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetic susceptibility; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Human Genetics; Humans; Immunopathology; Intermediate Filament Proteins - genetics; Kinesins - genetics; Klinisk medicin; letter; Male; Medical sciences; Medicin och hälsovetenskap; Meta-analysis; Mutation; Polymorphism, Single Nucleotide; Quantitative trait loci; Risk; Risk factors; Skin allergic diseases. Stinging insect allergies; Skin diseases; Transcription Factors - genetics; Allergy; Immunopathology; Skin disease; Association; Atopic dermatitis; Risk; Identification; Locus; Atopy; Metaanalysis
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.1017

Lavinia Paternoster and colleagues report a meta-analysis of genome-wide association studies of atopic dermatitis. They report three newly identified associated loci near OVOL1 and ACTL9 and in KIF3A . 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.