Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
Paternoster, L. and Standl, M. and Chen, C. M. and Ramasamy, A. and Bonnelykke, K. and Duijts, L. and Ferreira, M. A. and Alves, A. C. and Thyssen, J. P. and Albrecht, E. and Baurecht, H. and Feenstra, B. and Sleiman, P. M. and Hysi, P. and Warrington, N. M. and Curjuric, I. and Myhre, R. and Curtin, J. A. and Groen-Blokhuis, M. M. and Kerkhof, M. and Saaf, A. and Franke, A. and Ellinghaus, D. and Folster-Holst, R. and Dermitzakis, E. and Montgomery, S. B. and Prokisch, H. and Heim, K. and Hartikainen, A. L. and Pouta, A. and Pekkanen, J. and Blakemore, A. I. and Buxton, J. L. and Kaakinen, M. and Duffy, D. L. and Madden, P. A. and Heath, A. C. and Montgomery, G. W. and Thompson, P. J. and Matheson, M. C. and Le, S. P. and Pourcain, B. S. and Smith, G. D. and Henderson, J. and Kemp, J. P. and Timpson, N. J. and Deloukas, P. and Ring, S. M. and Wichmann, H. E. and Muller-Nurasyid, M. and Novak, N. and Klopp, N. and Rodriguez, E. and McArdle, W. and Linneberg, A. and Menne, T. and Nohr, E. A. and Hofman, A. and Uitterlinden, A. G. and van Duijn, C. M. and Rivadeneira, F. and de Jongste, J. C. and van der Valk, R. J. and Wjst, M. and Jogi, R. and Geller, F. and Boyd, H. A. and Murray, J. C. and Kim, C. and Mentch, F. and March, M. and Mangino, M. and Spector, T. D. and Bataille, V. and Pennell, C. E. and Holt, P. G. and Sly, P. and Tiesler, C. M. and Thiering, E. and Illig, T. and Imboden, M. and Nystad, W. and Simpson, A. and Hottenga, J. J. and Postma, D. and Koppelman, G. H. and Smit, H. A. and Soderhall, C. and Chawes, B. and Kreiner-Moller, E. and Bisgaard, H. and Melen, E. and Boomsma, D. I. and Custovic, A. and Jacobsson, B. and Probst-Hensch, N. M. and Palmer, L. J. and Glass, D. and Hakonarson, H. and Melbye, M. and Jarvis, D. L. and Jaddoe, V. W. and Gieger, C. and Strachan, D. P. and Martin, N. G. and Jarvelin, M. R. and Heinrich, J. and Evans, D. M. and Weidinger, S.. (2012) Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature genetics, Vol. 44, H. 2. pp. 187-192.
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
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology
Curjuric, Ivan
Article, refereed
Nature Publ
doi: 10.1038/ng.1017