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Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
Open accessAbstract
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.
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Metadata
- Authors
- Australian Asthma Genetics Consortium (AAGC), Paternoster, L., The Genetics of Overweight Young Adults (GOYA) Consortium, the EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium, Standl, M., Chen, C.-M., Ramasamy, A., Bønnelykke, K., Duijts, L., Ferreira, M. A., Alves, A. C., Thyssen, J. P., Albrecht, E., Baurecht, H., Feenstra, B., Sleiman, P. M. A., Hysi, P., Warrington, N. M., Curjuric, I., Myhre, R., Curtin, J. A., Groen-Blokhuis, M. M., Kerkhof, M., Sääf, A., Franke, A., Ellinghaus, D., Fölster-Holst, R., Dermitzakis, E., Montgomery, S. B., Prokisch, H., Heim, K., Hartikainen, A.-L., Pouta, A., Pekkanen, J., Blakemore, A. I. F., Buxton, J. L., Kaakinen, M., Duffy, D. L., Madden, P. A., Heath, A. C., Montgomery, G. W., Thompson, P. J., Matheson, M. C., Le Souëf, P., Pourcain, B. S., Smith, G. D., Henderson, J., Kemp, J. P., Timpson, N. J., Deloukas, P., Ring, S. M., Wichmann, H.-E., Müller-Nurasyid, M., Novak, N., Klopp, N., Rodríguez, E., McArdle, W., Linneberg, A., Menné, T., Nohr, E. A., Hofman, A., Uitterlinden, A. G., van Duijn, C. M., Rivadeneira, F., de Jongste, J. C., van der Valk, R. J. P., Wjst, M., Jogi, R., Geller, F., Boyd, H. A., Murray, J. C., Kim, C., Mentch, F., March, M., Mangino, M., Spector, T. D., Bataille, V., Pennell, C. E., Holt, P. G., Sly, P., Tiesler, C. M. T., Thiering, E., Illig, T., Imboden, M., Nystad, W., Simpson, A., Hottenga, J.-J., Postma, D., Koppelman, G. H., Smit, H. A., Söderhäll, C., Chawes, B., Kreiner-Møller, E., Bisgaard, H., Melén, E., Boomsma, D. I., Custovic, A., Jacobsson, B., Probst-Hensch, N. M., Palmer, L. J., Glass, D., Hakonarson, H., Melbye, M., Jarvis, D. L., Jaddoe, V. W. V., Gieger, C., Strachan, D. P., Martin, N. G., Jarvelin, M.-R., Heinrich, J., & Evans, D. M.
- Venue
- Nature Genetics
- Published
- 2011-12-25
- Volume
- 44
- Issue
- 2
- Pages
- 187-192
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1999690368
- Cited by
- 349
- References
- 89
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Australian Asthma Genetics Consortium (AAGC), Paternoster, L., The Genetics of Overweight Young Adults (GOYA) Consortium, the EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium, Standl, M., Chen, C.-M., Ramasamy, A., Bønnelykke, K., Duijts, L., Ferreira, M. A., Alves, A. C., Thyssen, J. P., Albrecht, E., Baurecht, H., Feenstra, B., Sleiman, P. M. A., Hysi, P., Warrington, N. M., Curjuric, I., . . . Evans, D. M. (2012). Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature Genetics. https://doi.org/10.1038/ng.1017
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