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Genome-wide association analysis identifies three psoriasis susceptibility loci

To identify novel psoriasis susceptibility loci, we carried out a meta-analysis of two recent genome-wide association studies 1,2, yielding a discovery sample of 1,831 cases and 2,546 controls. 102 of the most promising loci in the discovery analysis were followed up in a three-stage replication stu...

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Detalles Bibliográficos
Autores principales: Stuart, Philip E., Nair, Rajan P., Ellinghaus, Eva, Ding, Jun, Tejasvi, Trilokraj, Gudjonsson, Johann E., Li, Yun, Weidinger, Stephan, Eberlein, Bernadette, Gieger, Christian, Wichmann, H. Erich, Kunz, Manfred, Ike, Robert, Krueger, Gerald G., Bowcock, Anne M., Mroweitz, Ulrich, Lim, Henry W., Voorhees, John J., Abecasis, Goncalo R., Weichenthal, Michael, Franke, Andre, Rahman, Proton, Gladman, Dafna D., Elder, James T.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965799/
https://www.ncbi.nlm.nih.gov/pubmed/20953189
http://dx.doi.org/10.1038/ng.693
Descripción
Sumario:To identify novel psoriasis susceptibility loci, we carried out a meta-analysis of two recent genome-wide association studies 1,2, yielding a discovery sample of 1,831 cases and 2,546 controls. 102 of the most promising loci in the discovery analysis were followed up in a three-stage replication study using 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland, and Germany. Association at a genome-wide level of significance for the combined discovery and replication samples was found for three genomic regions. One contains NOS2 (rs4795067, p = 4 × 10(−11)), another contains FBXL19 (rs10782001, p = 9 × 10(−10)), and a third contains PSMA6 and NFKBIA (rs12586317, p = 2 × 10(−8)). All three loci were also strongly associated with the subphenotypes of psoriatic arthritis and purely cutaneous psoriasis. Finally, we confirmed a recently identified3 association signal near RNF114.