Portal de Periódicos da CAPES

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

2016; Nature Portfolio; Volume: 48; Issue: 11 Linguagem: Inglês

10.1038/ng.3680

1546-1718

Ying Jin, Genevieve Andersen, Daniel Yorgov, Tracey M. Ferrara, Songtao Ben, Kelly M Brownson, Paulene J. Holland, Stanca A. Birlea, Janet Siebert, Anke Hartmann, Anne Lienert, Nanja van Geel, Jo Lambert, Rosalie M. Luiten, Albert Wolkerstorfer, J.P.W. van der Veen, Dorothy C. Bennett, Alain Taı̈eb, Khaled Ezzedine, E. Helen Kemp, David J. Gawkrodger, Anthony P. Weetman, Sulev Kõks, Ele Prans, Külli Kingo, Maire Karelson, Margaret R. Wallace, Wayne T. McCormack, Andreas Overbeck, Silvia Moretti, Roberta Colucci, Mauro Picardo, Nanette B. Silverberg, Mats J. Olsson, Yan Valle, И. В. Коробко, Markus Böhm, Henry W. Lim, Iltefat Hamzavi, Li Zhou, Qing‐Sheng Mi, Pamela R. Fain, Stephanie A. Santorico, Richard A. Spritz,

T-cell and B-cell Immunology

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.