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

• Published in: Nature genetics Vol. 48; no. 11; pp. 1418 - 1424
• Main Authors: Jin, Ying, Andersen, Genevieve, Yorgov, Daniel, Ferrara, Tracey M, Ben, Songtao, Brownson, Kelly M, Holland, Paulene J, Birlea, Stanca A, Siebert, Janet, Hartmann, Anke, Lienert, Anne, van Geel, Nanja, Lambert, Jo, Luiten, Rosalie M, Wolkerstorfer, Albert, Wietze van der Veen, J P, Bennett, Dorothy C, Taïeb, Alain, Ezzedine, Khaled, Kemp, E Helen, Gawkrodger, David J, Weetman, Anthony P, Kõks, Sulev, Prans, Ele, Kingo, Külli, Karelson, Maire, Wallace, Margaret R, McCormack, Wayne T, Overbeck, Andreas, Moretti, Silvia, Colucci, Roberta, Picardo, Mauro, Silverberg, Nanette B, Olsson, Mats, Valle, Yan, Korobko, Igor, Böhm, Markus, Lim, Henry W, Hamzavi, Iltefat, Zhou, Li, Mi, Qing-Sheng, Fain, Pamela R, Santorico, Stephanie A, Spritz, Richard A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2016; Nature Publishing Group
• Subjects: 45/43; 45/77; 631/208/205/2138; 692/699/249/1313; Agriculture; Animal Genetics and Genomics; Antigens; Apoptosis; Autoimmune diseases; Autoimmune Diseases - genetics; Biomedicine; Cancer Research; Development and progression; Female; Gene expression; Gene Function; Gene mapping; Genealogy; Genetic aspects; Genetic Predisposition to Disease; Genetic variation; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Health aspects; Human Genetics; Humans; letter; Male; Melanoma; Melanoma - genetics; Meta-analysis; Methods; Proteins; Quantitative Trait Loci; Risk Assessment; Risk factors; Skin cancer; Skin diseases; Studies; Supercomputers; T cell receptors; Transcription factors; Vitiligo; Vitiligo - genetics
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3680

Richard Spritz and colleagues present a genome-wide association study of autoimmune vitiligo in 4,680 cases and 39,586 controls and report 23 new risk loci. Their results highlight specific pathways, including immune response, apoptosis and melanocyte function, that may be important in the pathobiology of autoimmune vitiligo. Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes 1 , with epidemiological association with other autoimmune diseases 2 . 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.