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

Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, Holland PJ, Birlea SA, Siebert J, Hartmann A, Lienert AM, Van Geel N, Lambert J, Luiten RM, Wolkerstorfer A, Van Der Veen JPW, Bennett DC, Taieb A, Ezzedine K, Kemp EH, Gawkrodger DJ, Weetman AP, Koks S, Prans E, Kingo K, Karelson M, Wallace MR, Mccormack WT, Overbeck A, Moretti S, Colucci R, Picardo M, Silverberg NB, Olsson M, Valle Y, Korobko I, Boehm M, Lim HW, Hamzavi I, Zhou L, Mi QS, Fain PR, Santorico SA, Spritz RA (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 48

Pages Range: 1418-1424

Journal Issue: 11

DOI: 10.1038/ng.3680

Abstract

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.

Authors with CRIS profile

Involved external institutions

CytoAnalytics Inc. United States (USA) (US) University Hospital Ghent Belgium (BE) University of Florida United States (USA) (US) University of Colorado System United States (USA) (US) Henry Ford Health System (HFHS) United States (USA) (US) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Vitiligo Research Foundation United States (USA) (US) International Vitiligo Center Sweden (SE) Columbia University United States (USA) (US) San Gallicano Dermatological Institute, IRCCS (ISG) Italy (IT) Università degli Studi di Firenze / University of Florence Italy (IT) Lumiderm Spain (ES) University of Tartu Estonia (EE) University of Sheffield United Kingdom (GB) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux France (FR) St George's, University of London (SGUL) / St George's Hospital Medical School United Kingdom (GB) University of Amsterdam Netherlands (NL)

How to cite

APA:

Jin, Y., Andersen, G., Yorgov, D., Ferrara, T.M., Ben, S., Brownson, K.M.,... Spritz, R.A. (2016). Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nature Genetics, 48(11), 1418-1424. https://dx.doi.org/10.1038/ng.3680

MLA:

Jin, Ying, et al. "Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants." Nature Genetics 48.11 (2016): 1418-1424.

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