Title

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

Author(s)

Y Jin, University of Colorado
G Andersen, University of Colorado
Daniel Yorgov, Indiana University - Purdue University Fort WayneFollow
T M. Ferrara, University of Colorado
S Ben, University of Colorado
K M. Brownson, University of Colorado
P J. Holland, University of Colorado
S A. Birlea, University of Colorado
J Siebert, CytoAnalytics
A Hartmann, University Hospital Erlangen
A Lienert, University Hospital Erlangen
N Van Geel, Ghent University Hospital
J Lambert, Ghent University Hospital
R M. Luiten, University of Amsterdam
A Wolkerstorfer, University of Amsterdam
J P. Wietze Van Der Veen, University of Amsterdam
D C. Bennett, University of London
A Taieb, Hôpital St.-André
K Ezzedine, Hôpital St.-André
E H. Kemp, University of Sheffield
D J. Gawkrodger, University of Sheffield
A P. Weetman, University of Sheffield
S Koks, University of Tartu
E Prans, University of Tartu
K Kingo, University of Tartu
M Karelson, University of Tartu
M R. Wallace, University of Florida
W T. McCormack, University of Florida
A Overbeck, Lumiderm
S Moretti, University of Florence
R Colucci, University of Florence
M Picardo, Istituto Dermatologico San Gallicano
N B. Silverberg, Columbia University
M Olsson, International Vitiligo Center
Y Valle, Vitiligo Research Foundation
I Korobko, Vitiligo Research Foundation
M Bohm, University of Münster
H W. Lim, Henry Ford Hospital
I Hamzavi, Henry Ford Hospital
L Zhou, Henry Ford Hospital
Q S. Mi, Henry Ford Hospital
P R. Fain, University of Colorado
S A. Santorico, University of Colorado
R A. Spritz, University of Colorado

Document Type

Article

Publication Date

11-2016

Publication Source

Nature Genetics

Volume

48

Issue

11

Inclusive pages

1418-1424

DOI

10.1038/ng.3680

Publisher

Nature Publishing Group

ISBN/ISSN

1061-4036

Peer Reviewed

yes

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.

Disciplines

Mathematics

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