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

Collapse authors list.
Jin, Ying, Andersen, Genevieve, Yorgov, Daniel, Ferrara, Tracey M, Ben, Songtao, Brownson, Kelly M, Holland, Paulene J, Birlea, Stanca A, Siebert, Janet, Hartmann, Anke et al (show 34 more authors) , Lienert, Anne, van Geel, Nanja, Lambert, Jo, Luiten, Rosalie M, Wolkerstorfer, Albert, van der Veen, JP Wietze, Bennett, Dorothy C, Taieb, Alain, Ezzedine, Khaled, Kemp, E Helen, Gawkrodger, David J, Weetman, Anthony P, Koks, Sulev ORCID: 0000-0001-6087-6643, Prans, Ele, Kingo, Kulli, 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, Boehm, Markus, Lim, Henry W, Hamzavi, Iltefat, Zhou, Li, Mi, Qing-Sheng, Fain, Pamela R, Santorico, Stephanie A and Spritz, Richard 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). pp. 1418-1424.

Text Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.pdf - Published version Download (1MB)

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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Melanoma, Vitiligo, Autoimmune Diseases, Genetic Predisposition to Disease, Risk Assessment, Genotype, Quantitative Trait Loci, Female, Male, Genome-Wide Association Study
Depositing User:	Symplectic Admin
Date Deposited:	17 Jul 2017 08:46
Last Modified:	19 Jan 2023 06:59
DOI:	10.1038/ng.3680
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008502