Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.
Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.
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DOI：
10.1038/ng.3680
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发表时间：
2016-11
期刊：
影响因子：
30.8
通讯作者：
Spritz, Richard A.
中科院分区：
文献类型：
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作者：
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;van der Veen, J. P. Wietze;Bennett, Dorothy C.;Taieb, Alain;Ezzedine, Khaled;Kemp, E. Helen;Gawkrodger, David J.;Weetman, Anthony P.;Koks, Sulev;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.;Spritz, Richard A.
白癜风是一种自身免疫性疾病，皮肤色素脱失是由黑素细胞破坏引起的，与其他自身免疫性疾病有流行病学联系。在先前的连锁和全基因组关联研究(GWAS1，GWAS2)中，我们在欧洲人(EUR)血统的患者中发现了27个白癜风易感基因。我们在EUR受试者中进行了第三次GWAS3(GWAS3)，增加了GWAS1和GWAS2对照，全基因组归因，并对所有三个GWASs进行了荟萃分析，然后进行了独立的复制。对4680例患者和39586名对照进行的联合分析发现了23个新基因座和7个暗示基因座，其中大多数编码免疫和凋亡调节因子，一些还与其他自身免疫性疾病有关，以及几个黑素细胞调节因子。生物信息学分析表明，因果调控变异占主导地位，其中一些对应于这些基因座上的eQTL。总之，已识别的基因为白癜风的遗传结构和病理生物学提供了一个框架，突出了与其他自身免疫性疾病和黑色素瘤的关系，并提供了潜在的治疗靶点。
Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes, with epidemiologic association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR 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 loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment.
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