Vitiligo is an autoimmune disease in which destruction of skin melanocytes results in patches of white skin and hair. Genome-wide linkage studies and genome-wide association studies in European ancestry cases identified over 50 vitiligo susceptibility loci, defining a model of melanocyte-directed autoimmunity. Vitiligo heritability is exceedingly high, ~2/3 coming from common and ~1/3 from rare genomic variants; ~20% of vitiligo risk is environmental. Vitiligo genetic risk is polygenic, with greater additive risk in multiplex vitiligo families than simplex cases. Vitiligo age-of-onset is bimodal, also involving a major genetic component; a MHC enhancer haplotype confers extreme risk for vitiligo (OR 8.1) and early disease onset, increasing expression of HLA-DQB1 mRNA and HLA-DQ protein and thus perhaps facilitating presentation of triggering antigens. Vitiligo triggering also involves a major environmental component; dramatic delay in vitiligo age-of-onset, especially from 1973 to 2004, suggests that exposure or response to a key vitiligo environmental trigger diminished during this period. Together, these findings provide deep understanding of vitiligo pathogenesis and genetic architecture, suggesting that vitiligo represents a tractable model for investigating complex disease genetic architecture and predictive aspects of personalized medicine.

中文翻译：

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白癜风的遗传结构。

白癜风是一种自身免疫性疾病，皮肤黑色素细胞遭到破坏，导致皮肤和毛发变白。对欧洲血统病例的全基因组连锁研究和全基因组关联研究确定了 50 多个白癜风易感位点，定义了黑素细胞导向的自身免疫模型。白癜风遗传力极高，约 2/3 来自常见基因组变异，约 1/3 来自罕见基因组变异；约 20% 的白癜风风险与环境有关。白癜风遗传风险是多基因的，多发性白癜风家族的附加风险比单纯性白癜风家族的附加风险更大。白癜风的发病年龄是双峰的，也涉及主要的遗传因素；MHC 增强子单倍型赋予白癜风 (OR 8.1) 和早期疾病发作的极高风险，增加 HLA-DQB1 mRNA 和 HLA-DQ 蛋白的表达，从而可能促进触发抗原的呈递。白癜风的触发还涉及一个主要的环境因素；白癜风发病年龄的显着延迟，特别是从 1973 年到 2004 年，表明在此期间对白癜风关键环境诱因的暴露或反应减弱。总之，这些发现提供了对白癜风发病机制和遗传结构的深入了解，表明白癜风代表了研究复杂疾病遗传结构和个性化医疗预测方面的易于处理的模型。