Vitiligo is a common autoimmune disease characterized by patches of depigmented skin and overlying hair due to destruction of melanocytes in the involved regions. We investigated the relationship between vitiligo risk and vitiligo age of onset (AOO) using a vitiligo polygenic risk score that incorporated the most significant SNPs from genome-wide association studies. We find that vitiligo genetic risk and AOO are strongly inversely correlated; subjects with higher common-variant polygenic risk tend to develop vitiligo at an earlier age. Nevertheless, the correlation is not simple. In individuals who carry a single high-risk major histocompatibility complex class II haplotype, the effect of additional polygenic risk on vitiligo AOO is reduced. Particularly among those with early-AOO vitiligo (onset ≤12 years of age), genetic risk can reflect contributions from high common-variant burden but also rare variants of high effect and sometimes both. While the heritability of vitiligo is relatively high, and we here show that genetic risk factors predict vitiligo AOO, vitiligo is never congenital, and thus environmental triggers also play an important role in disease onset.

中文翻译：

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多基因风险负担与自身免疫性白癜风发病年龄呈负相关关系


白癜风是一种常见的自身免疫性疾病，其特征是由于受累区域的黑色素细胞破坏而出现脱色皮肤斑块和覆盖的头发。我们使用白癜风多基因风险评分调查了白癜风风险与白癜风发病年龄 （AOO） 之间的关系，该评分纳入了来自全基因组关联研究的最显着 SNP。我们发现白癜风遗传风险和 AOO 呈强负相关;具有较高常见变异多基因风险的受试者往往在较早的年龄患上白癜风。然而，相关性并不简单。在携带单一高危主要组织相容性复合体 II 类单倍型的个体中，额外多基因风险对白癜风 AOO 的影响降低。特别是在早期 AOO 白癜风 （发病≤12 岁） 患者中，遗传风险可以反映高常见变异负担的贡献，但也反映了高效果的罕见变异，有时两者兼而有之。虽然白癜风的遗传性相对较高，并且我们在这里表明遗传风险因素预测白癜风 AOO，但白癜风从来都不是先天性的，因此环境触发因素在疾病发作中也起着重要作用。