Genevieve H L Roberts, Pamela R Fain, Stephanie A Santorico, Richard A Spritz
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引用次数: 0
摘要
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遭到破坏而导致皮肤和毛发上出现色素脱失斑。我们使用白癜风多基因风险评分,结合全基因组关联研究中最重要的 SNPs,研究了白癜风风险与白癜风发病年龄(AOO)之间的关系。我们发现,白癜风遗传风险与发病年龄呈强烈的反比关系;共变异多基因风险较高的受试者往往会在较早的年龄患上白癜风。然而,这种相关性并不简单。在携带单一高风险主要组织相容性复合体 II 类单倍型的个体中,额外的多基因风险对白癜风 AOO 的影响会减弱。特别是在早期AOO型白癜风患者中(发病年龄小于12岁),遗传风险可能反映了高共变异负担的贡献,也可能反映了高效应的罕见变异,有时两者兼而有之。虽然白癜风的遗传率相对较高,而且我们在此表明,遗传风险因素可预测白癜风AOO,但白癜风从来都不是先天性的,因此环境诱因在疾病发病中也发挥着重要作用。
Inverse relationship between polygenic risk burden and age of onset of autoimmune vitiligo.
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.
期刊介绍:
The American Journal of Human Genetics (AJHG) is a monthly journal published by Cell Press, chosen by The American Society of Human Genetics (ASHG) as its premier publication starting from January 2008. AJHG represents Cell Press's first society-owned journal, and both ASHG and Cell Press anticipate significant synergies between AJHG content and that of other Cell Press titles.