斑秃
外显子组测序
毛囊
外显子组
全基因组关联研究
男性型秃发
毛发病
医学
泛秃
脱发
皮肤病科
生物
遗传学
基因
基因型
突变
头皮
内分泌学
单核苷酸多态性
作者
S. Erjavec,Sahar Gelfman,A.R. Abdelaziz,Eunice Lee,Isha Monga,Anna Alkelai,Iuliana Ionita‐Laza,Lynn Petukhova,Angela M. Christiano
标识
DOI:10.1038/s41467-022-28343-3
摘要
Alopecia areata is a complex genetic disease that results in hair loss due to the autoimmune-mediated attack of the hair follicle. We previously defined a role for both rare and common variants in our earlier GWAS and linkage studies. Here, we identify rare variants contributing to Alopecia Areata using a whole exome sequencing and gene-level burden analyses approach on 849 Alopecia Areata patients compared to 15,640 controls. KRT82 is identified as an Alopecia Areata risk gene with rare damaging variants in 51 heterozygous Alopecia Areata individuals (6.01%), achieving genome-wide significance (p = 2.18E-07). KRT82 encodes a hair-specific type II keratin that is exclusively expressed in the hair shaft cuticle during anagen phase, and its expression is decreased in Alopecia Areata patient skin and hair follicles. Finally, we find that cases with an identified damaging KRT82 variant and reduced KRT82 expression have elevated perifollicular CD8 infiltrates. In this work, we utilize whole exome sequencing to successfully identify a significant Alopecia Areata disease-relevant gene, KRT82, and reveal a proposed mechanism for rare variant predisposition leading to disrupted hair shaft integrity.
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