Alopecia Areata study with WXS data on dbGaP (849 participants)

phs002632 — Whole Exome Sequencing in Alopecia Areata Identifies Rare Mutations in    KRT82

<p>Alopecia areata (AA) is an autoimmune disorder, in which the body's own immune cells attack hair follicels resulting in hair loss. It is a complex genetic disease with 14 associated loci previously identified in our genome-wide association study (GWAS). In the study, we performed the whole-exome sequencing (WES) on 849 AA patients with the aim to identify the novel rare variants in genes contributing to AA susceptibility. We performed gene-collapsing analyses and identified keratin 82 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=KRT82">KRT82 Gene ID: 3888</a>) as the highest associated AA gene in the three rare damaging collapsing models with p&#x3C;6.7E-07 in one of the models. The KRT82 gene is a hair-specific type II keratin expressed in the hair shaft cuticle during the anagen phase of the hair cycle. We reported the lower expression of KRT82 in AA hair follicles, compared to controls, and the KRT82 expression is absent from the bulb region, the site of AA immune attack. This study emphasizes the significance of using WES and gene collapsing analyses to identify rare variation in a functionally relevant risk gene using a moderate sample size.  </p>