Whole Exome Sequencing in Alopecia Areata Identifies Rare Variants in KRT82

February 2022 in “ Nature communications ”

S. Erjavec, Sahar Gelfman, A.R. Abdelaziz, Eunice Lee, Isha Monga, Anna Alkelai, Iuliana Ionita‐Laza, Lynn Petukhova, Angela M. Christiano

Alopecia Areata KRT82 hair-specific keratin hair shaft cuticle CD8 immune cell infiltrates hair follicles hair shaft integrity hair loss immune response

Studysummary This study identified KRT82 as a significant Alopecia Areata risk gene, finding that rare damaging variants are linked to elevated immune cell infiltration around hair follicles in affected individuals. Our plain-language summary of this paper — not a Tressless recommendation.

Using whole exome sequencing and gene-level burden analyses on 849 patients with Alopecia Areata and 15,640 controls, this study identified rare damaging variants in the KRT82 gene as a significant risk factor for the disease. KRT82, which is a hair-specific keratin expressed in the hair shaft cuticle, was found to have rare variants in 51 heterozygous individuals (6.01%) with Alopecia Areata, reaching genome-wide significance with a p-value of 2.18E-07. The study also noted that Alopecia Areata patients with these KRT82 variants showed decreased expression of the gene and had increased CD8 immune cell infiltrates around hair follicles, suggesting a mechanism where these variants may contribute to hair loss by affecting hair shaft integrity and triggering an immune response.

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