Utilizing Functional Genomics Approaches to Characterize Risk Genes in Alopecia Areata

This doctoral thesis explored the genetic underpinnings of Alopecia Areata (AA), a complex autoimmune disease causing hair loss, by employing targeted genomic sequencing and whole exome sequencing (WES). The study identified potentially causal variants in genes affecting hair follicles, particularly focusing on the Syntaxin 17 (STX17) gene and Keratin 82 (KRT82). In 849 AA patients, 35 non-coding variants in the STX17 region were linked to reduced gene expression and increased immunogenicity, while rare damaging mutations in KRT82 were found in 51 patients, suggesting a weakened hair follicle cuticle predisposes to immune attack. These findings highlighted novel genetic contributions to AA, emphasizing the role of hair follicle perturbations in disease risk.