Genome-wide association study of atopic and autoimmune comorbidities in alopecia areata

Introduction: Alopecia areata (AA) is a chronic autoimmune-mediated disorder characterized by hair loss from the scalp and/or body. AA patients frequently present with comorbid chronic inflammatory disorders (CIDs), particularly atopic and autoimmune diseases. Genome-wide association (GWA) studies have suggested a genetic link. However, no studies to date have examined genetic factors that are associated with the comorbid development of CIDs directly in individuals affected by AA. Methods: We performed an exploratory GWA study in Central European AA patients stratified by self-reported comorbidity status (110 to 1,302 cases with- and 1,030 controls without comorbid CIDs). Comorbidities were analyzed first as broad atopic and autoimmune categories and subsequently as individual conditions, including asthma, atopic dermatitis, rhinitis, vitiligo, and Hashimoto's thyroiditis. Results: was the most frequently implicated gene, consistent with its previously described role in T- and B-cell biology. Network analyses highlighted cytokine, hormone, and transcription factor signaling pathways as potential mechanisms underlying comorbid CID development in AA. Discussion: Our study provides initial mechanistic insights for comorbid CID development in AA, and a foundation for larger-scale studies.