Integrative Analysis of Rare Copy Number Variants and Gene Expression Data in Alopecia Areata Implicates an Etiological Role for Autophagy

In the 2019 study, researchers analyzed genetic data from 758 alopecia areata (AA) patients and 17,769 controls to explore the genetic basis of AA. They found an excess of rare, large, gene-disrupting copy number variants (CNVs) in AA patients compared to controls. By integrating CNV data with gene expression profiles, they identified 35 genes affected by CNVs that were also altered in AA gene expression signatures. Notably, genes such as ATG4B, involved in autophagy, and SMARCA2, involved in chromatin remodeling, were implicated in multiple AA patients, suggesting their role in AA pathogenesis. Immunofluorescence analysis supported the involvement of these genes in hair follicle biology. The study indicates that rare CNVs may contribute to AA's genetic architecture and highlights autophagy as a potential pathway in the disease's etiology.