Integration of genome-wide transcriptional and genetic profiles provides insights into disease development and clinical heterogeneity in Alopecia areata

Alopecia areata (AA), a non-scarring inflammatory hair loss disorder, is a complex disease determined by genetic and environmental factors that remain largely unknown. Re-analysis of genome-wide microarray data in 9 patient blood and 10 skin samples revealed transcriptional “hot spots” at chromosomes 1q21–q32, 11q12–q14, and 16p13–p13.3 (blood) and 6p21.3, 12q12–q13, and 17q12–q24 (skin) harboring high densities of dysregulated genes. We then integrated AA associated gene expression profiles with previous genome-wide genetic analyses to identify a subset of 112 dysregulated genes that map to putative susceptibility loci. Finally, we analyzed AA patients stratified by defined clinical characteristics, including a history of atopy, autoimmune disease, and nail disease, thus deconstructing the clinical heterogeneity observed among AA patients. Integrated chromosomal and transcriptional profiling identified several dysregulated chromosomal regions and genes representing an enriched set of biomarkers relevant to AA pathogenesis and clinical heterogeneity.

► We examined genome-wide gene expression of peripheral blood and skin in AA patients. ► Transcriptional “hot spots” found at chromosomes 1q, 6p, 11q, 12q, 16p, and 17q. ► We identify 112 AA DEGs that map to recently identified AA susceptibility loci. ► Chromosomal loci associated with AA disease DEGs overlap atopy susceptibility loci. ► Expression profiling distinguishes AA patients based on their history of atopy.