A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in androgenetic alopecia

Abstract

We studied genome-wide gene expression from bald and haired scalp of individuals to evaluate pathogenic mechanisms underlying the development and progression of androgenetic alopecia (AGA). Unbiased analyses revealed a "bald pathology" based signature. Ontology enrichment analyses of the differentially expressed genes (DEGs) underscored apoptosis, cell proliferation, perturbed neurological pathways, and WNT signaling as central drivers of the hair loss process. Interactome analysis uncovered several known and novel key transcriptional regulators potentially affecting disease pathogenesis both within and "hidden" from the dataset. One DEG mapped within one of the fourteen identified transcriptionally active "hot spots" across the genome and coincided with a previous AGA-associated gene. The remaining DEGs within the "hot spots" offer an additional set of potential disease linked loci that may help to guide future studies aimed at identifying disease risk genes. Finally, we used in silico analyses to identify five molecular targets for exploration in future AGA therapies.