Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis

Abstract

<p>Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high heritability. Previous genome-wide association studies have identified several loci predisposing to AD. These findings explain approximately 30% of the variance in AD susceptibility, suggesting that further work is required to fully understand the genetic underpinnings. Objective: We sought to gain additional understanding of the genetic contribution to AD risk by using biobank resources. Methods: We completed a genome-wide meta-analysis of AD in 796,661 individuals (N_cases = 22,474) from the FinnGen study, the Estonian Biobank, and the UK Biobank. We further performed downstream in silico analyses to characterize the risk variants at the novel loci. Results: We report 30 loci associating with AD (P < 5 × 10⁻⁸), 5 of which are novel. In 2 of the novel loci, we identified missense mutations with deleterious predictions in desmocollin 1 and serpin family B member 7, genes encoding proteins crucial to epidermal strength and integrity. Conclusions: These findings elucidate novel genetic pathways involved in AD pathophysiology. The likely involvement of desmocollin 1 and serpin family B member 7 in AD pathogenesis may offer opportunities for the development of novel treatment strategies for AD in the future.</p>