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

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 x 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.

Automated summary

This study aimed to gain a better understanding of the genetic contribution to atopic dermatitis (AD) risk by utilizing biobank resources. Through a genome-wide meta-analysis, the researchers identified 30 loci associated with AD, including 5 novel loci. Two of the novel loci were found to have missense mutations in genes crucial to the integrity and strength of the epidermis. These findings provide insights into novel genetic pathways involved in AD pathophysiology and potential opportunities for future treatment strategies.