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

作者：E. Sliz, L. Huilaja, A. Pasanen, T. Laisk, E. Reimann, R. Mägi, K. Hannula-Jouppi, S. Peltonen, T. Salmi, L. Koulu, K. Tasanen, J. Kettunen · 发表于：Journal of Allergy and Clinical Immunology · 年份：2021 · DOI：10.1016/j.jaci.2021.07.043 · 被引用次数：88 · 研究领域：Biology、Medicine

BACKGROUND Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high heritability. Previous genome-wide association studies (GWASs) have identified several loci predisposing to AD. These findings explain ∼30% of the variance in AD susceptibility suggesting that further work is required to fully understand the genetic underpinnings. OBJECTIVE To gain additional understanding of the genetic contribution to AD risk by utilizing biobank resources. METHODS We completed a genome-wide meta-analysis of AD in 796,661 individuals (Ncases=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<5x10-8), five of which are novel. In two of the novel loci, we identified missense mutations with deleterious predictions in genes (DSC1, SERPINB7) encoding proteins crucial to epidermal strength and integrity. CONCLUSION These findings elucidate novel genetic pathways involved in AD pathophysiology. The likely involvement of DSC1 and SERPINB7 in AD pathogenesis may offer opportunities for the development of novel treatment strategies for AD in the future.