Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis
Sliz, Eeva; Huilaja, Laura; Pasanen, Anu; Laisk, Triin; Reimann, Ene; Mägi, Reedik; FinnGen; Estonian Biobank Research Team; Hannula-Jouppi, Katariina; Peltonen, Sirkku; Salmi, Teea; Koulu, Leena; Tasanen, Kaisa; Kettunen, Johannes (2022-03-03)
Sliz, E., Huilaja, L., Pasanen, A., Laisk, T., Reimann, E., Mägi, R., Hannula-Jouppi, K., Peltonen, S., Salmi, T., Koulu, L., Tasanen, K., & Kettunen, J. (2022). Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis. Journal of Allergy and Clinical Immunology, 149(3), 1105-1112.e9. https://doi.org/10.1016/j.jaci.2021.07.043
© 2021 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2022031723881
Tiivistelmä
Abstract
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.
Objectives: 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 (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 < 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.
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