Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis.
J Allergy Clin Immunol
; 149(3): 1105-1112.e9, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-34454985
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.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 (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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Serpinas
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Dermatitis Atópica
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Desmocolinas
Tipo de estudio:
Prognostic_studies
/
Systematic_reviews
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article