{Reference Type}: Journal Article
{Title}: Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis.
{Author}: 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;
{Journal}: J Allergy Clin Immunol
{Volume}: 0
{Issue}: 0
{Year}: Aug 2021 27
{Factor}: 14.29
{DOI}: 10.1016/j.jaci.2021.07.043
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>We sought to gain additional understanding of the genetic contribution to AD risk by using biobank resources.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.