Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Abstract

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified 10 novel risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with novel secondary signals at 4 of these). Notably, the new loci include candidate genes with roles in regulation of innate host defenses and T-cell function, underscoring the important contribution of (auto-)immune mechanisms to atopic dermatitis pathogenesis.

LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis

“…As expected, the estimated genetic correlation (rG) between AD and asthma was strongly significant and positive. We also note that the rG between AD and Crohn's disease was moderate, significant and positive, perhaps reflecting substantial overlap between currently known loci for both conditions (Paternoster et al 2015). rG did not differ significantly from zero for the other traits, although the point estimates for several were moderate indi-cating that follow up when larger samples become available may be justified.…”

Biomarkers for atopic dermatitis

“…61 In addition, a polymorphism in the IL-7R gene that lead to enhanced IL-7 bioactivity, was genetically associated to susceptibility to AD. [62][63][64] The same IL-7R polymorphism is associated with higher risk of type I diabetes, 65 rheumatoid arthritis, 66 sarcoidosis, 67 multiple sclerosis 68 and asthma. 69 These findings make the IL-7 axis interesting as a therapeutic target in AD, but also highlight the link between systemic diseases and AD.…”

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

“…Realizing that large and inclusive international collaborative efforts are essential in providing new biological leads in complex disease pathogenesis [15][16][17][18][19][20] , we report here a world-wide collaborative XFS study aimed at further understanding the genetic basis of the disorder. Firstly, due to the allele reversals seen at LOXL1 common polymorphisms led by rs3825942 G>A (p.153Gly>Asp) and to a lesser extent, rs1048661 T>G (p.141Leu>Arg) 12,[21][22][23][24][25][26][27][28] (Supplementary Figure 1), we aimed to refine the LOXL1 genetic landscape by performing deep sequencing of the entire gene in 5,570 XFS and XFG cases and 6,279 controls from 9 countries (Supplementary Table 1).…”