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 ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.
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Gene Expression Omnibus
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This publication is the work of the authors, and L.P. will serve as guarantor for the contents of this paper. This research was specifically funded by an MRC Population Health Scientist Fellowship awarded to L.P. (MR/J012165/1). D.M.E. is supported by an Australian Research Council Future Fellowship (FT130101709) and a Medical Research Council program grant (MC_UU_12013/4). Individual study acknowledgment and funding statements can be found in the Supplementary Note.
C.T., D.A.H. and J.Y.T. are employees of and own stock or stock options in 23andMe, Inc. K.M.G. has received reimbursement for speaking at conferences sponsored by companies selling nutritional and pharmaceutical products. He is part of an academic consortium that has received funding from Abbott Nutrition, Nestec and Danone. The University of Groningen has received money for D.S.P. in the context of an unrestricted educational grant for research from AstraZeneca. Fees for consultancies were given to the University of Groningen by AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Takeda and TEVA. A.C. reports personal fees from AstraZeneca, personal fees from Novartis and personal fees from ThermoFisher given outside the context of the current manuscript. A.S. reports personal fees from GlaxoSmithKline and personal fees from ThermoFisher given outside the context of the current manuscript.
A full list of members and affiliations is provided in the Supplementary Note.
Supplementary Figures 1–8, Supplementary Tables 1–4, 11–16, 22 and 23, and Supplementary Note. (PDF 20319 kb)
Look-ups of known SNPs for various autoimmune diseases. (XLSX 48 kb)
Functional investigations of credible SNPs. (XLSX 190 kb)
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Paternoster, L., Standl, M., Waage, J. et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 47, 1449–1456 (2015) doi:10.1038/ng.3424
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