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European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N=1,086,394, replication N=3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis and 15 additional loci in the multi-ancestry analysis (6 novel). All 81 variants replicated in a separate European analysis. Eleven variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African). While four variants appeared to be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL signals in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.