Multi-Ancestry Genome-Wide Association Meta-Analysis Identifies Novel Loci in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to AD genetic association studies are poised to boost power to detect genetic signal and identify ancestry-specific loci contributing to AD risk. Here, we present a multi-ancestry GWAS meta-analysis of twelve AD cohorts from five ancestral populations totaling 56,146 cases and 602,280 controls. We report 101 genomic loci associated with AD, including 15 loci that have not been previously associated with AD or eczema. Fine-mapping, QTL colocalization, and cell-type enrichment analyses identified genes and cell types implicated in AD pathophysiology. Functional analyses in keratinocytes provide evidence for genes that could play a role in AD through epidermal barrier function. Our study provides new insights into the etiology of AD by harnessing multiple genetic and functional approaches to unveil the mechanisms by which AD-associated variants impact genes and cell types. Disclosure StatementBRG, MO, CH, KMS are employees of AbbVie. FT was an employee of AbbVie at the time of the study. JEG (University of Michigan) has received research support from AbbVie, Janssen, Almirall, Prometheus Biosciences/Merck, BMS/Celgene, Boehringer Ingelheim, Galderma, Eli Lilly, and advisor to Sanofi, Eli Lilly, Galderma, BMS, Boehringer Ingelheim. MKS, RU, MTP, QL, RW, JMK, LCT are employees of University of Michigan and have no funding to disclose. MEM, AHS, FDM, DW, JTG, HH are employees of the Childrens Hospital of Philadelphia and no funding to disclose. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.