Urticaria is a common group of diseases characterised by different morphologies of dermal oedema, namely wheals and angioedema. It may be classified into acute and chronic forms and, although mast cell degranulation is a pathologic feature in all urticaria types, its aetiopathogenesis is otherwise incompletely understood. Twin and family studies suggest that urticaria is a heritable trait, while its population frequency and limited effects on reproductive fitness imply a polygenic architecture. To explore the genetic aetiology of all types of urticaria in European populations, we performed a genome-wide association study (GWAS) on UK Biobank participants of white British ancestry. Urticaria cases were identified using electronic healthcare record diagnoses from hospital (ICD10) and primary care (read codes, v2 and CTv3) encounters. We combined summary statistics from this and other European GWAS studies (FinnGen, HUNT) in a fixed-effects meta-analysis, analysing 14,306 cases and 650,664 controls in total. To explore potential causal genes, eQTL look-up and co-localisation were performed. Our meta-analysis identified genome-wide significant associations (p < 5 x 10-8) at six distinct loci, including the human leukocyte antigen region on chromosome 6. Co-localisation indicative of shared causal variants was observed between urticaria susceptibility and GCSAML expression at 1q44 (posterior probability (PP)=88.6%) and with FCER1A expression at 1q23.2 (PP=90.6%). GCSAML plays a predicted role in germinal centre signalling, while FCER1A mediates IgE-dependent mast cell activation. Our study indicates that common genetic variation at six loci influences urticaria susceptibility and through GCSAML and FCER1A, implicates mast cell and other immune mechanisms in urticaria pathogenesis.

LB062 - Genome-wide meta-analysis in European populations identifies novel susceptibility loci in urticaria

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.