Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Current treatments are limited in their efficacy and tolerance and there is a substantial unmet medical need. Improved understanding of the pathogenic mechanisms of acne is critical for the development of novel therapies that could replace or supplement existing approaches. Here, we perform the largest GWAS meta-analysis to date comprising 20,165 individuals with acne from nine independent cohorts from Australia, Finland, Norway, the Netherlands, the UK and the USA; a four-fold increase in cases on the previous largest acne meta-analysis. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches we identify putative causal genes at several novel acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including ectodermal dysplasia, mandibulofacial dysostosis and pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.

ESDR160 - Genome-wide association meta-analysis of acne reveals 29 novel risk loci and molecular overlap with Mendelian hair and skin disorders and other complex traits

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING