Phenome-wide association of acne susceptibility loci highlights shared and unique biology

The latest genome-wide association studies (GWAS) comprising 20,165 acne cases and 595,231 controls have successfully identified 42 genomic regions associated with increased risk of acne. Yet, it remains unclear the extent to which these individual acne susceptibility loci contribute to other disorders. To begin to identify shared and unique biology underlying acne pathogenesis, we conducted phenome-wide association (PheWAS) of the 42 acne loci across 110 phenotypes with large-scale, well-powered GWAS results that broadly span autoimmune, endocrine, psychiatric, cardiovascular, dermatologic conditions, and cancer, as well as serum and urine biomarkers. Much of the acne loci did not share GWAS signals with any of 110 phenotypes, suggesting that there may be acne-specific biology in these genomic regions. Conversely, we also identified shared genetic effects at several loci with testosterone, sex hormone binding globulin (SHBG), non-albumin protein levels, liver enzymes (AST, AST/ALT ratio), and blood cell phenotypes (MCV, MCH, eosinophil count), some of which recapitulate known acne pathophysiology. Overall, this work highlights shared and unique genetic effects of individual acne GWAS loci via phenome-wide investigation. All GWAS summary statistics used herein and code to reproduce bioinformatic data analyses are publicly available.