Acne inversa, also known as hidradenitis suppurativa (HS), is a neglected, prevalent, chronic, stigmatizing, and debilitating inflammatory skin disease. HS patients suffer from deep, painful, recurrent abscesses that drain malodorous fluid and lead to disfiguring scars that can limit mobility of the arms and legs.  People with African ancestry have a more than two-fold increased risk of HS.  A lack of effective therapies and limited knowledge about HS pathogenesis contribute to unmet needs. Unlike other common inflammatory skin diseases, there never has been a genome-wide association study (GWAS) conducted for HS. We performed a GWAS for HS using data obtained from the electronic MEdical Records & GEnomics (eMERGE) network of electronic health record linked biorepositories.  Cases were identified by the presence of at least one diagnosis code for HS (ICD-9 705.83; ICD-10 L73.2). Controls were identified no HS diagnostic code. Principal component analysis was used to estimate ancestry from a set of 40,156 SNPs. Our final cohort consisted of 600 HS cases and 82,611 controls with comparable multi-ethnic ancestry (λ=1.005). Genotype data for 40 million variants was tested for association, adjusting for five principle components and run using PLINK (v1.9).  No locus exceeded our threshold for statistical significance. There was no evidence for HLA association supporting classification of HS as inflammatory rather than autoimmune.  Several loci approached the significance threshold, suggesting that a moderate expansion in cohort size will provide us adequate power to detect associations.  Interestingly, the lead SNP at one of the most significant  loci is an eQTL for NFAT5, a mediator of NOTCH signaling whose expression is downregulated in HS lesional skin relative to patient-matched nonlesional skin.  The risk allele influences expression in tissue specific manner.  This finding awaits replication. Our group is constructing multi-ethnic replication cohorts that will allow us to expand this study in the near future.

Genome-wide association study of acne inversa in a multi-ethnic cohort