003 Aging alteration of skin T cells is different from that of blood T cells

Abstract

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 twofold 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 of 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). Controls were identified as having no record of any immune mediated disease as defined by 28,419 ICD codes. Principal component analysis was used to estimate ancestry from a set of 40,156 SNPs. Our final cohort consisted of 455 HS cases and 1,178 controls with comparable multi-ethnic ancestry (l¼1.06). Genotype data for 40 million variants was tested for association, adjusting for five principle components and run using PLINK (v1.9). Six loci approached the threshold for genome-wide significance (p<5x10-8), with p-values that ranged between 2.0x10-7 and 9.9x10-7 , and effect estimates (2.36>OR>1.43) that suggest a moderate expansion in sample size will allow us to exceed genome-wide significance. There was no evidence for HLA association supporting classification of HS as inflammatory rather than autoimmune. Our group is constructing multi-ethnic replication cohorts that will allow us to expand this study in the near future.