A Genome-Wide Association Study of Hidradenitis Suppurativa from the VA's Million Veteran Program

Introduction: Data from family and twin studies as well as prior genome-wide association meta-analyses suggest that hidradenitis suppurativa (HS) has a hereditary component. This GWAS identifies genetic variants associated with HS.

Individuals with a diagnosis of HS (defined as at least one instance of ICD9 705.83 or ICD10 L73.2) were identified within the Million Veteran Program. Multi-population and population-specific (African, European, and Hispanic ancestries) case-control genome-wide association studies (GWAS) were performed. Lead single-nucleotide polymorphisms were investigated in external resources providing phenome-wide associations (PheWAS), including UK Biobank, HugeAMP, and FinnGen. Demographic and clinical data for cases and controls were taken from the Corporate Data Warehouse and differences between the cases and control group were analyzed.

A total of 4,959 participants with HS were identified among 597,819 MVP participants. The multi-population GWAS identified two significant (p < 5 × 10-8) loci associated with HS, including a novel HS-related variant on chromosome 6 near HLA-DRB1 (lead variant rs679242), and confirmed a previously identified locus on chromosome 17 near SOX9 (rs55811634). The following previously identified loci associated with HS achieved suggestive evidence for association (p < 1 x 10-3): rs17090189 (13q22.1; near KLF5), rs10816701 (9q31.3; near KLF4), rs121908120 (2q35; WNT10A), and rs17103088 (14q24.3; near TMED10).

The analysis of the MVP resource for HS identified a novel signal on chromosome 6 near HLA-DRB1 and identified significant evidence and suggestive evidence for several previously reported signals for HS.