Genetic Variants Associated With Hidradenitis Suppurativa

Area of Science:

• Genetics
• Dermatology
• Inflammatory Diseases

Background:

• Hidradenitis suppurativa (HS) is a common, severe, and highly heritable chronic inflammatory skin condition.
• Current understanding of HS genetics is limited, with few genome-wide association studies (GWASs) identifying significant risk loci.

Purpose of the Study:

• To identify genetic variants associated with HS.
• To elucidate the underlying genes and genetic mechanisms contributing to HS development.

Main Methods:

• A genetic association study involving 753 HS patients (720 in analysis) and controls from the Add Health study.
• Meta-analysis with UK Biobank and FinnGen biobanks, followed by replication in the BioVU biobank.
• Genome-wide association study (GWAS) and variant analysis with a significance threshold of P < 1 × 10-8.

Main Results:

• Two HS-associated loci were identified and replicated in a meta-analysis of four studies.
• Lead variants rs10512572 (near SOX9) and rs17090189 (near KLF5) showed significant association (P=2.3×10-11 and P=2.1×10-8, respectively).
• Associated variants are located within enhancer regulatory elements in skin tissue.

Conclusions:

• Common variants near SOX9 and KLF5 are associated with HS risk.
• These genes may play a role in HS pathogenesis, influencing clinical features like cysts and inflammatory tunnels.
• Findings may guide future predictions of disease progression and development of novel HS treatments.