# Determining the Genetic Basis of Hidradenitis Suppurativa

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $459,879

## Abstract

PROJECT SUMMARY/ABSTRACT
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has a devastating effect on quality of
life. HS affects up to 1.2% of people and disproportionately affects women and Black people. The age of onset
is typically in adolescence/young adulthood and symptoms persist for decades. More than half of patients have
affected family members, consistent with a strong genetic contribution to HS. Variants implicated in familial cases
of HS have been reported in four genes, three of which encode subunits of the γ-secretase complex, but these
likely affect less than 5% of patients with HS, raising the question: what other variants may be at play?
In our recent genome-wide association study (GWAS) of 760 patients and meta-analysis with additional cohorts,
we identified significant risk loci near SOX9 and KLF5, which play important roles in follicular and epidermal
maintenance, wound healing, and inflammation. We hypothesize that larger sample sizes will identify additional
significant risk loci that will substantially improve our understanding of disease pathogenesis and identify
potential treatment targets. We further hypothesize that dysregulated SOX9 and KLF5 expression will be found
in the hair follicles, epidermis, and cutaneous tunnels in skin from HS patients.
In this study, we propose to build upon our recent GWAS to examine the genetic basis of HS in an expanded
cohort of 2,000 diverse patients with HS at the University of North Carolina at Chapel Hill. We continue to recruit
participants from one of the highest volume HS subspecialty clinics in the country. Approximately 50% of our
cohort is composed of Black patients, and we will examine potential differences in the genetic architecture based
on ancestry, sex, and phenotypic diversity. We also will perform GWAS in the All of Us cohort and meta-analyze
GWAS results with the FinnGen, UK Biobank, and BioVU biobanks, and other cohorts as described in the
research plan. This meta-analysis will include more than 12,000 total subjects. Identifying genetic variants that
show evidence for association with HS disease status will provide candidate genes for further validation and
biological study to develop new treatments and possibly prevent disease. At the recently discovered GWAS loci
near SOX9 and KLF5, we will analyze gene expression patterns in HS-affected tissue using RNA-seq and
immunohistochemistry. To identify candidate genes for new loci, we will analyze transcriptome data to identify
variants associated with both HS and gene expression and integrate with existing chromatin data. To identify HS
risk variants that affect gene expression, we will evaluate skin cell transcriptome and epigenome data and
perform reporter assays in keratinocytes. By identifying dysregulated gene expression patterns in the epidermis,
hair follicles, and cutaneous tunnels of HS-affected tissue, we will learn how risk variants contribute to follicular
disruption, inflammatory re...

## Key facts

- **NIH application ID:** 10981410
- **Project number:** 1R01AR083790-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Yun Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $459,879
- **Award type:** 1
- **Project period:** 2024-08-22 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981410

## Citation

> US National Institutes of Health, RePORTER application 10981410, Determining the Genetic Basis of Hidradenitis Suppurativa (1R01AR083790-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10981410. Licensed CC0.

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