Location
Moultrie, GA
Start Date
17-4-2026 12:00 PM
End Date
17-4-2026 1:00 PM
Description
Introduction
Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the folliculopilosebaceous unit affecting intertriginous areas including the axillae, groin, buttocks, and inframammary regions. It presents with recurrent painful nodules, abscesses, sinus tracts, and scarring, leading to substantial physical and psychosocial burden. Up to 40% of patients report severe quality-of-life impairment, with strong associations to depression and work disability. HS disproportionately affects individuals of African ancestry and demonstrates disparities in disease burden. Despite its clinical impact, the genetic architecture of HS remains incompletely defined, particularly across diverse populations. Although rare familial cases implicate γ-secretase pathway mutations, broader genetic contributors to sporadic HS are not well characterized.
Methods
We conducted a genomic analysis using data from the All of Us Research Program. Meta- analysis summary statistics were evaluated to assess rare gene burden and genome-wide single-variant associations with HS. Python-based analytic pipelines were implemented in Jupyter Notebooks to analyze All of Us data stratified by genetic ancestry, focusing on individuals of African (AFR) and European (EUR) ancestry. Significant loci were examined using the UCSC Genome Browser to assess nearby genes and biological plausibility. Findings were interpreted within established models of HS pathophysiology, including follicular occlusion, epithelial dysregulation, and chronic innate immune activation.
Results
Preliminary analyses identified both shared and ancestry-specific loci associated with HS. Several loci mapped to non-coding regions, suggesting regulatory variation contributes to disease susceptibility. Among protein-coding candidates, variants were identified near FHIT and CCDC102A. FHIT encodes a tumor suppressor involved in DNA damage response, apoptosis, and maintenance of epithelial integrity. Reduced FHIT expression has been linked to impaired epithelial repair and increased inflammatory signaling. Given that HS lesions demonstrate chronic epithelial injury and abnormal wound healing, altered FHIT-mediated stress responses may contribute to follicular instability and persistent inflammation. CCDC102A encodes a centrosome-associated protein required for centrosome cohesion and regulation of cell cycle progression. Centrosome dysfunction can disrupt epithelial proliferation and differentiation. Because early HS pathology involves follicular hyperplasia and keratinocyte dysregulation, variation affecting CCDC102A-related cell cycle control may promote abnormal follicular architecture and occlusion.
Discussion
These findings suggest HS susceptibility may be influenced by ancestry-specific and shared genetic variation affecting epithelial stress responses and proliferative control. The predominance of non-coding loci further supports a regulatory contribution to disease risk. Future studies should determine how these variants influence gene expression and protein activity in skin. Comparing lesional and non-lesional HS tissue may clarify whether FHIT, CCDC102A, or nearby regulatory elements are altered in active disease. Functional studies of keratinocyte proliferation and inflammatory signaling may further define their role in follicular occlusion. Understanding epithelial stress-response and cell-cycle pathways may expand therapeutic targets beyond cytokine blockade. Therapies aimed at improving epithelial repair or regulating keratinocyte growth could complement existing TNF-α and IL-17 inhibitors. Incorporating ancestrally diverse genomic data advances equitable understanding of HS biology and supports development of mechanism-driven treatment approaches.
Embargo Period
5-28-2026
Included in
Many Genomes, One Disease: Genetic Risk of Hidradenitis Suppurativa Across Ancestries
Moultrie, GA
Introduction
Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the folliculopilosebaceous unit affecting intertriginous areas including the axillae, groin, buttocks, and inframammary regions. It presents with recurrent painful nodules, abscesses, sinus tracts, and scarring, leading to substantial physical and psychosocial burden. Up to 40% of patients report severe quality-of-life impairment, with strong associations to depression and work disability. HS disproportionately affects individuals of African ancestry and demonstrates disparities in disease burden. Despite its clinical impact, the genetic architecture of HS remains incompletely defined, particularly across diverse populations. Although rare familial cases implicate γ-secretase pathway mutations, broader genetic contributors to sporadic HS are not well characterized.
Methods
We conducted a genomic analysis using data from the All of Us Research Program. Meta- analysis summary statistics were evaluated to assess rare gene burden and genome-wide single-variant associations with HS. Python-based analytic pipelines were implemented in Jupyter Notebooks to analyze All of Us data stratified by genetic ancestry, focusing on individuals of African (AFR) and European (EUR) ancestry. Significant loci were examined using the UCSC Genome Browser to assess nearby genes and biological plausibility. Findings were interpreted within established models of HS pathophysiology, including follicular occlusion, epithelial dysregulation, and chronic innate immune activation.
Results
Preliminary analyses identified both shared and ancestry-specific loci associated with HS. Several loci mapped to non-coding regions, suggesting regulatory variation contributes to disease susceptibility. Among protein-coding candidates, variants were identified near FHIT and CCDC102A. FHIT encodes a tumor suppressor involved in DNA damage response, apoptosis, and maintenance of epithelial integrity. Reduced FHIT expression has been linked to impaired epithelial repair and increased inflammatory signaling. Given that HS lesions demonstrate chronic epithelial injury and abnormal wound healing, altered FHIT-mediated stress responses may contribute to follicular instability and persistent inflammation. CCDC102A encodes a centrosome-associated protein required for centrosome cohesion and regulation of cell cycle progression. Centrosome dysfunction can disrupt epithelial proliferation and differentiation. Because early HS pathology involves follicular hyperplasia and keratinocyte dysregulation, variation affecting CCDC102A-related cell cycle control may promote abnormal follicular architecture and occlusion.
Discussion
These findings suggest HS susceptibility may be influenced by ancestry-specific and shared genetic variation affecting epithelial stress responses and proliferative control. The predominance of non-coding loci further supports a regulatory contribution to disease risk. Future studies should determine how these variants influence gene expression and protein activity in skin. Comparing lesional and non-lesional HS tissue may clarify whether FHIT, CCDC102A, or nearby regulatory elements are altered in active disease. Functional studies of keratinocyte proliferation and inflammatory signaling may further define their role in follicular occlusion. Understanding epithelial stress-response and cell-cycle pathways may expand therapeutic targets beyond cytokine blockade. Therapies aimed at improving epithelial repair or regulating keratinocyte growth could complement existing TNF-α and IL-17 inhibitors. Incorporating ancestrally diverse genomic data advances equitable understanding of HS biology and supports development of mechanism-driven treatment approaches.