Location
Moultrie, GA
Start Date
17-4-2026 12:00 PM
End Date
17-4-2026 1:00 PM
Description
Introduction
Keloids are benign fibroproliferative skin tumors arising from dysregulated wound healing and characterized by excessive extracellular matrix deposition. Although nonmalignant, they are frequently associated with pain, pruritus, restricted mobility, and significant cosmetic disfigurement, resulting in substantial impairment in quality of life. The burden of keloid disease is not uniformly distributed across populations, with higher prevalence and severity observed among individuals of African ancestry, suggesting biologic contributors to disease susceptibility. Despite these disparities, mechanisms underlying pathologic scarring remain incompletely defined. Improved characterization of shared and ancestry-specific contributors may advance understanding of dermal fibrosis and support equitable dermatologic care.
Methods
We conducted a genomic analysis using data from the All of Us Research Program. Meta-analysis summary statistics were examined to evaluate rare variant gene burden and genome-wide single-variant associations with keloid disease. Python-based pipelines were used to analyze data stratified by genetic ancestry (African and European). Associated loci were evaluated using the UCSC Genome Browser and Open Targets Genetics and prioritized based on relevance to inflammation, fibroblast activity, extracellular matrix organization, and developmental signaling.
Results
Preliminary analyses identified ancestry-specific and shared loci associated with keloid susceptibility. Several loci mapped to genes involved in immune regulation and extracellular matrix organization, including RIPK2, RNF168, and COL4A3. The implicated genes are located within biological pathways reported to be dysregulated in prior transcriptomic analyses of keloid tissue. However, functional consequences and mechanistic implications of these variants require further validation.
Discussion
These results support a framework in which keloids arise from inflammatory signaling, fibroblast persistence, and extracellular matrix remodeling. Ancestry-specific immune pathways may contribute to disparities, while shared loci highlight standard fibrosis mechanisms. Future research should validate these pathways in human skin models, single-cell studies, and longitudinal wound healing. Targeting inflammation, fibroblast memory, and matrix interactions may offer more durable benefits than collagen-focused approaches. Incorporating ancestry-informed risk markers may enable earlier identification and support precision therapies.
Embargo Period
5-28-2026
Included in
Understanding the Genetic Basis of Keloid Susceptibility Through Multi-Ancestry Genomic Studies
Moultrie, GA
Introduction
Keloids are benign fibroproliferative skin tumors arising from dysregulated wound healing and characterized by excessive extracellular matrix deposition. Although nonmalignant, they are frequently associated with pain, pruritus, restricted mobility, and significant cosmetic disfigurement, resulting in substantial impairment in quality of life. The burden of keloid disease is not uniformly distributed across populations, with higher prevalence and severity observed among individuals of African ancestry, suggesting biologic contributors to disease susceptibility. Despite these disparities, mechanisms underlying pathologic scarring remain incompletely defined. Improved characterization of shared and ancestry-specific contributors may advance understanding of dermal fibrosis and support equitable dermatologic care.
Methods
We conducted a genomic analysis using data from the All of Us Research Program. Meta-analysis summary statistics were examined to evaluate rare variant gene burden and genome-wide single-variant associations with keloid disease. Python-based pipelines were used to analyze data stratified by genetic ancestry (African and European). Associated loci were evaluated using the UCSC Genome Browser and Open Targets Genetics and prioritized based on relevance to inflammation, fibroblast activity, extracellular matrix organization, and developmental signaling.
Results
Preliminary analyses identified ancestry-specific and shared loci associated with keloid susceptibility. Several loci mapped to genes involved in immune regulation and extracellular matrix organization, including RIPK2, RNF168, and COL4A3. The implicated genes are located within biological pathways reported to be dysregulated in prior transcriptomic analyses of keloid tissue. However, functional consequences and mechanistic implications of these variants require further validation.
Discussion
These results support a framework in which keloids arise from inflammatory signaling, fibroblast persistence, and extracellular matrix remodeling. Ancestry-specific immune pathways may contribute to disparities, while shared loci highlight standard fibrosis mechanisms. Future research should validate these pathways in human skin models, single-cell studies, and longitudinal wound healing. Targeting inflammation, fibroblast memory, and matrix interactions may offer more durable benefits than collagen-focused approaches. Incorporating ancestry-informed risk markers may enable earlier identification and support precision therapies.