| Title: | Genomic loci and molecular genetic mechanisms for hidradenitis suppurativa |
| Journal: | British Journal of Dermatology |
| Published: | 12 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40650879/ |
| DOI: | https://doi.org/10.1093/bjd/ljaf277 |
| URL: | https://academic.oup.com/bjd/advance-article-pdf/doi/10.1093/bjd/ljaf277/63735275/ljaf277.pdf |
Publication 16982
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Abstract
BACKGROUND: Hidradenitis suppurativa (HS) is a common, chronic and debilitating inflammatory disease that most commonly affects intertriginous skin. Despite its high heritability, the genetic underpinnings of HS remain poorly understood.</p>
OBJECTIVES: To identify genetic signals associated with HS, determine genetic relationships with other diseases and investigate potential molecular genetic mechanisms.</p>
METHODS: We performed a genome-wide association meta-analysis of six studies, totalling 4540 patients with HS and > 1 million control participants, and identified genetic correlations with other common diseases. We integrated the HS data with expression quantitative trait loci from 10 trait-relevant tissues, epigenomic and transcriptomic data from human scalp, differential expression data from HS lesions vs. adjacent skin and mesenchymal Hi-C chromatin looping data. To identify functional noncoding variants, we performed transcriptional reporter assays for signals near KLF5 and SOX9.</p>
RESULTS: We identified 11 significant HS signals across 7 loci: 4 corresponded to previously reported associations, 4 represented novel signals within known loci and 3 were signals in newly implicated loci. We identified significant genetic correlations between HS and other inflammatory conditions, particularly inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes mellitus and asthma. We prioritized candidate genes for the 11 signals. The risk allele at KLF5 exhibited 10-fold greater transcriptional activity than the nonrisk allele, while risk alleles at SOX9 showed significantly reduced transcriptional activity.</p>
CONCLUSIONS: Our results provide insights into potential genetic mechanisms underlying HS and suggest potential therapeutic targets for this challenging condition.</p>
8 Keywords
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Hidradenitis Suppurativa
- Humans
- Kruppel-Like Transcription Factors
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
- SOX9 Transcription Factor
28 Authors
- K Alaine Broadaway
- Quan Sun
- Sharon N Edmiston
- Kevin W Currin
- Swarooparani Vadlamudi
- Tyne W Miller-Fleming
- Yue Shi
- Kristen Fajgenbaum
- Maria Melendez-Gonzalez
- Helen Bui
- Franklin R Blum
- Linnea Westerkam
- Rayad Shams
- Teja Mallela
- Brandt Levitt
- Lan Lin
- Honglin Hao
- Aylin Memili
- Peter Straub
- Wei Zhou
- Kathleen Mullan Harris
- Alicia Martin
- Nancy J Cox
- Zhi Liu
- Nancy E Thomas
- Yun Li
- Karen L Mohlke
- Christopher J Sayed
1 Application
| Application ID | Title |
|---|---|
| 25953 | Transcriptome-wide Association Study of Cardiometabolic Traits in the UK Biobank Cohort |
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