Genomic Loci and Molecular Genetic Mechanisms For Hidradenitis Suppurativa.

Details

• Alternative Title:
  The British Journal of Dermatology, 2025, v. 193, no. 5: Genomic Loci and Molecular Genetic Mechanisms For Hidradenitis Suppurativa.
• Journal Article:
  The British Journal of Dermatology
• Personal Author:
  Broadaway, K. Alaine ; Sun, Quan ; Edmiston, Sharon N ; Currin, Kevin W ; Vadlamudi, Swarooparani ; Miller-Fleming, Tyne W ; Shi, Yue ; Fajgenbaum, Kristen ; Melendez-Gonzalez, Maria ; Bui, Helen ; Blum, Franklin R ; Westerkam, Linnea ; Shams, Rayad ; Mallela, Teja ; Levitt, Brandt ; Lin, Lan ; Hao, Honglin ; Memili, Aylin ; Straub, Peter ; Zhou, Wei ; Harris, Kathleen Mullan ; Martin, Alicia ; Cox, Nancy J ; Liu, Zhi ; Thomas, Nancy E ; Li, Yun ; Mohlke, Karen L ; Sayed, Christopher J
• Description:
  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.
  
  To identify genetic signals associated with HS, determine genetic relationships with other diseases and investigate potential molecular genetic mechanisms.
  
  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.
  
  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.
  
  Our results provide insights into potential genetic mechanisms underlying HS and suggest potential therapeutic targets for this challenging condition.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Hidradenitis Suppurativa
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Kruppel-Like Transcription Factors
  • SOX9 Transcription Factor
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
• Source:
  The British Journal of Dermatology, 2025, v. 193, no. 5
• DOI:
  https://doi.org/10.1093/bjd/ljaf277
• ISSN:
  0007-0963 ; 1365-2133
• Pubmed ID:
  40650879
• Pubmed Central ID:
  PMC12279254
• Document Type:
  Text
• Funding:
  S10 OD017985/OD/NIH HHSUnited States/ ; UL1 TR000445/TR/NCATS NIH HHSUnited States/ ; Comprehensive Cancer Center/ ; U19 HL065962/HL/NHLBI NIH HHSUnited States/ ; S10 OD017985/CD/ODCDC CDC HHSUnited States/ ; R01 HD074711/HD/NICHD NIH HHSUnited States/ ; P50 GM115305/GM/NIGMS NIH HHSUnited States/ ; P30 ES010126/ES/NIEHS NIH HHSUnited States/ ; P01 HD031921/HD/NICHD NIH HHSUnited States/ ; UM1 TR004406/TR/NCATS NIH HHSUnited States/ ; R01 HD073342/HD/NICHD NIH HHSUnited States/ ; MH/NIMH NIH HHSUnited States/ ; Common Fund of the Office of the Director of the NIH/ ; R00 HG012222/HG/NHGRI NIH HHSUnited States/ ; S10 RR025141/RR/NCRR NIH HHSUnited States/ ; P30 CA016086/CA/NCI NIH HHSUnited States/ ; R00HG012222/National Human Genome Research Institute of the National Institutes of Health/ ; UL1 TR002489/TR/NCATS NIH HHSUnited States/ ; RC2 GM092618/GM/NIGMS NIH HHSUnited States/ ; S10 OD025092/CD/ODCDC CDC HHSUnited States/ ; National Human Genome Research Institute (NHGRI)/ ; R01 AR083790/AR/NIAMS NIH HHSUnited States/ ; S10 OD025092/OD/NIH HHSUnited States/ ; U01 HG006378/HG/NHGRI NIH HHSUnited States/ ; UL1 RR024975/RR/NCRR NIH HHSUnited States/ ; R01 NS032830/NS/NINDS NIH HHSUnited States/ ; U01 HG004798/HG/NHGRI NIH HHSUnited States/ ; UL1 TR002243/TR/NCATS NIH HHSUnited States/ ; R21 AR075996/AR/NIAMS NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  948-958 (22 pdf pages)
• Volume:
  193
• Issue:
  5
• Download URL:
  https://stacks.cdc.gov/view/cdc/261265/cdc_261265_DS1.pdf
• File Type:
  [PDF - 2.00 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:8ed86618ed4fa44e7d224b88895071f540dc91d28166afe9e9834a10f86be94545ff7218fd7d8f3dc6faf17d377545840dd7f5892148c630888c68b90e377f8f