| Title: | A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways |
| Journal: | Journal of the American Academy of Dermatology |
| Published: | 5 Dec 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39645042/ |
| DOI: | https://doi.org/10.1016/j.jaad.2024.11.050 |
Publication 14672
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Abstract
BACKGROUND: The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood.</p>
OBJECTIVE: To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis.</p>
METHODS: A genome-wide association meta-analysis of 4814 HS cases (Denmark: 1977; Iceland: 1266; Finland: 800; UK: 569; and US: 202) and 1.2 million controls, searching for sequence variants associated with HS.</p>
RESULTS: We found 8 independent sequence variants associating with HS, 6 common and 2 rare (frequency <1%). Four associations point to candidate causal genes, NCSTN, PSENEN, WNT10A, and TMED10, that all map to the Notch and Wnt/β-catenin signaling pathways, involved in epidermal keratinization.</p>
LIMITATIONS: Limited racial diversity may prevent identification of sequence variants of particular importance in non-Caucasian populations.</p>
CONCLUSIONS: These findings demonstrate that genes and pathways involved in epidermal keratinization are the genetic backbone of HS pathology.</p>
12 Keywords
- Amyloid Precursor Protein Secretases
- Genetic Predisposition to Disease
- Genetic Variation
- Genome-Wide Association Study
- Hidradenitis Suppurativa
- Humans
- Male
- Membrane Glycoproteins
- Polymorphism, Single Nucleotide
- Receptors, Notch
- Wnt Proteins
- Wnt Signaling Pathway
43 Authors
- Rune Kjærsgaard Andersen
- Lilja Stefansdottir
- Peter Theut Riis
- Gisli Halldorsson
- Egil Ferkingstad
- Asmundur Oddsson
- Bragi Walters
- Thorunn A Olafsdottir
- Gudrun Rutsdottir
- Claus Zachariae
- Simon Francis Thomsen
- Thortsen Brodersen
- Khoa Manh Dinh
- Kirk U Knowlton
- Stacey Knight
- Lincoln D Nadauld
- Karina Banasik
- Søren Brunak
- Thomas Folkmann Hansen
- Henrik Hjalgrim
- Erik Sørensen
- Chirstina Mikkelsen
- Henrik Ullum
- Mette Nyegaard
- Mie Topholm Bruun
- Christian Erikstrup
- Sisse Rye Ostrowski
- Liv Eidsmo
- Ditte Marie Lindhardt Saunte
- Bárdur Sigurgeirsson
- Kjartar B Orvar
- Jona Saemundsdottir
- Pall Melsted
- Gudmundur L Norddahl
- Patrick Sulem
- Hreinn Stefansson
- Hilma Holm
- Daniel Gudbjartsson
- Gudmar Thorleifsson
- Ingileif Jonsdottir
- Ole Birger Vesterager Pedersen
- Gregor Borut Ernst Jemec
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 56270 | Evaluating and comparing sequence variant associations between the deCODE and UK Biobank datasets across a range of human traits |
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