TY - JOUR
T1 - 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
AU - Kjærsgaard Andersen, Rune
AU - Stefansdottir, Lilja
AU - Riis, Peter Theut
AU - Halldorsson, Gisli
AU - Ferkingstad, Egil
AU - Oddsson, Asmundur
AU - Walters, Bragi
AU - Olafsdottir, Thorunn A.
AU - Rutsdottir, Gudrun
AU - Zachariae, Claus
AU - Thomsen, Simon Francis
AU - Brodersen, Thortsen
AU - Dinh, Khoa Manh
AU - Knowlton, Kirk U.
AU - Knight, Stacey
AU - Nadauld, Lincoln D.
AU - Banasik, Karina
AU - Brunak, Søren
AU - Hansen, Thomas Folkmann
AU - Hjalgrim, Henrik
AU - Sørensen, Erik
AU - Mikkelsen, Chirstina
AU - Ullum, Henrik
AU - Nyegaard, Mette
AU - Bruun, Mie Topholm
AU - Erikstrup, Christian
AU - Ostrowski, Sisse Rye
AU - Eidsmo, Liv
AU - Saunte, Ditte Marie Lindhardt
AU - Sigurgeirsson, Bárdur
AU - Orvar, Kjartar B.
AU - Saemundsdottir, Jona
AU - Melsted, Pall
AU - Norddahl, Gudmundur L.
AU - Sulem, Patrick
AU - Stefansson, Hreinn
AU - Holm, Hilma
AU - Gudbjartsson, Daniel
AU - Thorleifsson, Gudmar
AU - Jonsdottir, Ingileif
AU - Pedersen, Ole Birger Vesterager
AU - Jemec, Gregor Borut Ernst
AU - Stefansson, Kari
N1 - Publisher Copyright:
© 2024 American Academy of Dermatology, Inc.
PY - 2025
Y1 - 2025
N2 - Background: The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood. Objective: To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis. 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. 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. Limitations: Limited racial diversity may prevent identification of sequence variants of particular importance in non-Caucasian populations. Conclusions: These findings demonstrate that genes and pathways involved in epidermal keratinization are the genetic backbone of HS pathology.
AB - Background: The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood. Objective: To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis. 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. 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. Limitations: Limited racial diversity may prevent identification of sequence variants of particular importance in non-Caucasian populations. Conclusions: These findings demonstrate that genes and pathways involved in epidermal keratinization are the genetic backbone of HS pathology.
KW - causality
KW - genetics
KW - genome-wide association study
KW - GWAS
KW - hidradenitis suppurativa
KW - inheritance
KW - NOTCH
KW - Notch signaling
KW - pathway analysis
KW - WNT
KW - Wnt signaling
KW - γ-secretase
U2 - 10.1016/j.jaad.2024.11.050
DO - 10.1016/j.jaad.2024.11.050
M3 - Journal article
C2 - 39645042
AN - SCOPUS:85213974974
JO - American Academy of Dermatology. Journal
JF - American Academy of Dermatology. Journal
SN - 0190-9622
ER -