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

Disease areas:

• infections

Last updated:

2 July 2025

Author(s):

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

Publish date:

5 December 2024

Journal:

Journal of the American Academy of Dermatology

PubMed ID:

39645042

DOI:

10.1016/j.jaad.2024.11.050

Abstract

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.