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.
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Kjærsgaard Andersen Rune, Stefansdottir Lilja, Riis Peter Theut, Halldorsson Gisli, Ferkingstad Egil, Oddsson Asmundur, Walters Bragi, Olafsdottir Thorunn A, Rutsdottir Gudrun, Zachariae Claus, Thomsen Simon Francis, Brodersen Thortsen, Dinh Khoa Manh, Knowlton Kirk U, Knight Stacey, Nadauld Lincoln D, Banasik Karina, Brunak Søren, Hansen Thomas Folkmann, Hjalgrim Henrik, Sørensen Erik, Mikkelsen Chirstina, Ullum Henrik, Nyegaard Mette, Bruun Mie Topholm, Erikstrup Christian, Ostrowski Sisse Rye, Eidsmo Liv, Saunte Ditte Marie Lindhardt, Sigurgeirsson Bárdur, Orvar Kjartar B, Saemundsdottir Jona, Melsted Pall, Norddahl Gudmundur L, Sulem Patrick, Stefansson Hreinn, Holm Hilma, Gudbjartsson Daniel, Thorleifsson Gudmar, Jonsdottir Ingileif, Pedersen Ole Birger Vesterager, Jemec Gregor Borut Ernst, Stefansson Kari
Аннотация
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.