Медицинская библиотека · Journal of the American Academy of Dermatology · 2024

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.

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

СтатьяМетаанализПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: 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. 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 of the American Academy of Dermatology. 2024. DOI: 10.1016/j.jaad.2024.11.050.

Предметные рубрики MeSH

Hidradenitis Suppurativa Humans Genome-Wide Association Study Wnt Signaling Pathway Receptors, Notch Wnt Proteins Genetic Predisposition to Disease Amyloid Precursor Protein Secretases Membrane Proteins Polymorphism, Single Nucleotide Male Female Membrane Glycoproteins

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