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

被引：0

作者：

Andersen, Rune Kjaersgaard ^{[1
,2
]}

Stefansdottir, Lilja ^{[3
]}

Riis, Peter Theut ^{[1
]}

Halldorsson, Gisli ^{[3
,4
]}

Ferkingstad, Egil ^{[3
]}

Oddsson, Asmundur ^{[3
]}

Walters, Bragi ^{[3
]}

Olafsdottir, Thorunn A. ^{[3
,5
]}

Rutsdottir, Gudrun ^{[3
]}

Zachariae, Claus ^{[6
]}

Thomsen, Simon Francis ^{[7
]}

Brodersen, Thortsen ^{[8
]}

Dinh, Khoa Manh ^{[9
,10
]}

Knowlton, Kirk U. ^{[11
,12
]}

Knight, Stacey ^{[11
,12
]}

Nadauld, Lincoln D. ^{[13
]}

Banasik, Karina ^{[14
]}

Brunak, Soren ^{[14
]}

Hansen, Thomas Folkmann ^{[15
]}

Hjalgrim, Henrik ^{[16
,17
,18
,19
]}

Sorensen, Erik ^{[9
]}

Mikkelsen, Chirstina ^{[20
]}

Ullum, Henrik ^{[21
]}

Nyegaard, Mette ^{[22
]}

Bruun, Mie Topholm ^{[23
]}

Erikstrup, Christian ^{[10
,19
,24
]}

Ostrowski, Sisse Rye ^{[19
]}

Eidsmo, Liv ^{[2
]}

Saunte, Ditte Marie Lindhardt ^{[1
,19
]}

Sigurgeirsson, Bardur ^{[25
]}

Orvar, Kjartar B. ^{[26
]}

Saemundsdottir, Jona ^{[3
]}

Melsted, Pall ^{[3
]}

Norddahl, Gudmundur L. ^{[3
]}

Sulem, Patrick ^{[3
]}

Stefansson, Hreinn ^{[3
]}

Holm, Hilma ^{[3
]}

Gudbjartsson, Daniel ^{[3
,4
]}

Thorleifsson, Gudmar ^{[3
]}

Jonsdottir, Ingileif ^{[3
,5
]}

Pedersen, Ole Birger Vesterager ^{[7
,19
]}

Jemec, Gregor Borut Ernst ^{[1
,19
]}

Stefansson, Kari ^{[3
,5
]}

机构：

[1] Univ Copenhagen, Roskilde Hosp, Roskilde, Denmark

[2] Univ Copenhagen, Dept Immunol & Microbiol, LEO Fdn, Skin Immunol Res Ctr, Copenhagen, Denmark

[3] Amgen Inc, deCODE Genet, Reykjavik, Iceland

[4] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland

[5] Univ Iceland, Fac Med, Reykjavik, Iceland

[6] Univ Copenhagen, Herlev & Gentofte Hosp, Dept Dermatol & Allergy, Hellerup, Denmark

[7] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, Copenhagen, Denmark

[8] Zealand Univ Hosp, Dept Clin Immunol, Koge, Denmark

[9] Copenhagen Univ Hosp, Dept Clin Immunol, Rigshosp, Copenhagen, Denmark

[10] Aarhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark

[11] Intermt Heart Inst, Intermt Med Ctr, Salt Lake City, UT USA

[12] Univ Utah, Sch Med, Salt Lake City, UT USA

[13] Intermt Healthcare, Precis Genom, St George, UT USA

[14] Univ Copenhagen, Novo Nord Fdn Ctr Prot Res, Fac Hlth & Med Sci, Copenhagen, Denmark

[15] Copenhagen Univ Hosp, Danish Headache Ctr, Dept Neurol, Rigshosp Glostrup, Copenhagen, Denmark

[16] Danish Canc Soc, Danish Canc Soc Res Ctr, Copenhagen, Denmark

[17] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

[18] Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark

[19] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark

[20] Univ Copenhagen, Novo Nord Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark

[21] Statens Serum Inst, Copenhagen, Denmark

[22] Aalborg Univ, Dept Hlth Sci & Technol, Gistrup, Denmark

[23] Odense Univ Hosp, Dept Clin Immunol, Clin Immunol Res Unit, Odense, Denmark

[24] Aarhus Univ, Dept Clin Med, Aarhus, Denmark

[25] Univ Iceland, Fac Med, Dept Dermatol, Reykjavik, Iceland

[26] Landspitali Natl Univ Hosp Iceland, Med, Reykjavik, Iceland

来源：

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY | 2025年 / 92卷 / 04期

关键词：

gamma-secretase; causality; genetics; genome-wide association study; GWAS; hidradenitis suppurativa; inheritance; NOTCH; Notch signaling; pathway analysis; WNT; Wnt signaling; GAMMA-SECRETASE; KERATINOCYTE DIFFERENTIATION; EXPRESSION; MUTATIONS; DISEASE; SKIN; GENE; CONTRIBUTES; PREVALENCE; NCSTN;

D O I：

10.1016/j.jaad.2024.11.050

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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/beta-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.

引用

页码：761 / 772

页数：12

共 22 条

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