High-density genotyping study identifies four new susceptibility loci for atopic dermatitis

David Ellinghaus; Hansjörg Baurecht; Jorge Esparza-Gordillo; Elke Rodríguez; Anja Matanovic; Ingo Marenholz; Norbert Hübner; Heidi Schaarschmidt; Natalija Novak; Sven Michel; Laura Maintz; Thomas Werfel; Ulf Meyer-Hoffert; Melanie Hotze; Holger Prokisch; Katharina Heim; Christian Herder; Tomomitsu Hirota; Mayumi Tamari; Michiaki Kubo; Atsushi Takahashi; Yusuke Nakamura; Lam C. Tsoi; Philip Stuart; James T. Elder; Liangdan Sun; Xianbo Zuo; Sen Yang; Xuejun Zhang; Per Hoffmann; Markus M. Nöthen; Regina Fölster-Holst; Juliane Winkelmann; Thomas Illig; Bernhard O. Boehm; Richard H. Duerr; Carsten Büning; Stephan Brand; Jürgen Glas; Maeve A. McAleer; Caoimhe M. Fahy; Michael Kabesch; Sara Brown; W H Irwin McLean; Alan D. Irvine; Stefan Schreiber; Young-Ae Lee; Andre Franke; Stephan Weidinger

doi:10.1038/ng.2642

High-density genotyping study identifies four new susceptibility loci for atopic dermatitis

David Ellinghaus, Hansjörg Baurecht, Jorge Esparza-Gordillo, Elke Rodríguez, Anja Matanovic, Ingo Marenholz, Norbert Hübner, Heidi Schaarschmidt, Natalija Novak, Sven Michel, Laura Maintz, Thomas Werfel, Ulf Meyer-Hoffert, Melanie Hotze, Holger Prokisch, Katharina Heim, Christian Herder, Tomomitsu Hirota, Mayumi Tamari, Michiaki KuboAtsushi Takahashi, Yusuke Nakamura, Lam C. Tsoi, Philip Stuart, James T. Elder, Liangdan Sun, Xianbo Zuo, Sen Yang, Xuejun Zhang, Per Hoffmann, Markus M. Nöthen, Regina Fölster-Holst, Juliane Winkelmann, Thomas Illig, Bernhard O. Boehm, Richard H. Duerr, Carsten Büning, Stephan Brand, Jürgen Glas, Maeve A. McAleer, Caoimhe M. Fahy, Michael Kabesch, Sara Brown, W H Irwin McLean, Alan D. Irvine, Stefan Schreiber, Young-Ae Lee, Andre Franke, Stephan Weidinger

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157 Citations (Scopus)

Abstract

Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency. To better define risk variants and identify additional susceptibility loci, we densely genotyped 2,425 German individuals with atopic dermatitis (cases) and 5,449 controls using the Immunochip array followed by replication in 7,196 cases and 15,480 controls from Germany, Ireland, Japan and China. We identified four new susceptibility loci for atopic dermatitis and replicated previous associations. This brings the number of atopic dermatitis risk loci reported in individuals of European ancestry to 11. We estimate that these susceptibility loci together account for 14.4% of the heritability for atopic dermatitis.

Original language	English
Pages (from-to)	808-812
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	7
DOIs	https://doi.org/10.1038/ng.2642
Publication status	Published - Jul 2013

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10.1038/ng.2642

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)
Barton, G. (Investigator), Campbell, P. (Investigator), Hickerson, R. (Investigator), Leigh, I. (Investigator), McLean, I. (Investigator) & Wyatt, P. (Investigator)
1/08/12 → 30/04/19
Project: Research
Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)
Barton, G. (Investigator) & McLean, I. (Investigator)
1/10/10 → 28/02/14
Project: Research
Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)
McLean, I. (Investigator)
1/03/10 → 28/02/14
Project: Research

Cite this

Ellinghaus, D., Baurecht, H., Esparza-Gordillo, J., Rodríguez, E., Matanovic, A., Marenholz, I., Hübner, N., Schaarschmidt, H., Novak, N., Michel, S., Maintz, L., Werfel, T., Meyer-Hoffert, U., Hotze, M., Prokisch, H., Heim, K., Herder, C., Hirota, T., Tamari, M., ... Weidinger, S. (2013). High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nature Genetics, 45(7), 808-812. https://doi.org/10.1038/ng.2642

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title = "High-density genotyping study identifies four new susceptibility loci for atopic dermatitis",

abstract = "Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency. To better define risk variants and identify additional susceptibility loci, we densely genotyped 2,425 German individuals with atopic dermatitis (cases) and 5,449 controls using the Immunochip array followed by replication in 7,196 cases and 15,480 controls from Germany, Ireland, Japan and China. We identified four new susceptibility loci for atopic dermatitis and replicated previous associations. This brings the number of atopic dermatitis risk loci reported in individuals of European ancestry to 11. We estimate that these susceptibility loci together account for 14.4% of the heritability for atopic dermatitis.",

author = "David Ellinghaus and Hansj{\"o}rg Baurecht and Jorge Esparza-Gordillo and Elke Rodr{\'i}guez and Anja Matanovic and Ingo Marenholz and Norbert H{\"u}bner and Heidi Schaarschmidt and Natalija Novak and Sven Michel and Laura Maintz and Thomas Werfel and Ulf Meyer-Hoffert and Melanie Hotze and Holger Prokisch and Katharina Heim and Christian Herder and Tomomitsu Hirota and Mayumi Tamari and Michiaki Kubo and Atsushi Takahashi and Yusuke Nakamura and Tsoi, {Lam C.} and Philip Stuart and Elder, {James T.} and Liangdan Sun and Xianbo Zuo and Sen Yang and Xuejun Zhang and Per Hoffmann and N{\"o}then, {Markus M.} and Regina F{\"o}lster-Holst and Juliane Winkelmann and Thomas Illig and Boehm, {Bernhard O.} and Duerr, {Richard H.} and Carsten B{\"u}ning and Stephan Brand and J{\"u}rgen Glas and McAleer, {Maeve A.} and Fahy, {Caoimhe M.} and Michael Kabesch and Sara Brown and McLean, {W H Irwin} and Irvine, {Alan D.} and Stefan Schreiber and Young-Ae Lee and Andre Franke and Stephan Weidinger",

year = "2013",

month = jul,

doi = "10.1038/ng.2642",

language = "English",

volume = "45",

pages = "808--812",

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Ellinghaus, D, Baurecht, H, Esparza-Gordillo, J, Rodríguez, E, Matanovic, A, Marenholz, I, Hübner, N, Schaarschmidt, H, Novak, N, Michel, S, Maintz, L, Werfel, T, Meyer-Hoffert, U, Hotze, M, Prokisch, H, Heim, K, Herder, C, Hirota, T, Tamari, M, Kubo, M, Takahashi, A, Nakamura, Y, Tsoi, LC, Stuart, P, Elder, JT, Sun, L, Zuo, X, Yang, S, Zhang, X, Hoffmann, P, Nöthen, MM, Fölster-Holst, R, Winkelmann, J, Illig, T, Boehm, BO, Duerr, RH, Büning, C, Brand, S, Glas, J, McAleer, MA, Fahy, CM, Kabesch, M, Brown, S, McLean, WHI, Irvine, AD, Schreiber, S, Lee, Y-A, Franke, A & Weidinger, S 2013, 'High-density genotyping study identifies four new susceptibility loci for atopic dermatitis', Nature Genetics, vol. 45, no. 7, pp. 808-812. https://doi.org/10.1038/ng.2642

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AU - Ellinghaus, David

AU - Baurecht, Hansjörg

AU - Esparza-Gordillo, Jorge

AU - Rodríguez, Elke

AU - Matanovic, Anja

AU - Marenholz, Ingo

AU - Hübner, Norbert

AU - Schaarschmidt, Heidi

AU - Novak, Natalija

AU - Michel, Sven

AU - Maintz, Laura

AU - Werfel, Thomas

AU - Meyer-Hoffert, Ulf

AU - Hotze, Melanie

AU - Prokisch, Holger

AU - Heim, Katharina

AU - Herder, Christian

AU - Hirota, Tomomitsu

AU - Tamari, Mayumi

AU - Kubo, Michiaki

AU - Takahashi, Atsushi

AU - Nakamura, Yusuke

AU - Tsoi, Lam C.

AU - Stuart, Philip

AU - Elder, James T.

AU - Sun, Liangdan

AU - Zuo, Xianbo

AU - Yang, Sen

AU - Zhang, Xuejun

AU - Hoffmann, Per

AU - Nöthen, Markus M.

AU - Fölster-Holst, Regina

AU - Winkelmann, Juliane

AU - Illig, Thomas

AU - Boehm, Bernhard O.

AU - Duerr, Richard H.

AU - Büning, Carsten

AU - Brand, Stephan

AU - Glas, Jürgen

AU - McAleer, Maeve A.

AU - Fahy, Caoimhe M.

AU - Kabesch, Michael

AU - Brown, Sara

AU - McLean, W H Irwin

AU - Irvine, Alan D.

AU - Schreiber, Stefan

AU - Lee, Young-Ae

AU - Franke, Andre

AU - Weidinger, Stephan

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AB - Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency. To better define risk variants and identify additional susceptibility loci, we densely genotyped 2,425 German individuals with atopic dermatitis (cases) and 5,449 controls using the Immunochip array followed by replication in 7,196 cases and 15,480 controls from Germany, Ireland, Japan and China. We identified four new susceptibility loci for atopic dermatitis and replicated previous associations. This brings the number of atopic dermatitis risk loci reported in individuals of European ancestry to 11. We estimate that these susceptibility loci together account for 14.4% of the heritability for atopic dermatitis.

U2 - 10.1038/ng.2642

DO - 10.1038/ng.2642

M3 - Article

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VL - 45

SP - 808

EP - 812

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

High-density genotyping study identifies four new susceptibility loci for atopic dermatitis

Abstract

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Projects

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

Cite this