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

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

163 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	808-812
ページ数	5
ジャーナル	Nature Genetics
巻	45
号	7
DOI	https://doi.org/10.1038/ng.2642
出版ステータス	出版済み - 07-2013
外部発表	はい

All Science Journal Classification (ASJC) codes

遺伝学

文献へのアクセス

10.1038/ng.2642

他のファイルとリンク

引用スタイル

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

@article{f2c6089dc89743fb87cf46dc177e89b7,

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 Lee, {Young Ae} and Andre Franke and Stephan Weidinger",

note = "Funding Information: We thank all individuals with atopic dermatitis, their families, control individuals and clinicians for their participation. We thank T. Wesse, T. Henke, S.S. Sabet, S. Greve, I. Urbach, G. Patone, C. Flachmeier, S. Kolberg and G. Born for expert technical help. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) grant FR 2821/2-1, the German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN; 01GS 0818 and 01GS 0812 to Y.-A.L.) and the PopGen biobank. S.W. is supported by a Heisenberg fellowship of the DFG (WE 2678/7-1). The project received infrastructure support through the DFG Clusters of Excellence {\textquoteleft}Inflammation at Interfaces{\textquoteright}. A.D.I. is supported by the National Children{\textquoteright}s Research Centre, Dublin. A.D.I. and I.M. are supported by the Wellcome Trust (reference 090066/B/09/Z and 092530/Z/10/Z). Funding Information: S. Brand is supported by DFG grant BR1912/6-1 and the Else-Kr{\"o}ner-Fresenius-Stiftung (stipend 2010_EKES.32). We acknowledge US National Institutes of Health grant 1R01CA141743-01 (R.H.D., principal investigator) and the University of Pittsburgh Genomics and Proteomics Core Laboratories for the Immunochip genotyping services. This work was supported by Wellcome Trust Programme and Bioresources grants (090066/B/09/Z and 092530/Z/10/Z) to W.H.I.M. and A.D.I. and a Wellcome Trust Strategic Award (098439/Z/12/Z) to W.H.I.M. Parts of this study were funded by the General Program of National Natural Science Foundation of China (31171224), the Program for New Century Excellent Talents in University (NCET-11-0889), the Science and Technological Foundation of Anhui Province for Outstanding Youth (1108085J10) and a pre-project of State Key Basic Research Program 973 of China (2012CB722404).",

year = "2013",

month = jul,

doi = "10.1038/ng.2642",

language = "English",

volume = "45",

pages = "808--812",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "7",

}

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, YA, 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

TY - JOUR

T1 - High-density genotyping study identifies four new susceptibility loci for atopic dermatitis

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

N1 - Funding Information: We thank all individuals with atopic dermatitis, their families, control individuals and clinicians for their participation. We thank T. Wesse, T. Henke, S.S. Sabet, S. Greve, I. Urbach, G. Patone, C. Flachmeier, S. Kolberg and G. Born for expert technical help. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) grant FR 2821/2-1, the German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN; 01GS 0818 and 01GS 0812 to Y.-A.L.) and the PopGen biobank. S.W. is supported by a Heisenberg fellowship of the DFG (WE 2678/7-1). The project received infrastructure support through the DFG Clusters of Excellence ‘Inflammation at Interfaces’. A.D.I. is supported by the National Children’s Research Centre, Dublin. A.D.I. and I.M. are supported by the Wellcome Trust (reference 090066/B/09/Z and 092530/Z/10/Z). Funding Information: S. Brand is supported by DFG grant BR1912/6-1 and the Else-Kröner-Fresenius-Stiftung (stipend 2010_EKES.32). We acknowledge US National Institutes of Health grant 1R01CA141743-01 (R.H.D., principal investigator) and the University of Pittsburgh Genomics and Proteomics Core Laboratories for the Immunochip genotyping services. This work was supported by Wellcome Trust Programme and Bioresources grants (090066/B/09/Z and 092530/Z/10/Z) to W.H.I.M. and A.D.I. and a Wellcome Trust Strategic Award (098439/Z/12/Z) to W.H.I.M. Parts of this study were funded by the General Program of National Natural Science Foundation of China (31171224), the Program for New Century Excellent Talents in University (NCET-11-0889), the Science and Technological Foundation of Anhui Province for Outstanding Youth (1108085J10) and a pre-project of State Key Basic Research Program 973 of China (2012CB722404).

PY - 2013/7

Y1 - 2013/7

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84879687588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879687588&partnerID=8YFLogxK

U2 - 10.1038/ng.2642

DO - 10.1038/ng.2642

M3 - Article

C2 - 23727859

AN - SCOPUS:84879687588

SN - 1061-4036

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

抄録

All Science Journal Classification (ASJC) codes

文献へのアクセス

他のファイルとリンク

フィンガープリント

引用スタイル