Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Lavinia Paternoster; Marie Standl; Chih Mei Chen; Adaikalavan Ramasamy; Klaus Bøpnnelykke; Liesbeth Duijts; Manuel A. Ferreira; Alexessander Couto Alves; Jacob P. Thyssen; Eva Albrecht; Hansjörg Baurecht; Bjarke Feenstra; Patrick M.A. Sleiman; Pirro Hysi; Nicole M. Warrington; Ivan Curjuric; Ronny Myhre; John A. Curtin; Maria M. Groen-Blokhuis; Marjan Kerkhof; Annika Sääf; Andre Franke; David Ellinghaus; Regina Fölster-Holst; Emmanouil Dermitzakis; Stephen B. Montgomery; Holger Prokisch; Katharina Heim; Anna Liisa Hartikainen; Anneli Pouta; Juha Pekkanen; Alexandra I.F. Blakemore; Jessica L. Buxton; Marika Kaakinen; David L. Duffy; Pamela A. Madden; Andrew C. Heath; Grant W. Montgomery; Philip J. Thompson; Melanie C. Matheson; Peter Le Souëf; Beate St Pourcain; George Davey Smith; John Henderson; John P. Kemp; Nicholas J. Timpson; Panos Deloukas; Susan M. Ring; H. Erich Wichmann; Martina Müller-Nurasyid; Natalija Novak; Norman Klopp; Elke Rodríguez; Wendy McArdle; Allan Linneberg; Torkil Menné; Ellen A. Nohr; Albert Hofman; André G. Uitterlinden; Cornélia M. Van Duijn; Fernando Rivadeneira; Johan C. De Jongste; Ralf J.P. Van Der Valk; Matthias Wjst; Rain Jogi; Frank Geller; Heather A. Boyd; Jeffrey C. Murray; Cecilia Kim; Frank Mentch; Michael March; Massimo Mangino; Tim D. Spector; Veronique Bataille; Craig E. Pennell; Patrick G. Holt; Peter Sly; Carla M.T. Tiesler; Elisabeth Thiering; Thomas Illig; Medea Imboden; Wenche Nystad; Angela Simpson; Jouke Jan Hottenga; Dirkje Postma; Gerard H. Koppelman; Henriette A. Smit; Cilla Söderhäll; Bo Chawes; Eskil Kreiner-Møpller; Hans Bisgaard; Erik Melén; Dorret I. Boomsma; Adnan Custovic; Bo Jacobsson; Nicole M. Probst-Hensch; Lyle J. Palmer; Daniel Glass; Hakon Hakonarson; Mads Melbye; Deborah L. Jarvis; Vincent W.V. Jaddoe; Christian Gieger; David P. Strachan; Nicholas G. Martin; Marjo Riitta Jarvelin; Joachim Heinrich; David M. Evans; Stephan Weidinger

doi:10.1038/ng.1017

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Lavinia Paternoster^*
, Marie Standl
, Chih Mei Chen
, Adaikalavan Ramasamy
, Klaus Bøpnnelykke
, Liesbeth Duijts
, Manuel A. Ferreira
, Alexessander Couto Alves
, Jacob P. Thyssen
, Eva Albrecht
, Hansjörg Baurecht
, Bjarke Feenstra
, Patrick M.A. Sleiman
, Pirro Hysi
, Nicole M. Warrington
, Ivan Curjuric
, Ronny Myhre
, John A. Curtin
, Maria M. Groen-Blokhuis
, Marjan Kerkhof

Annika Sääf, Andre Franke, David Ellinghaus, Regina Fölster-Holst, Emmanouil Dermitzakis, Stephen B. Montgomery, Holger Prokisch, Katharina Heim, Anna Liisa Hartikainen, Anneli Pouta, Juha Pekkanen, Alexandra I.F. Blakemore, Jessica L. Buxton, Marika Kaakinen, David L. Duffy, Pamela A. Madden, Andrew C. Heath, Grant W. Montgomery, Philip J. Thompson, Melanie C. Matheson, Peter Le Souëf, Beate St Pourcain, George Davey Smith, John Henderson, John P. Kemp, Nicholas J. Timpson, Panos Deloukas, Susan M. Ring, H. Erich Wichmann, Martina Müller-Nurasyid, Natalija Novak, Norman Klopp, Elke Rodríguez, Wendy McArdle, Allan Linneberg, Torkil Menné, Ellen A. Nohr, Albert Hofman, André G. Uitterlinden, Cornélia M. Van Duijn, Fernando Rivadeneira, Johan C. De Jongste, Ralf J.P. Van Der Valk, Matthias Wjst, Rain Jogi, Frank Geller, Heather A. Boyd, Jeffrey C. Murray, Cecilia Kim, Frank Mentch, Michael March, Massimo Mangino, Tim D. Spector, Veronique Bataille, Craig E. Pennell, Patrick G. Holt, Peter Sly, Carla M.T. Tiesler, Elisabeth Thiering, Thomas Illig, Medea Imboden, Wenche Nystad, Angela Simpson, Jouke Jan Hottenga, Dirkje Postma, Gerard H. Koppelman, Henriette A. Smit, Cilla Söderhäll, Bo Chawes, Eskil Kreiner-Møpller, Hans Bisgaard, Erik Melén, Dorret I. Boomsma, Adnan Custovic, Bo Jacobsson, Nicole M. Probst-Hensch, Lyle J. Palmer, Daniel Glass, Hakon Hakonarson, Mads Melbye, Deborah L. Jarvis, Vincent W.V. Jaddoe, Christian Gieger, David P. Strachan, Nicholas G. Martin, Marjo Riitta Jarvelin, Joachim Heinrich, David M. Evans, Stephan Weidinger

^*Corresponding author for this work

University of Bristol
Helmholtz Zentrum München - German Research Center for Environmental Health
Hannover Medical School
Imperial College London
Guy's and St Thomas' NHS Foundation Trust
University of Copenhagen
Erasmus University Rotterdam
Queensland Institute of Medical Research
Technical University of Munich
University Hospital of Schleswig-Holstein
Statens Serum Institut
Children's Hospital of Philadelphia
King's College London
University of Western Australia
Swiss Tropical and Public Health Institute
University of Basel
Norwegian Institute of Public Health
University of Manchester
Vrije Universiteit Amsterdam
University of Groningen
Karolinska Institutet
Kiel University
University of Geneva
Wellcome Trust Sanger Institute
University of Oulu
National Institute for Health and Welfare
University of Eastern Finland
Washington University St. Louis
Lung Institute of Western Australia
University of Melbourne
Princess Margaret Hospital for Children
Ludwig Maximilian University of Munich
Aarhus University
Tartu University Hospital
University of Iowa
Telethon Kids Institute
University of Queensland
University of Bonn
Utrecht University
Sahlgrenska University Hospital
University of Toronto
University of Pennsylvania
St. George's University of London

Research output: Contribution to journal › Article › peer-review

304 Citations (Scopus)

Abstract

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10 ^-13) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10 ^-9), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10 ^-8). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.

Original language	English
Pages (from-to)	187-192
Number of pages	6
Journal	Nature Genetics
Volume	44
Issue number	2
DOIs	https://doi.org/10.1038/ng.1017
Publication status	Published - 25 Dec 2012
Externally published	Yes

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Paternoster, L., Standl, M., Chen, C. M., Ramasamy, A., Bøpnnelykke, K., Duijts, L., Ferreira, M. A., Alves, A. C., Thyssen, J. P., Albrecht, E., Baurecht, H., Feenstra, B., Sleiman, P. M. A., Hysi, P., Warrington, N. M., Curjuric, I., Myhre, R., Curtin, J. A., Groen-Blokhuis, M. M., ... Weidinger, S. (2012). Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature Genetics, 44(2), 187-192. https://doi.org/10.1038/ng.1017

@article{39010d9f41aa4daaa4a3d9df291cd43f,

title = "Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis",

abstract = "Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10 -13) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10 -9), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10 -8). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.",

author = "Lavinia Paternoster and Marie Standl and Chen, \{Chih Mei\} and Adaikalavan Ramasamy and Klaus B{\o}pnnelykke and Liesbeth Duijts and Ferreira, \{Manuel A.\} and Alves, \{Alexessander Couto\} and Thyssen, \{Jacob P.\} and Eva Albrecht and Hansj{\"o}rg Baurecht and Bjarke Feenstra and Sleiman, \{Patrick M.A.\} and Pirro Hysi and Warrington, \{Nicole M.\} and Ivan Curjuric and Ronny Myhre and Curtin, \{John A.\} and Groen-Blokhuis, \{Maria M.\} and Marjan Kerkhof and Annika S{\"a}{\"a}f and Andre Franke and David Ellinghaus and Regina F{\"o}lster-Holst and Emmanouil Dermitzakis and Montgomery, \{Stephen B.\} and Holger Prokisch and Katharina Heim and Hartikainen, \{Anna Liisa\} and Anneli Pouta and Juha Pekkanen and Blakemore, \{Alexandra I.F.\} and Buxton, \{Jessica L.\} and Marika Kaakinen and Duffy, \{David L.\} and Madden, \{Pamela A.\} and Heath, \{Andrew C.\} and Montgomery, \{Grant W.\} and Thompson, \{Philip J.\} and Matheson, \{Melanie C.\} and \{Le Sou{\"e}f\}, Peter and Pourcain, \{Beate St\} and Smith, \{George Davey\} and John Henderson and Kemp, \{John P.\} and Timpson, \{Nicholas J.\} and Panos Deloukas and Ring, \{Susan M.\} and Wichmann, \{H. Erich\} and Martina M{\"u}ller-Nurasyid and Natalija Novak and Norman Klopp and Elke Rodr{\'i}guez and Wendy McArdle and Allan Linneberg and Torkil Menn{\'e} and Nohr, \{Ellen A.\} and Albert Hofman and Uitterlinden, \{Andr{\'e} G.\} and \{Van Duijn\}, \{Corn{\'e}lia M.\} and Fernando Rivadeneira and \{De Jongste\}, \{Johan C.\} and \{Van Der Valk\}, \{Ralf J.P.\} and Matthias Wjst and Rain Jogi and Frank Geller and Boyd, \{Heather A.\} and Murray, \{Jeffrey C.\} and Cecilia Kim and Frank Mentch and Michael March and Massimo Mangino and Spector, \{Tim D.\} and Veronique Bataille and Pennell, \{Craig E.\} and Holt, \{Patrick G.\} and Peter Sly and Tiesler, \{Carla M.T.\} and Elisabeth Thiering and Thomas Illig and Medea Imboden and Wenche Nystad and Angela Simpson and Hottenga, \{Jouke Jan\} and Dirkje Postma and Koppelman, \{Gerard H.\} and Smit, \{Henriette A.\} and Cilla S{\"o}derh{\"a}ll and Bo Chawes and Eskil Kreiner-M{\o}pller and Hans Bisgaard and Erik Mel{\'e}n and Boomsma, \{Dorret I.\} and Adnan Custovic and Bo Jacobsson and Probst-Hensch, \{Nicole M.\} and Palmer, \{Lyle J.\} and Daniel Glass and Hakon Hakonarson and Mads Melbye and Jarvis, \{Deborah L.\} and Jaddoe, \{Vincent W.V.\} and Christian Gieger and Strachan, \{David P.\} and Martin, \{Nicholas G.\} and Jarvelin, \{Marjo Riitta\} and Joachim Heinrich and Evans, \{David M.\} and Stephan Weidinger",

year = "2012",

month = dec,

day = "25",

doi = "10.1038/ng.1017",

language = "English",

volume = "44",

pages = "187--192",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "2",

}

Paternoster, L, Standl, M, Chen, CM, Ramasamy, A, Bøpnnelykke, K, Duijts, L, Ferreira, MA, Alves, AC, Thyssen, JP, Albrecht, E, Baurecht, H, Feenstra, B, Sleiman, PMA, Hysi, P, Warrington, NM, Curjuric, I, Myhre, R, Curtin, JA, Groen-Blokhuis, MM, Kerkhof, M, Sääf, A, Franke, A, Ellinghaus, D, Fölster-Holst, R, Dermitzakis, E, Montgomery, SB, Prokisch, H, Heim, K, Hartikainen, AL, Pouta, A, Pekkanen, J, Blakemore, AIF, Buxton, JL, Kaakinen, M, Duffy, DL, Madden, PA, Heath, AC, Montgomery, GW, Thompson, PJ, Matheson, MC, Le Souëf, P, Pourcain, BS, Smith, GD, Henderson, J, Kemp, JP, Timpson, NJ, Deloukas, P, Ring, SM, Wichmann, HE, Müller-Nurasyid, M, Novak, N, Klopp, N, Rodríguez, E, McArdle, W, Linneberg, A, Menné, T, Nohr, EA, Hofman, A, Uitterlinden, AG, Van Duijn, CM, Rivadeneira, F, De Jongste, JC, Van Der Valk, RJP, Wjst, M, Jogi, R, Geller, F, Boyd, HA, Murray, JC, Kim, C, Mentch, F, March, M, Mangino, M, Spector, TD, Bataille, V, Pennell, CE, Holt, PG, Sly, P, Tiesler, CMT, Thiering, E, Illig, T, Imboden, M, Nystad, W, Simpson, A, Hottenga, JJ, Postma, D, Koppelman, GH, Smit, HA, Söderhäll, C, Chawes, B, Kreiner-Møpller, E, Bisgaard, H, Melén, E, Boomsma, DI, Custovic, A, Jacobsson, B, Probst-Hensch, NM, Palmer, LJ, Glass, D, Hakonarson, H, Melbye, M, Jarvis, DL, Jaddoe, VWV, Gieger, C, Strachan, DP, Martin, NG, Jarvelin, MR, Heinrich, J, Evans, DM & Weidinger, S 2012, 'Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis', Nature Genetics, vol. 44, no. 2, pp. 187-192. https://doi.org/10.1038/ng.1017

TY - JOUR

T1 - Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

AU - Paternoster, Lavinia

AU - Standl, Marie

AU - Chen, Chih Mei

AU - Ramasamy, Adaikalavan

AU - Bøpnnelykke, Klaus

AU - Duijts, Liesbeth

AU - Ferreira, Manuel A.

AU - Alves, Alexessander Couto

AU - Thyssen, Jacob P.

AU - Albrecht, Eva

AU - Baurecht, Hansjörg

AU - Feenstra, Bjarke

AU - Sleiman, Patrick M.A.

AU - Hysi, Pirro

AU - Warrington, Nicole M.

AU - Curjuric, Ivan

AU - Myhre, Ronny

AU - Curtin, John A.

AU - Groen-Blokhuis, Maria M.

AU - Kerkhof, Marjan

AU - Sääf, Annika

AU - Franke, Andre

AU - Ellinghaus, David

AU - Fölster-Holst, Regina

AU - Dermitzakis, Emmanouil

AU - Montgomery, Stephen B.

AU - Prokisch, Holger

AU - Heim, Katharina

AU - Hartikainen, Anna Liisa

AU - Pouta, Anneli

AU - Pekkanen, Juha

AU - Blakemore, Alexandra I.F.

AU - Buxton, Jessica L.

AU - Kaakinen, Marika

AU - Duffy, David L.

AU - Madden, Pamela A.

AU - Heath, Andrew C.

AU - Montgomery, Grant W.

AU - Thompson, Philip J.

AU - Matheson, Melanie C.

AU - Le Souëf, Peter

AU - Pourcain, Beate St

AU - Smith, George Davey

AU - Henderson, John

AU - Kemp, John P.

AU - Timpson, Nicholas J.

AU - Deloukas, Panos

AU - Ring, Susan M.

AU - Wichmann, H. Erich

AU - Müller-Nurasyid, Martina

AU - Novak, Natalija

AU - Klopp, Norman

AU - Rodríguez, Elke

AU - McArdle, Wendy

AU - Linneberg, Allan

AU - Menné, Torkil

AU - Nohr, Ellen A.

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - Van Duijn, Cornélia M.

AU - Rivadeneira, Fernando

AU - De Jongste, Johan C.

AU - Van Der Valk, Ralf J.P.

AU - Wjst, Matthias

AU - Jogi, Rain

AU - Geller, Frank

AU - Boyd, Heather A.

AU - Murray, Jeffrey C.

AU - Kim, Cecilia

AU - Mentch, Frank

AU - March, Michael

AU - Mangino, Massimo

AU - Spector, Tim D.

AU - Bataille, Veronique

AU - Pennell, Craig E.

AU - Holt, Patrick G.

AU - Sly, Peter

AU - Tiesler, Carla M.T.

AU - Thiering, Elisabeth

AU - Illig, Thomas

AU - Imboden, Medea

AU - Nystad, Wenche

AU - Simpson, Angela

AU - Hottenga, Jouke Jan

AU - Postma, Dirkje

AU - Koppelman, Gerard H.

AU - Smit, Henriette A.

AU - Söderhäll, Cilla

AU - Chawes, Bo

AU - Kreiner-Møpller, Eskil

AU - Bisgaard, Hans

AU - Melén, Erik

AU - Boomsma, Dorret I.

AU - Custovic, Adnan

AU - Jacobsson, Bo

AU - Probst-Hensch, Nicole M.

AU - Palmer, Lyle J.

AU - Glass, Daniel

AU - Hakonarson, Hakon

AU - Melbye, Mads

AU - Jarvis, Deborah L.

AU - Jaddoe, Vincent W.V.

AU - Gieger, Christian

AU - Strachan, David P.

AU - Martin, Nicholas G.

AU - Jarvelin, Marjo Riitta

AU - Heinrich, Joachim

AU - Evans, David M.

AU - Weidinger, Stephan

PY - 2012/12/25

Y1 - 2012/12/25

N2 - Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10 -13) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10 -9), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10 -8). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.

AB - Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10 -13) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10 -9), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10 -8). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.

UR - https://www.scopus.com/pages/publications/84856283235

U2 - 10.1038/ng.1017

DO - 10.1038/ng.1017

M3 - Article

C2 - 22197932

AN - SCOPUS:84856283235

SN - 1061-4036

VL - 44

SP - 187

EP - 192

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

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