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 Bonnelykke; Liesbeth Duijts; Manuel A. Ferreira; Alexessander Couto Alves; Jacob P. Thyssen; Eva Albrecht; Hansjoerg 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 Saaf; Andre Franke; David Ellinghaus; Regina Foelster-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 Souef; Beate St Pourcain; George Davey Smith; John Henderson; John P. Kemp; Nicholas J. Timpson; Panos Deloukas; Susan M. Ring; H-Erich Wichmann; Martina Mueller-Nurasyid; Natalija Novak; Norman Klopp; Elke Rodriguez; Wendy McArdle; Allan Linneberg; Torkil Menne; Ellen A. Nohr; Albert Hofman; Andre G. Uitterlinden; Cornelia M. van Duijin; 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 Soderhall; Bo Chawes; Eskil Kreiner-Moller; Hans Bisgaard; Erik Melen; 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; Australian Asthma Genetics Consort

doi:10.1038/ng.1017

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

Journal article

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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 Bonnelykke, Liesbeth Duijts, Manuel A. Ferreira, Alexessander Couto Alves, Jacob P. Thyssen, Eva Albrecht, …

Nature genetics, Vol.44(2), pp.187-192

01/02/2012

DOI: https://doi.org/10.1038/ng.1017

PMCID: PMC3272375

PMID: 22197932

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 x 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 x 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.

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Title: Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
Creators - without role: Lavinia Paternoster - University of Bristol
Marie Standl - Helmholtz Zentrum München
Chih-Mei Chen - Supreme Council Of Health
Adaikalavan Ramasamy - University of London
Klaus Bonnelykke - University of Copenhagen
Liesbeth Duijts - Erasmus MC
Manuel A. Ferreira - College Station Medical Center
Alexessander Couto Alves - University of London
Jacob P. Thyssen - University of Copenhagen
Eva Albrecht - Helmholtz Zentrum München
Hansjoerg Baurecht - Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany
Bjarke Feenstra - Veterinary Biological and Research Institute
Patrick M. A. Sleiman - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
Pirro Hysi - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Nicole M. Warrington - University of Western Australia
Ivan Curjuric - Swiss Tropical and Public Health Institute
Ronny Myhre - Norwegian Inst Publ Hlth, Div Epidemiol, Dept Genes & Environm, Oslo, Norway
John A. Curtin - Natl Hlth Serv Fdn Trust, Univ Manchester, Univ S Manchester Hosp, Manchester Acad Hlth Sci Ctr,NIHR,Translat Res Fa, Manchester, Lancs, England
Maria M. Groen-Blokhuis - University of Amsterdam
Marjan Kerkhof - University of Groningen
Annika Saaf - Karolinska Institutet
Andre Franke - Univ Kiel, Inst Clin Mol Biol, Kiel, Germany
David Ellinghaus - Univ Kiel, Inst Clin Mol Biol, Kiel, Germany
Regina Foelster-Holst - Univ Hosp Schleswig Holstein, Dept Dermatol Allergol & Venerol, Kiel, Germany
Emmanouil Dermitzakis - University of Geneva
Stephen B. Montgomery - University of Geneva
Holger Prokisch - Tech Univ Munich, Inst Human Genet, Munich, Germany
Katharina Heim - Helmholtz Zentrum München
Anna-Liisa Hartikainen - University of Oulu
Anneli Pouta - University of Oulu
Juha Pekkanen - Natl Inst Hlth & Welf THL, Kuopio, Finland
Alexandra I. F. Blakemore - University of London
Jessica L. Buxton - University of London
Marika Kaakinen - University of Oulu
David L. Duffy - College Station Medical Center
Pamela A. Madden - Supreme Council Of Health
Andrew C. Heath - Supreme Council Of Health
Grant W. Montgomery - College Station Medical Center
Philip J. Thompson - Lung Institute
Melanie C. Matheson - University of Melbourne
Peter Le Souef - Supreme Council Of Health
Beate St Pourcain
George Davey Smith - University of Bristol
John Henderson
John P. Kemp - University of Bristol
Nicholas J. Timpson - University of Bristol
Panos Deloukas - Wellcome Sanger Institute
Susan M. Ring
H-Erich Wichmann - Helmholtz Zentrum München
Martina Mueller-Nurasyid - Helmholtz Zentrum München
Natalija Novak - University of Bonn
Norman Klopp - Helmholtz Zentrum München
Elke Rodriguez - Univ Hosp Schleswig Holstein, Dept Dermatol Allergol & Venerol, Kiel, Germany
Wendy McArdle - University of Bristol
Allan Linneberg - Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Copenhagen, Denmark
Torkil Menne - University of Copenhagen
Ellen A. Nohr - Aarhus University
Albert Hofman - Erasmus MC
Andre G. Uitterlinden - Erasmus MC
Cornelia M. van Duijin - Erasmus MC
Fernando Rivadeneira - Erasmus MC
Johan C. de Jongste - Erasmus MC
Ralf J. P. van der Valk - Erasmus MC
Matthias Wjst - Helmholtz Zentrum München
Rain Jogi - Tartu Univ Hosp, Lung Clin, Tartu, Estonia
Frank Geller - Veterinary Biological and Research Institute
Heather A. Boyd - Veterinary Biological and Research Institute
Jeffrey C. Murray - University of Iowa
Cecilia Kim - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
Frank Mentch - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
Michael March - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
Massimo Mangino - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Tim D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Veronique Bataille - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Craig E. Pennell - University of Western Australia
Patrick G. Holt - University of Western Australia
Peter Sly - University of Queensland
Carla M. T. Tiesler - Helmholtz Zentrum München
Elisabeth Thiering - Helmholtz Zentrum München
Thomas Illig - Helmholtz Zentrum München
Medea Imboden - Swiss Tropical and Public Health Institute
Wenche Nystad - Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway
Angela Simpson - Natl Hlth Serv Fdn Trust, Univ Manchester, Univ S Manchester Hosp, Manchester Acad Hlth Sci Ctr,NIHR,Translat Res Fa, Manchester, Lancs, England
Jouke-Jan Hottenga - University of Amsterdam
Dirkje Postma - University of Groningen
Gerard H. Koppelman - University of Groningen
Henriette A. Smit - College Station Medical Center
Cilla Soderhall - Karolinska Institutet
Bo Chawes - University of Copenhagen
Eskil Kreiner-Moller - University of Copenhagen
Hans Bisgaard - University of Copenhagen
Erik Melen - Karolinska Institutet
Dorret I. Boomsma - University of Amsterdam
Adnan Custovic - Natl Hlth Serv Fdn Trust, Univ Manchester, Univ S Manchester Hosp, Manchester Acad Hlth Sci Ctr,NIHR,Translat Res Fa, Manchester, Lancs, England
Bo Jacobsson - Norwegian Inst Publ Hlth, Div Epidemiol, Dept Genes & Environm, Oslo, Norway
Nicole M. Probst-Hensch - Swiss Tropical and Public Health Institute
Lyle J. Palmer - University of Toronto
Daniel Glass - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Hakon Hakonarson - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
Mads Melbye - Veterinary Biological and Research Institute
Deborah L. Jarvis
Vincent W. V. Jaddoe - Erasmus MC
Christian Gieger - Helmholtz Zentrum München
David P. Strachan - University of London
Nicholas G. Martin - College Station Medical Center
Marjo-Riitta Jarvelin - University of London
Joachim Heinrich - Helmholtz Zentrum München
David M. Evans - University of Bristol
Stephan Weidinger - Univ Hosp Schleswig Holstein, Dept Dermatol Allergol & Venerol, Kiel, Germany
Australian Asthma Genetics Consort
Publication Details: Nature genetics, Vol.44(2), pp.187-192
Publisher: Springer Nature
Number of pages: 6
Grant note: R01DA012854 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission K05AA017688 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) 068545; 092731; 084762; 076467 / Wellcome Trust; European Commission 08/0003775 / Diabetes UK G0801056B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission G0800582; G9815508(74882); G0401540; G0800582(86758); G0601361(80219); G9815508; G0601361 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission R16-2007-1694 / Lundbeck Foundation; Lundbeckfonden G0800582 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) R01 DA012854 / NIDA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) K05 AA017688 / NIAAA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA)
Identifiers: 9938858208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article