Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
Author(s)
Type
Journal Article
Date Issued
2011-12-25
Date Acceptance
2011-11-01
ISSN
1546-1718
Publisher
Nature Publishing Group
Start Page
187
End Page
192
Journal / Book Title
Nature Genetics
Volume
44
Copyright Statement
© 2011, Rights Managed by Nature Publishing Group
Sponsor
Medical Research Council (MRC)
Grant Number
G0801056B
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENETICS & HEREDITY
CELLULAR MOTILITY
EXPRESSION
PSORIASIS
DISEASE
DIFFERENTIATION
VARIANTS
ASTHMA
SPERMATOGENESIS
MECHANISMS
FILAGGRIN
Cell Differentiation
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 5
Cytokines
DNA-Binding Proteins
Dermatitis, Atopic
Epidermis
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Intermediate Filament Proteins
Kinesin
Male
Polymorphism, Single Nucleotide
Risk
Transcription Factors
Australian Asthma Genetics Consortium (AAGC)
Genetics of Overweight Young Adults (GOYA) Consortium
EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium
Cell Differentiation/genetics Chromosomes, Human, Pair 11/genetics Chromosomes, Human, Pair 20/genetics Chromosomes, Human, Pair 5 Cytokines/genetics DNA-Binding Proteins/genetics Dermatitis, Atopic/*genetics/immunology Epidermis/immunology Female *Genetic Loci Genetic Predisposition to Disease *Genome-Wide Association Study Humans Intermediate Filament Proteins/genetics Kinesin/genetics Male Polymorphism, Single Nucleotide Risk Transcription Factors/genetics
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Notes
Paternoster, Lavinia Standl, Marie Chen, Chih-Mei Ramasamy, Adaikalavan Bonnelykke, Klaus Duijts, Liesbeth Ferreira, Manuel A Alves, Alexessander Couto Thyssen, Jacob P Albrecht, Eva Baurecht, Hansjorg Feenstra, Bjarke Sleiman, Patrick M A Hysi, Pirro Warrington, Nicole M Curjuric, Ivan Myhre, Ronny Curtin, John A Groen-Blokhuis, Maria M Kerkhof, Marjan Saaf, Annika Franke, Andre Ellinghaus, David Folster-Holst, Regina Dermitzakis, Emmanouil Montgomery, Stephen B Prokisch, Holger Heim, Katharina Hartikainen, Anna-Liisa Pouta, Anneli Pekkanen, Juha Blakemore, Alexandra I F Buxton, Jessica L Kaakinen, Marika Duffy, David L Madden, Pamela A Heath, Andrew C Montgomery, Grant W Thompson, Philip J Matheson, Melanie C Le Souef, Peter Australian Asthma Genetics Consortium (AAGC) St Pourcain, Beate Smith, George Davey Henderson, John Kemp, John P Timpson, Nicholas J Deloukas, Panos Ring, Susan M Wichmann, H-Erich Muller-Nurasyid, Martina Novak, Natalija Klopp, Norman Rodriguez, Elke McArdle, Wendy Linneberg, Allan Menne, Torkil Nohr, Ellen A Hofman, Albert Uitterlinden, Andre G van Duijn, Cornelia M Rivadeneira, Fernando de Jongste, Johan C van der Valk, Ralf J P Wjst, Matthias Jogi, Rain Geller, Frank Boyd, Heather A Murray, Jeffrey C Kim, Cecilia Mentch, Frank March, Michael Mangino, Massimo Spector, Tim D Bataille, Veronique Pennell, Craig E Holt, Patrick G Sly, Peter Tiesler, Carla M T Thiering, Elisabeth Illig, Thomas Imboden, Medea Nystad, Wenche Simpson, Angela Hottenga, Jouke-Jan Postma, Dirkje Koppelman, Gerard H Smit, Henriette A Soderhall, Cilla Chawes, Bo Kreiner-Moller, Eskil Bisgaard, Hans Melen, Erik Boomsma, Dorret I Custovic, Adnan Jacobsson, Bo Probst-Hensch, Nicole M Palmer, Lyle J Glass, Daniel Hakonarson, Hakon Melbye, Mads Jarvis, Deborah L Jaddoe, Vincent W V Gieger, Christian Genetics of Overweight Young Adults (GOYA) Consortium Strachan, David P Martin, Nicholas G Jarvelin, Marjo-Riitta Heinrich, Joachim Evans, David M Weidinger, Stephan EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium 068545/Wellcome Trust/United Kingdom 076467/Wellcome Trust/United Kingdom 084762/Wellcome Trust/United Kingdom 092731/Wellcome Trust/United Kingdom G0601361/Medical Research Council/United Kingdom G0601361(80219)/Medical Research Council/United Kingdom G0800582/Medical Research Council/United Kingdom G0800582(86758)/Medical Research Council/United Kingdom G9815508/Medical Research Council/United Kingdom G9815508(74882)/Medical Research Council/United Kingdom K05 AA017688/AA/NIAAA NIH HHS/United States R01 DA012854-10/DA/NIDA NIH HHS/United States Meta-Analysis United States Nature genetics Nat Genet. 2011 Dec 25;44(2):187-92. doi: 10.1038/ng.1017. 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.
Publication Status
Published