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

Title: Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
Authors: Paternoster, L
Standl, M
Chen, CM
Ramasamy, A
Bonnelykke, K
Duijts, L
Ferreira, MA
Alves, AC
Thyssen, JP
Albrecht, E
Baurecht, H
Feenstra, B
Sleiman, PM
Hysi, P
Warrington, NM
Curjuric, I
Myhre, R
Curtin, JA
Groen-Blokhuis, MM
Kerkhof, M
Saaf, A
Franke, A
Ellinghaus, D
Folster-Holst, R
Dermitzakis, E
Montgomery, SB
Prokisch, H
Heim, K
Hartikainen, AL
Pouta, A
Pekkanen, J
Blakemore, AI
Buxton, JL
Kaakinen, M
Duffy, DL
Madden, PA
Heath, AC
Montgomery, GW
Thompson, PJ
Matheson, MC
Le Souef, P
St Pourcain, B
Smith, GD
Henderson, J
Kemp, JP
Timpson, NJ
Deloukas, P
Ring, SM
Wichmann, HE
Muller-Nurasyid, M
Novak, N
Klopp, N
Rodriguez, E
McArdle, W
Linneberg, A
Menne, T
Nohr, EA
Hofman, A
Uitterlinden, AG
Van Duijn, CM
Rivadeneira, F
De Jongste, JC
Van der Valk, RJ
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, CM
Thiering, E
Illig, T
Imboden, M
Nystad, W
Simpson, A
Hottenga, JJ
Postma, D
Koppelman, GH
Smit, HA
Soderhall, C
Chawes, B
Kreiner-Moller, E
Bisgaard, H
Melen, E
Boomsma, DI
Custovic, A
Jacobsson, B
Probst-Hensch, NM
Palmer, LJ
Glass, D
Hakonarson, H
Melbye, M
Item Type: Journal Article
Issue Date: 25-Dec-2011
Date of Acceptance: 1-Nov-2011
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/Funder: Medical Research Council (MRC)
Funder's Grant Number: G0801056B
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Cell Differentiation
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 5
DNA-Binding Proteins
Dermatitis, Atopic
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Intermediate Filament Proteins
Polymorphism, Single Nucleotide
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
Appears in Collections:Infectious Disease Epidemiology
National Heart and Lung Institute
Department of Medicine
Epidemiology, Public Health and Primary Care

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