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

Lavinia Paternoster; Marie Standl; Australian Asthma Genetics Consortium (AAGC); The Genetics of Overweight Young Adults (GOYA) Consortium

doi:10.1038/ng.1017

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

Lavinia Paternoster, Marie Standl, Australian Asthma Genetics Consortium (AAGC), The Genetics of Overweight Young Adults (GOYA) Consortium

Research output: Contribution to journal › Article (Academic Journal)

206 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
Early online date	25 Dec 2011
DOIs	https://doi.org/10.1038/ng.1017
Publication status	Published - Feb 2012

Access to Document

10.1038/ng.1017

http://www.nature.com/ng/journal/v44/n2/full/ng.1017.html

Fingerprint Dive into the research topics of 'Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis'. Together they form a unique fingerprint.

Projects

3 Finished

B603 THE EFFECT OF COMMON DISEASE ASSOCIATED GENETIC VARIANTS ON TRANSCRIPTOMIC AND EARLY LIFE PHENOTYPES

Evans, D.

1/09/08 → 1/09/11

Project: Research

THE NATURAL HISTORY OF ASTHMA AND WHEEZING ILLNESSES FROM BIRTH TO ADOLESCENCE: DETERMINANTS OF THE REMISSION OF ASTHMA

Henderson, A. J. W.

1/10/06 → 1/10/10

Project: Research

EXTENSION OF RD1321 VIA IOP.

Golding, J.

1/02/01 → 1/02/06

Project: Research

Cite this

Paternoster, L., Standl, M., Australian Asthma Genetics Consortium (AAGC), & The Genetics of Overweight Young Adults (GOYA) Consortium (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{e7f2cf930bf14a1783e4155a431d50bb,

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 Chih-Mei Chen and Adaikalavan Ramasamy and Klaus B{\o}nnelykke 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 Anna-Liisa Hartikainen 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 {St Pourcain}, Beate and Smith, {George Davey} and John Henderson and Kemp, {John P} and Timpson, {Nicholas J} and Panos Deloukas and Ring, {Susan M} and Wendy McArdle and Palmer, {Lyle J} and {Australian Asthma Genetics Consortium (AAGC)} and {The Genetics of Overweight Young Adults (GOYA) Consortium}",

year = "2012",

month = feb,

doi = "10.1038/ng.1017",

language = "English",

volume = "44",

pages = "187--192",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

number = "2",

}

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. / Paternoster, Lavinia; Standl, Marie; Australian Asthma Genetics Consortium (AAGC); The Genetics of Overweight Young Adults (GOYA) Consortium.

In: Nature Genetics, Vol. 44, No. 2, 02.2012, p. 187-192.

Research output: Contribution to journal › Article (Academic Journal)

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 - Bønnelykke, 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 - St Pourcain, Beate

AU - Smith, George Davey

AU - Henderson, John

AU - Kemp, John P

AU - Timpson, Nicholas J

AU - Deloukas, Panos

AU - Ring, Susan M

AU - McArdle, Wendy

AU - Palmer, Lyle J

AU - Australian Asthma Genetics Consortium (AAGC)

AU - The Genetics of Overweight Young Adults (GOYA) Consortium

PY - 2012/2

Y1 - 2012/2

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.

U2 - 10.1038/ng.1017

DO - 10.1038/ng.1017

M3 - Article (Academic Journal)

C2 - 22197932

VL - 44

SP - 187

EP - 192

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -