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 Bønnelykke; 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; Allan Linneberg; Torkil Menné; Bo Chawes; Eskil Kreiner-Møller; Hans Bisgaard; Australian Asthma Genetics Consortium (AAGC)

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 Bønnelykke, 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 KerkhofAnnika 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, Allan Linneberg, Torkil Menné, Bo Chawes, Eskil Kreiner-Møller, Hans Bisgaard, Australian Asthma Genetics Consortium (AAGC)

Allergi, Hud- og Kønssygdomme

298 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	44
Udgave nummer	2
Sider (fra-til)	187-192
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.1017
Status	Udgivet - 25 dec. 2011

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10.1038/ng.1017

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Paternoster, L., Standl, M., Chen, C.-M., Ramasamy, A., Bønnelykke, 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., ... Australian Asthma Genetics Consortium (AAGC) (2011). 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

Paternoster, L, Standl, M, Chen, C-M, Ramasamy, A, Bønnelykke, 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, A-L, 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, Linneberg, A, Menné, T, Chawes, B, Kreiner-Møller, E, Bisgaard, H & Australian Asthma Genetics Consortium (AAGC) 2011, 'Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis', Nature Genetics, bind 44, nr. 2, s. 187-192. https://doi.org/10.1038/ng.1017

@article{3bfd85b7d4e3477085c8124b25030c58,

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 Pourcain, {Beate St} and Smith, {George Davey} and John Henderson and Kemp, {John P} and Allan Linneberg and Torkil Menn{\'e} and Bo Chawes and Eskil Kreiner-M{\o}ller and Hans Bisgaard and {Australian Asthma Genetics Consortium (AAGC)}",

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doi = "10.1038/ng.1017",

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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 - Pourcain, Beate St

AU - Smith, George Davey

AU - Henderson, John

AU - Kemp, John P

AU - Linneberg, Allan

AU - Menné, Torkil

AU - Chawes, Bo

AU - Kreiner-Møller, Eskil

AU - Bisgaard, Hans

AU - Australian Asthma Genetics Consortium (AAGC)

PY - 2011/12/25

Y1 - 2011/12/25

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.

U2 - 10.1038/ng.1017

DO - 10.1038/ng.1017

M3 - Journal article

C2 - 22197932

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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