Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Lavinia Paternoster; Marie Standl; Johannes Waage; Hansjörg Baurecht; Melanie Hotze; David P Strachan; John A Curtin; Klaus Bønnelykke; Chao Tian; Atsushi Takahashi; Jorge Esparza-Gordillo; Alexessander Couto Alves; Jacob P Thyssen; Herman T den Dekker; Manuel A Ferreira; Elisabeth Altmaier; Patrick M A Sleiman; Feng Li Xiao; Juan R Gonzalez; Ingo Marenholz; Birgit Kalb; Maria Pino-Yanes; Cheng-Jian Xu; Lisbeth Carstensen; Maria M Groen-Blokhuis; Cristina Venturini; Craig E Pennell; Sheila J Barton; Albert M Levin; Ivan Curjuric; Mariona Bustamante; Eskil Kreiner-Møller; Gabrielle A Lockett; Jonas Bacelis; Supinda Bunyavanich; Rachel A Myers; Anja Matanovic; Ashish Kumar; Joyce Y Tung; Tomomitsu Hirota; Michiaki Kubo; Wendy L McArdle; A John Henderson; John P Kemp; Jie Zheng; George Davey Smith; Niels Grarup; Hans Bisgaard; Mads Melbye; Allan Linneberg; Australian Asthma Genetics Consortium (AAGC)

doi:10.1038/ng.3424

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Lavinia Paternoster, Marie Standl, Johannes Waage, Hansjörg Baurecht, Melanie Hotze, David P Strachan, John A Curtin, Klaus Bønnelykke, Chao Tian, Atsushi Takahashi, Jorge Esparza-Gordillo, Alexessander Couto Alves, Jacob P Thyssen, Herman T den Dekker, Manuel A Ferreira, Elisabeth Altmaier, Patrick M A Sleiman, Feng Li Xiao, Juan R Gonzalez, Ingo MarenholzBirgit Kalb, Maria Pino-Yanes, Cheng-Jian Xu, Lisbeth Carstensen, Maria M Groen-Blokhuis, Cristina Venturini, Craig E Pennell, Sheila J Barton, Albert M Levin, Ivan Curjuric, Mariona Bustamante, Eskil Kreiner-Møller, Gabrielle A Lockett, Jonas Bacelis, Supinda Bunyavanich, Rachel A Myers, Anja Matanovic, Ashish Kumar, Joyce Y Tung, Tomomitsu Hirota, Michiaki Kubo, Wendy L McArdle, A John Henderson, John P Kemp, Jie Zheng, George Davey Smith, Niels Grarup, Hans Bisgaard, Mads Melbye, Allan Linneberg, Australian Asthma Genetics Consortium (AAGC)

270 Citationer (Scopus)

Abstract

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	47
Udgave nummer	12
Sider (fra-til)	1449-56
Antal sider	8
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.3424
Status	Udgivet - 1 dec. 2015

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10.1038/ng.3424

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Paternoster, L., Standl, M., Waage, J., Baurecht, H., Hotze, M., Strachan, D. P., Curtin, J. A., Bønnelykke, K., Tian, C., Takahashi, A., Esparza-Gordillo, J., Alves, A. C., Thyssen, J. P., den Dekker, H. T., Ferreira, M. A., Altmaier, E., Sleiman, P. M. A., Xiao, F. L., Gonzalez, J. R., ... Australian Asthma Genetics Consortium (AAGC) (2015). Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nature Genetics, 47(12), 1449-56. https://doi.org/10.1038/ng.3424

Paternoster, L, Standl, M, Waage, J, Baurecht, H, Hotze, M, Strachan, DP, Curtin, JA, Bønnelykke, K, Tian, C, Takahashi, A, Esparza-Gordillo, J, Alves, AC, Thyssen, JP, den Dekker, HT, Ferreira, MA, Altmaier, E, Sleiman, PMA, Xiao, FL, Gonzalez, JR, Marenholz, I, Kalb, B, Pino-Yanes, M, Xu, C-J, Carstensen, L, Groen-Blokhuis, MM, Venturini, C, Pennell, CE, Barton, SJ, Levin, AM, Curjuric, I, Bustamante, M, Kreiner-Møller, E, Lockett, GA, Bacelis, J, Bunyavanich, S, Myers, RA, Matanovic, A, Kumar, A, Tung, JY, Hirota, T, Kubo, M, McArdle, WL, Henderson, AJ, Kemp, JP, Zheng, J, Smith, GD, Grarup, N, Bisgaard, H, Melbye, M , Linneberg, A & Australian Asthma Genetics Consortium (AAGC) 2015, 'Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis', Nature Genetics, bind 47, nr. 12, s. 1449-56. https://doi.org/10.1038/ng.3424

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title = "Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis",

abstract = "Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.",

author = "Lavinia Paternoster and Marie Standl and Johannes Waage and Hansj{\"o}rg Baurecht and Melanie Hotze and Strachan, {David P} and Curtin, {John A} and Klaus B{\o}nnelykke and Chao Tian and Atsushi Takahashi and Jorge Esparza-Gordillo and Alves, {Alexessander Couto} and Thyssen, {Jacob P} and {den Dekker}, {Herman T} and Ferreira, {Manuel A} and Elisabeth Altmaier and Sleiman, {Patrick M A} and Xiao, {Feng Li} and Gonzalez, {Juan R} and Ingo Marenholz and Birgit Kalb and Maria Pino-Yanes and Cheng-Jian Xu and Lisbeth Carstensen and Groen-Blokhuis, {Maria M} and Cristina Venturini and Pennell, {Craig E} and Barton, {Sheila J} and Levin, {Albert M} and Ivan Curjuric and Mariona Bustamante and Eskil Kreiner-M{\o}ller and Lockett, {Gabrielle A} and Jonas Bacelis and Supinda Bunyavanich and Myers, {Rachel A} and Anja Matanovic and Ashish Kumar and Tung, {Joyce Y} and Tomomitsu Hirota and Michiaki Kubo and McArdle, {Wendy L} and Henderson, {A John} and Kemp, {John P} and Jie Zheng and Smith, {George Davey} and Niels Grarup and Hans Bisgaard and Mads Melbye and Allan Linneberg and {Australian Asthma Genetics Consortium (AAGC)}",

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AU - Standl, Marie

AU - Waage, Johannes

AU - Baurecht, Hansjörg

AU - Hotze, Melanie

AU - Strachan, David P

AU - Curtin, John A

AU - Bønnelykke, Klaus

AU - Tian, Chao

AU - Takahashi, Atsushi

AU - Esparza-Gordillo, Jorge

AU - Alves, Alexessander Couto

AU - Thyssen, Jacob P

AU - den Dekker, Herman T

AU - Ferreira, Manuel A

AU - Altmaier, Elisabeth

AU - Sleiman, Patrick M A

AU - Xiao, Feng Li

AU - Gonzalez, Juan R

AU - Marenholz, Ingo

AU - Kalb, Birgit

AU - Pino-Yanes, Maria

AU - Xu, Cheng-Jian

AU - Carstensen, Lisbeth

AU - Groen-Blokhuis, Maria M

AU - Venturini, Cristina

AU - Pennell, Craig E

AU - Barton, Sheila J

AU - Levin, Albert M

AU - Curjuric, Ivan

AU - Bustamante, Mariona

AU - Kreiner-Møller, Eskil

AU - Lockett, Gabrielle A

AU - Bacelis, Jonas

AU - Bunyavanich, Supinda

AU - Myers, Rachel A

AU - Matanovic, Anja

AU - Kumar, Ashish

AU - Tung, Joyce Y

AU - Hirota, Tomomitsu

AU - Kubo, Michiaki

AU - McArdle, Wendy L

AU - Henderson, A John

AU - Kemp, John P

AU - Zheng, Jie

AU - Smith, George Davey

AU - Grarup, Niels

AU - Bisgaard, Hans

AU - Melbye, Mads

AU - Linneberg, Allan

AU - Australian Asthma Genetics Consortium (AAGC)

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N2 - Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

AB - Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

U2 - 10.1038/ng.3424

DO - 10.1038/ng.3424

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JO - Nature: New biology

JF - Nature: New biology

IS - 12

ER -

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

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