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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.

SUBMITTER: Paternoster L 

PROVIDER: S-EPMC4753676 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Paternoster Lavinia L   Standl Marie M   Waage Johannes J   Baurecht Hansjörg H   Hotze Melanie M   Strachan David P DP   Curtin John A JA   Bønnelykke Klaus K   Tian Chao C   Takahashi Atsushi A   Esparza-Gordillo Jorge J   Alves Alexessander Couto AC   Thyssen Jacob P JP   den Dekker Herman T HT   Ferreira Manuel A MA   Altmaier Elisabeth E   Sleiman Patrick Ma PM   Xiao Feng Li FL   Gonzalez Juan R JR   Marenholz Ingo I   Kalb Birgit B   Yanes Maria Pino MP   Xu Cheng-Jian CJ   Carstensen Lisbeth L   Groen-Blokhuis Maria M MM   Venturini Cristina C   Pennell Craig E CE   Barton Sheila J SJ   Levin Albert M AM   Curjuric Ivan I   Bustamante Mariona M   Kreiner-Møller Eskil E   Lockett Gabrielle A GA   Lockett Gabrielle A GA   Bacelis Jonas J   Bacelis Jonas J   Bunyavanich Supinda S   Myers Rachel A RA   Matanovic Anja A   Kumar Ashish A   Tung Joyce Y JY   Hirota Tomomitsu T   Kubo Michiaki M   McArdle Wendy L WL   Henderson A J AJ   Kemp John P JP   Zheng Jie J   Smith George Davey GD   Rüschendorf Franz F   Bauerfeind Anja A   Lee-Kirsch Min Ae MA   Arnold Andreas A   Homuth Georg G   Schmidt Carsten O CO   Mangold Elisabeth E   Cichon Sven S   Keil Thomas T   Rodríguez Elke E   Peters Annette A   Peters Annette A   Franke Andre A   Lieb Wolfgang W   Novak Natalija N   Fölster-Holst Regina R   Horikoshi Momoko M   Pekkanen Juha J   Sebert Sylvain S   Husemoen Lise L LL   Grarup Niels N   de Jongste Johan C JC   Rivadeneira Fernando F   Hofman Albert A   Jaddoe Vincent Wv VW   Pasmans Suzanne Gma SG   Elbert Niels J NJ   Uitterlinden André G AG   Marks Guy B GB   Thompson Philip J PJ   Matheson Melanie C MC   Robertson Colin F CF   Ried Janina S JS   Li Jin J   Zuo Xian Bo XB   Zheng Xiao Dong XD   Yin Xian Yong XY   Sun Liang Dan LD   McAleer Maeve A MA   O'Regan Grainne M GM   Fahy Caoimhe Mr CM   Campbell Linda E LE   Macek Milan M   Kurek Michael M   Hu Donglei D   Eng Celeste C   Postma Dirkje S DS   Feenstra Bjarke B   Geller Frank F   Hottenga Jouke Jan JJ   Middeldorp Christel M CM   Hysi Pirro P   Bataille Veronique V   Spector Tim T   Tiesler Carla Mt CM   Thiering Elisabeth E   Pahukasahasram Badri B   Yang James J JJ   Imboden Medea M   Huntsman Scott S   Vilor-Tejedor Natàlia N   Relton Caroline L CL   Myhre Ronny R   Nystad Wenche W   Custovic Adnan A   Weiss Scott T ST   Meyers Deborah A DA   Söderhäll Cilla C   Melén Erik E   Ober Carole C   Raby Benjamin A BA   Simpson Angela A   Jacobsson Bo B   Holloway John W JW   Bisgaard Hans H   Sunyer Jordi J   Hensch Nicole M Probst NMP   Williams L Keoki LK   Godfrey Keith M KM   Wang Carol A CA   Boomsma Dorret I DI   Melbye Mads M   Koppelman Gerard H GH   Jarvis Deborah D   McLean Wh Irwin WI   Irvine Alan D AD   Zhang Xue Jun XJ   Hakonarson Hakon H   Gieger Christian C   Burchard Esteban G EG   Martin Nicholas G NG   Duijts Liesbeth L   Linneberg Allan A   Jarvelin Marjo-Riitta MR   Noethen Markus M MM   Lau Susanne S   Hübner Norbert N   Lee Young-Ae YA   Tamari Mayumi M   Hinds David A DA   Glass Daniel D   Brown Sara J SJ   Heinrich Joachim J   Evans David M DM   Weidinger Stephan S  

Nature genetics 20151019 12


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, br  ...[more]

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