Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.
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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DOI：
10.1038/ng.3424
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发表时间：
2015-12
期刊：
影响因子：
30.8
通讯作者：
Weidinger S
中科院分区：
文献类型：
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作者：
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 PM;Xiao FL;Gonzalez JR;Marenholz I;Kalb B;Yanes MP;Xu CJ;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;Rüschendorf F;Bauerfeind A;Lee-Kirsch MA;Arnold A;Homuth G;Schmidt CO;Mangold E;Cichon S;Keil T;Rodríguez E;Peters A;Franke A;Lieb W;Novak N;Fölster-Holst R;Horikoshi M;Pekkanen J;Sebert S;Husemoen LL;Grarup N;de Jongste JC;Rivadeneira F;Hofman A;Jaddoe VW;Pasmans SG;Elbert NJ;Uitterlinden AG;Marks GB;Thompson PJ;Matheson MC;Robertson CF;Australian Asthma Genetics Consortium (AAGC);Ried JS;Li J;Zuo XB;Zheng XD;Yin XY;Sun LD;McAleer MA;O'Regan GM;Fahy CM;Campbell LE;Macek M;Kurek M;Hu D;Eng C;Postma DS;Feenstra B;Geller F;Hottenga JJ;Middeldorp CM;Hysi P;Bataille V;Spector T;Tiesler CM;Thiering E;Pahukasahasram B;Yang JJ;Imboden M;Huntsman S;Vilor-Tejedor N;Relton CL;Myhre R;Nystad W;Custovic A;Weiss ST;Meyers DA;Söderhäll C;Melén E;Ober C;Raby BA;Simpson A;Jacobsson B;Holloway JW;Bisgaard H;Sunyer J;Hensch NMP;Williams LK;Godfrey KM;Wang CA;Boomsma DI;Melbye M;Koppelman GH;Jarvis D;McLean WI;Irvine AD;Zhang XJ;Hakonarson H;Gieger C;Burchard EG;Martin NG;Duijts L;Linneberg A;Jarvelin MR;Noethen MM;Lau S;Hübner N;Lee YA;Tamari M;Hinds DA;Glass D;Brown SJ;Heinrich J;Evans DM;Weidinger S
遗传关联研究已经确定了21个与特应性皮炎风险相关的基因位点，主要存在于欧洲血统人群中。为了进一步确定这种常见复杂皮肤病的易感位点，我们对来自欧洲、非洲、日本和拉丁裔人群的21399例病例和95464例对照人群的1500万个遗传变异进行了荟萃分析，随后对来自18项研究的32059例病例和228628例对照进行了重复分析。我们确定了10个新的风险位点，使已知的特应性皮炎风险位点总数达到31个（其中4个具有新的次要信号）。值得注意的是，这些新的基因座包括了调节先天宿主防御和t细胞功能的候选基因，强调了（自身）免疫机制在特应性皮炎发病机制中的重要贡献。
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 10 novel risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with novel secondary signals at 4 of these). Notably, the new loci include candidate genes with roles in regulation of innate host defenses and T-cell function, underscoring the important contribution of (auto-)immune mechanisms to atopic dermatitis pathogenesis.