A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.
A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.
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DOI：
10.1183/13993003.02693-2020
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Celedón JC
中科院分区：
文献类型：
--
作者：
Yan Q;Forno E;Herrera-Luis E;Pino-Yanes M;Qi C;Rios R;Han YY;Kim S;Oh S;Acosta-Pérez E;Zhang R;Hu D;Eng C;Huntsman S;Avila L;Boutaoui N;Cloutier MM;Soto-Quiros ME;Xu CJ;Weiss ST;Lasky-Su J;Kiedrowski MR;Figueiredo C;Bomberger J;Barreto ML;Canino G;Chen W;Koppelman GH;Burchard EG;Celedón JC
严重哮喘急性发作是儿童缺课和医疗费用的主要原因，特别是那些高危种族/民族群体。为了确定拉丁美洲儿童和青少年严重哮喘急性发作的易感基因，我们对4个独立队列中的4，010名拉丁美洲青少年哮喘患者进行了全基因组关联研究（GWAS）的荟萃分析，其中包括1，693名波多黎各人，1，019名哥斯达黎加人，640名墨西哥人，256名巴西人和402名其他拉丁美洲亚组成员。然后，我们进行了甲基化数量性状基因座（mQTL），表达数量性状基因座（eQTL）和表达数量性状甲基化（eQTM）分析，以评估荟萃分析中最高的SNP是否与波多黎各和荷兰儿童和青少年不同队列中鼻（气道）上皮的DNA甲基化和基因表达相关。在GWAS的荟萃分析中，FLJ 22447（rs 2253681）中的SNP与重度哮喘急性发作的几率增加1.55显著相关（95%置信区间= 1.34至1.79，P=6.3×10−9）。该SNP与FLJ 22447位点的CpG位点（cg 25024579）的DNA甲基化显著相关，而这又与波多黎各儿童和青少年鼻气道上皮中KCNJ 2-AS 1表达增加相关（β=0.10，P=2.18 x 10−7）。SNP rs 2253681与FLJ 22447顺式CpG的DNA甲基化和拉丁裔青年的严重哮喘急性发作显著相关。这可能部分解释了气道上皮细胞表达的基因的变化，最近牵连在特应性哮喘在波多黎各儿童和青少年（KCNJ 2-AS 1）。
Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4,010 Latino youth with asthma in four independent cohorts, including 1,693 Puerto Ricans, 1,019 Costa Ricans, 640 Mexicans, 256 Brazilians, and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus (mQTL), expression quantitative trait locus (eQTL), and expression quantitative trait methylation (eQTM) analyses to assess whether the top SNP in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents. In the meta-analysis of GWAS, a SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbations (95% confidence interval= 1.34 to 1.79, P=6.3×10−9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, P=2.18 x 10−7). SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1).
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影响因子：
30.8
作者：
Demenais F;Margaritte-Jeannin P;Barnes KC;Cookson WOC;Altmüller J;Ang W;Barr RG;Beaty TH;Becker AB;Beilby J;Bisgaard H;Bjornsdottir US;Bleecker E;Bønnelykke K;Boomsma DI;Bouzigon E;Brightling CE;Brossard M;Brusselle GG;Burchard E;Burkart KM;Bush A;Chan-Yeung M;Chung KF;Couto Alves A;Curtin JA;Custovic A;Daley D;de Jongste JC;Del-Rio-Navarro BE;Donohue KM;Duijts L;Eng C;Eriksson JG;Farrall M;Fedorova Y;Feenstra B;Ferreira MA;Australian Asthma Genetics Consortium (AAGC) collaborators;Freidin MB;Gajdos Z;Gauderman J;Gehring U;Geller F;Genuneit J;Gharib SA;Gilliland F;Granell R;Graves PE;Gudbjartsson DF;Haahtela T;Heckbert SR;Heederik D;Heinrich J;Heliövaara M;Henderson J;Himes BE;Hirose H;Hirschhorn JN;Hofman A;Holt P;Hottenga J;Hudson TJ;Hui J;Imboden M;Ivanov V;Jaddoe VWV;James A;Janson C;Jarvelin MR;Jarvis D;Jones G;Jonsdottir I;Jousilahti P;Kabesch M;Kähönen M;Kantor DB;Karunas AS;Khusnutdinova E;Koppelman GH;Kozyrskyj AL;Kreiner E;Kubo M;Kumar R;Kumar A;Kuokkanen M;Lahousse L;Laitinen T;Laprise C;Lathrop M;Lau S;Lee YA;Lehtimäki T;Letort S;Levin AM;Li G;Liang L;Loehr LR;London SJ;Loth DW;Manichaikul A;Marenholz I;Martinez FJ;Matheson MC;Mathias RA;Matsumoto K;Mbarek H;McArdle WL;Melbye M;Melén E;Meyers D;Michel S;Mohamdi H;Musk AW;Myers RA;Nieuwenhuis MAE;Noguchi E;O'Connor GT;Ogorodova LM;Palmer CD;Palotie A;Park JE;Pennell CE;Pershagen G;Polonikov A;Postma DS;Probst-Hensch N;Puzyrev VP;Raby BA;Raitakari OT;Ramasamy A;Rich SS;Robertson CF;Romieu I;Salam MT;Salomaa V;Schlünssen V;Scott R;Selivanova PA;Sigsgaard T;Simpson A;Siroux V;Smith LJ;Solodilova M;Standl M;Stefansson K;Strachan DP;Stricker BH;Takahashi A;Thompson PJ;Thorleifsson G;Thorsteinsdottir U;Tiesler CMT;Torgerson DG;Tsunoda T;Uitterlinden AG;van der Valk RJP;Vaysse A;Vedantam S;von Berg A;von Mutius E;Vonk JM;Waage J;Wareham NJ;Weiss ST;White WB;Wickman M;Widén E;Willemsen G;Williams LK;Wouters IM;Yang JJ;Zhao JH;Moffatt MF;Ober C;Nicolae DL
通讯作者：
Nicolae DL
DOI：
10.1152/ajplung.00510.2016
发表时间：
2017-07-01
影响因子：
4.9
作者：
Liu, Tian;Liu, Yahui;Dong, Liang
通讯作者：
Dong, Liang
影响因子：
30.8
作者：
Bonnelykke, Klaus;Sleiman, Patrick;Bisgaard, Hans
通讯作者：
Bisgaard, Hans
影响因子：
14.2
作者：
Hunninghake, Gary M.;Soto-Quiros, Manuel E.;Celedon, Juan C.
通讯作者：
Celedon, Juan C.
影响因子：
4.3
作者：
de Leeuw CA;Mooij JM;Heskes T;Posthuma D
通讯作者：
Posthuma D