Multiethnic genome-wide and HLA association study of total serum IgE level.
Multiethnic genome-wide and HLA association study of total serum IgE level.
复制标题
DOI：
10.1016/j.jaci.2021.09.011
复制
发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Barnes KC
中科院分区：
文献类型：
--
作者：
Daya M;Cox C;Acevedo N;Boorgula MP;Campbell M;Chavan S;Cho MH;David GL;Kachroo P;Lasky-Su J;Li X;McHugh CP;Qiao D;Rafaels N;Beck LA;Bleecker ER;Caraballo L;Cupples AL;Figueiredo CA;Gallo RL;Hanifin J;Hansel NN;Hata TR;Hersh CP;Knight-Madden J;Leung DYM;Guttman-Yassky E;Meyers DA;O'Connor G;Ober C;Ong PY;Ortega VE;Paller AS;Putcha N;Reed RM;Schneider LC;Silverman EK;Slifka MK;Spergel JM;Vasan RS;Viaud-Martinez KA;Watson H;Weiss ST;NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium;Ruczinski I;Beaty TH;Mathias RA;Barnes KC
血清总IgE（tIgE）是变态反应性疾病的重要中间表型。跨祖先的全基因组遗传关联研究可以确定IgE的重要决定因素。通过利用来自NHLBI精准医学跨组学（TOPMed）计划，美洲非洲血统人群哮喘联盟（CAAPA）和特应性皮肤病研究网络（ADRN）的数据，我们的目标是增加对影响整个血统和过敏性疾病谱（N= 21，901）中tIgE产生的遗传变异的理解。我们在研究、疾病和祖先群体的分层内进行了全基因组关联，并通过荟萃回归方法对归因于祖先的异质性进行了建模。我们还测试了从全基因组序列数据调用的HLA等位基因与tIgE之间的关联，评估了从基因型阵列数据调用的HLA等位基因中关联的复制。有关详细信息，请参阅本文在线知识库中的方法部分www.jacionline.org。我们确定了6个具有全基因组显著性的位点（P<5×10−9），包括4个先前报道的对tIgE具有全基因组显著性的位点，以及chr11q13.5和chr15q22.2中的新区域，这些区域也在特应性皮炎和哮喘的先前GWAS中确定。在HLA等位基因关联研究中，HLA-A*02：01与西班牙裔/拉丁裔人群中tIgE降低相关（发现P = 2×10−4，复制P = 5×10−4，发现+复制P=4×10−7），HLA-DQB 1 *03：02与西班牙裔/拉丁裔人群中tIgE降低密切相关（西班牙裔/拉丁裔发现+复制P=8×10−8）。我们进行了最大的GWAS和HLA相关性研究tIgE集中在祖先不同的人群，并发现了几个已知的tIgE和过敏性疾病基因座，在非欧洲血统的人群。已知的tIgE和过敏性疾病基因座与非欧洲血统人群相关。HLA-A*02：01和HLA-DQB 1 *03：02与tIgE水平降低相关。
Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE. By leveraging data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) and the Atopic Dermatitis Research Network (ADRN), we aim to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum (N=21,901). We performed genome-wide association within strata of study, disease, and ancestry groups, and combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data. For details, please see the Methods section in this article’s Online Repository at www.jacionline.org. We identified six loci at genome-wide significance (P<5×10−9), including four loci previously reported as genome-wide significant for tIgE, as well as new regions in chr11q13.5 and chr15q22.2, also identified in prior GWAS of atopic dermatitis and asthma. In the HLA allele association study, HLA-A*02:01 was associated with decreased tIgE (discovery P = 2×10−4, replication P = 5×10−4, discovery+replication P=4×10−7) and HLA-DQB1*03:02 was strongly associated with decreased tIgE in Hispanic/Latino ancestry populations (Hispanic/Latino discovery+replication P=8×10−8). We performed the largest GWAS and HLA association study of tIgE focused on ancestrally diverse populations and found several known tIgE and allergic disease loci that are relevant in non-European ancestry populations. Known tIgE and allergic disease loci are relevant in non-European ancestry populations. HLA-A*02:01 and HLA-DQB1*03:02 are associated with decreased levels of tIgE.
登录
查看更多内容
影响因子：
14.2
作者：
Levin, Albert M.;Mathias, Rasika A.;Huang, Lili;Roth, Lindsey A.;Daley, Denise;Myers, Rachel A.;Himes, Blanca E.;Romieu, Isabelle;Yang, Mao;Eng, Celeste;Park, Julie E.;Zoratti, Karla;Gignoux, Christopher R.;Torgerson, Dara G.;Galanter, Joshua M.;Huntsman, Scott;Nguyen, Elizabeth A.;Becker, Allan B.;Chan-Yeung, Moira;Kozyrskyj, Anita L.;Kwok, Pui-Yan;Gilliland, Frank D.;Gauderman, W. James;Bleecker, Eugene R.;Raby, Benjamin A.;Meyers, Deborah A.;London, Stephanie J.;Martinez, Fernando D.;Weiss, Scott T.;Burchard, Esteban G.;Nicolae, Dan L.;Ober, Carole;Barnes, Kathleen C.;Williams, L. Keoki
通讯作者：
Williams, L. Keoki
全基因组扫描在总血清IgE水平上鉴定出FCER1A是新的敏感性基因座。
影响因子：
4.5
作者：
Weidinger, Stephan;Gieger, Christian;Rodriguez, Elke;Baurecht, Hansjoerg;Mempel, Martin;Klopp, Norman;Gohlke, Henning;Wagenpfeil, Stefan;Ollert, Markus;Ring, Johannes;Behrendt, Heidrun;Heinrich, Joachim;Novak, Natalija;Bieber, Thomas;Kraemer, Ursula;Berdel, Dietrich;von Berg, Andrea;Bauer, Carl Peter;Herbarth, Olf;Koletzko, Sibylle;Prokisch, Holger;Mehta, Divya;Meitinger, Thomas;Depner, Martin;von Mutius, Erika;Liang, Liming;Moffatt, Miriam;Cookson, William;Kabesch, Michael;Wichmann, H. -Erich;Illig, Thomas
通讯作者：
Illig, Thomas
DOI：
10.1016/j.jaci.2011.09.029
发表时间：
2012-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Granada M;Wilk JB;Tuzova M;Strachan DP;Weidinger S;Albrecht E;Gieger C;Heinrich J;Himes BE;Hunninghake GM;Celedón JC;Weiss ST;Cruikshank WW;Farrer LA;Center DM;O'Connor GT
通讯作者：
O'Connor GT
影响因子：
2.1
作者：
Lin, Dan-Yu
通讯作者：
Lin, Dan-Yu
影响因子：
3.6
作者：
Ezell, Scott A.;Tsichlis, Philip N.
通讯作者：
Tsichlis, Philip N.