Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases.
Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases.
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循环IgE水平的全转录组结合研究确定了哮喘和过敏性疾病的新靶标。
DOI：
10.3389/fimmu.2023.1080071
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发表时间：
2023
影响因子：
7.3
通讯作者：
Levy, Daniel
中科院分区：
文献类型：
--
作者：
Recto, Kathryn A. A.;Huan, Tianxiao;Lee, Dong Heon;Lee, Gha Young;Gereige, Jessica;Yao, Chen;Hwang, Shih-Jen;Joehanes, Roby;Kelly, Rachel S. S.;Lasky-Su, Jessica;O'Connor, George;Levy, Daniel
测定循环免疫球蛋白E（IgE）浓度有助于哮喘及过敏性疾病的诊断和治疗。鉴定与IgE相关的基因表达特征可能阐明IgE调节的新途径。为此，我们进行了一项发现全转录组关联研究，以确定与全血来源RNA中循环IgE水平相关的差异表达基因，这些RNA来自Frachial Heart研究中的5，345名参与者的17，873个mRNA基因水平转录本。我们以<0.05的错误发现率鉴定了216个显著的转录本。我们使用两项独立外部研究的荟萃分析进行复制：儿童哮喘管理计划（n=610）和哥斯达黎加哮喘遗传流行病学研究（n=326）;然后我们逆转了发现和复制队列，发现了59个双向复制的重要基因。基因本体分析显示，这些基因中的许多涉及免疫功能途径，包括防御反应，炎症反应和细胞因子的产生。孟德尔随机化（MR）分析揭示了四个基因（CLC、CCDC 21、S100 A13和GCNT 1）作为IgE水平的致病性（p<0.05）调节因子。GCNT 1（β =1.5，p=0.01）--这是与哮喘和过敏性疾病相关的表达的MR分析的最高结果--在调节T辅助1型细胞归巢、淋巴细胞运输和B细胞分化中起作用。我们的研究结果建立在IgE调节的先验知识基础上，并提供了对潜在分子机制的更深入理解。我们发现的IgE相关基因，特别是那些涉及MR分析，可以探索作为有前途的治疗哮喘和IgE相关疾病的目标。
Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study to identify differentially expressed genes associated with circulating IgE levels in whole-blood derived RNA from 5,345 participants in the Framingham Heart Study across 17,873 mRNA gene-level transcripts. We identified 216 significant transcripts at a false discovery rate <0.05. We conducted replication using the meta-analysis of two independent external studies: the Childhood Asthma Management Program (n=610) and the Genetic Epidemiology of Asthma in Costa Rica Study (n=326); we then reversed the discovery and replication cohorts, which revealed 59 significant genes that replicated in both directions. Gene ontology analysis revealed that many of these genes were implicated in immune function pathways, including defense response, inflammatory response, and cytokine production. Mendelian randomization (MR) analysis revealed four genes (CLC, CCDC21, S100A13, and GCNT1) as putatively causal (p<0.05) regulators of IgE levels. GCNT1 (beta=1.5, p=0.01)—which is a top result in the MR analysis of expression in relation to asthma and allergic diseases—plays a role in regulating T helper type 1 cell homing, lymphocyte trafficking, and B cell differentiation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms. The IgE-associated genes that we identified—particularly those implicated in MR analysis—can be explored as promising therapeutic targets for asthma and IgE-related diseases.
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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
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：
8
作者：
Fonseca, Kaori L.;Maceiras, Ana Raquel;Saraiva, Margarida
通讯作者：
Saraiva, Margarida
影响因子：
9
作者：
Mukai, Kaori;Tsai, Mindy;Starkl, Philipp;Marichal, Thomas;Galli, Stephen J.
通讯作者：
Galli, Stephen J.
针对 IgE 介导的过敏性疾病的抗 IgE 疗法：从中和 IgE 抗体到消除 IgE( ) B 细胞
影响因子：
4.4
作者：
Hu J;Chen J;Ye L;Cai Z;Sun J;Ji K
通讯作者：
Ji K