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Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922991/ https://www.ncbi.nlm.nih.gov/pubmed/36793728 http://dx.doi.org/10.3389/fimmu.2023.1080071 |
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author | Recto, Kathryn A. Huan, Tianxiao Lee, Dong Heon Lee, Gha Young Gereige, Jessica Yao, Chen Hwang, Shih-Jen Joehanes, Roby Kelly, Rachel S. Lasky-Su, Jessica O’Connor, George Levy, Daniel |
author_facet | Recto, Kathryn A. Huan, Tianxiao Lee, Dong Heon Lee, Gha Young Gereige, Jessica Yao, Chen Hwang, Shih-Jen Joehanes, Roby Kelly, Rachel S. Lasky-Su, Jessica O’Connor, George Levy, Daniel |
author_sort | Recto, Kathryn A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9922991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99229912023-02-14 Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases Recto, Kathryn A. Huan, Tianxiao Lee, Dong Heon Lee, Gha Young Gereige, Jessica Yao, Chen Hwang, Shih-Jen Joehanes, Roby Kelly, Rachel S. Lasky-Su, Jessica O’Connor, George Levy, Daniel Front Immunol Immunology 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. Frontiers Media S.A. 2023-01-30 /pmc/articles/PMC9922991/ /pubmed/36793728 http://dx.doi.org/10.3389/fimmu.2023.1080071 Text en Copyright © 2023 Recto, Huan, Lee, Lee, Gereige, Yao, Hwang, Joehanes, Kelly, Lasky-Su, O’Connor and Levy https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Recto, Kathryn A. Huan, Tianxiao Lee, Dong Heon Lee, Gha Young Gereige, Jessica Yao, Chen Hwang, Shih-Jen Joehanes, Roby Kelly, Rachel S. Lasky-Su, Jessica O’Connor, George Levy, Daniel Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases |
title | Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases |
title_full | Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases |
title_fullStr | Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases |
title_full_unstemmed | Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases |
title_short | Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases |
title_sort | transcriptome-wide association study of circulating ige levels identifies novel targets for asthma and allergic diseases |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922991/ https://www.ncbi.nlm.nih.gov/pubmed/36793728 http://dx.doi.org/10.3389/fimmu.2023.1080071 |
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