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Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

BACKGROUND: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. RESULT: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune...

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Autores principales: Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A. C. M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J. P. M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng-Jian, Joosten, Leo A. B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., Li, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259168/
https://www.ncbi.nlm.nih.gov/pubmed/34229738
http://dx.doi.org/10.1186/s13059-021-02413-z
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author Chu, Xiaojing
Jaeger, Martin
Beumer, Joep
Bakker, Olivier B.
Aguirre-Gamboa, Raul
Oosting, Marije
Smeekens, Sanne P.
Moorlag, Simone
Mourits, Vera P.
Koeken, Valerie A. C. M.
de Bree, Charlotte
Jansen, Trees
Mathews, Ian T.
Dao, Khoi
Najhawan, Mahan
Watrous, Jeramie D.
Joosten, Irma
Sharma, Sonia
Koenen, Hans J. P. M.
Withoff, Sebo
Jonkers, Iris H.
Netea-Maier, Romana T.
Xavier, Ramnik J.
Franke, Lude
Xu, Cheng-Jian
Joosten, Leo A. B.
Sanna, Serena
Jain, Mohit
Kumar, Vinod
Clevers, Hans
Wijmenga, Cisca
Netea, Mihai G.
Li, Yang
author_facet Chu, Xiaojing
Jaeger, Martin
Beumer, Joep
Bakker, Olivier B.
Aguirre-Gamboa, Raul
Oosting, Marije
Smeekens, Sanne P.
Moorlag, Simone
Mourits, Vera P.
Koeken, Valerie A. C. M.
de Bree, Charlotte
Jansen, Trees
Mathews, Ian T.
Dao, Khoi
Najhawan, Mahan
Watrous, Jeramie D.
Joosten, Irma
Sharma, Sonia
Koenen, Hans J. P. M.
Withoff, Sebo
Jonkers, Iris H.
Netea-Maier, Romana T.
Xavier, Ramnik J.
Franke, Lude
Xu, Cheng-Jian
Joosten, Leo A. B.
Sanna, Serena
Jain, Mohit
Kumar, Vinod
Clevers, Hans
Wijmenga, Cisca
Netea, Mihai G.
Li, Yang
author_sort Chu, Xiaojing
collection PubMed
description BACKGROUND: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. RESULT: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target. CONCLUSION: This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02413-z.
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spelling pubmed-82591682021-07-06 Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease Chu, Xiaojing Jaeger, Martin Beumer, Joep Bakker, Olivier B. Aguirre-Gamboa, Raul Oosting, Marije Smeekens, Sanne P. Moorlag, Simone Mourits, Vera P. Koeken, Valerie A. C. M. de Bree, Charlotte Jansen, Trees Mathews, Ian T. Dao, Khoi Najhawan, Mahan Watrous, Jeramie D. Joosten, Irma Sharma, Sonia Koenen, Hans J. P. M. Withoff, Sebo Jonkers, Iris H. Netea-Maier, Romana T. Xavier, Ramnik J. Franke, Lude Xu, Cheng-Jian Joosten, Leo A. B. Sanna, Serena Jain, Mohit Kumar, Vinod Clevers, Hans Wijmenga, Cisca Netea, Mihai G. Li, Yang Genome Biol Research BACKGROUND: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. RESULT: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target. CONCLUSION: This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02413-z. BioMed Central 2021-07-06 /pmc/articles/PMC8259168/ /pubmed/34229738 http://dx.doi.org/10.1186/s13059-021-02413-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chu, Xiaojing
Jaeger, Martin
Beumer, Joep
Bakker, Olivier B.
Aguirre-Gamboa, Raul
Oosting, Marije
Smeekens, Sanne P.
Moorlag, Simone
Mourits, Vera P.
Koeken, Valerie A. C. M.
de Bree, Charlotte
Jansen, Trees
Mathews, Ian T.
Dao, Khoi
Najhawan, Mahan
Watrous, Jeramie D.
Joosten, Irma
Sharma, Sonia
Koenen, Hans J. P. M.
Withoff, Sebo
Jonkers, Iris H.
Netea-Maier, Romana T.
Xavier, Ramnik J.
Franke, Lude
Xu, Cheng-Jian
Joosten, Leo A. B.
Sanna, Serena
Jain, Mohit
Kumar, Vinod
Clevers, Hans
Wijmenga, Cisca
Netea, Mihai G.
Li, Yang
Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
title Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
title_full Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
title_fullStr Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
title_full_unstemmed Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
title_short Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
title_sort integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259168/
https://www.ncbi.nlm.nih.gov/pubmed/34229738
http://dx.doi.org/10.1186/s13059-021-02413-z
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