Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
| العنوان: | Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease |
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| المؤلفون: | Ian T. Mathews, Yang Li, Valerie A. C. M. Koeken, Sonia Sharma, Mihai G. Netea, Trees Jansen, Charlotte de Bree, Mahan Najhawan, Vera P. Mourits, Sebo Withoff, Olivier B. Bakker, Marije Oosting, Simone J.C.F.M. Moorlag, Jeramie D. Watrous, Vinod Kumar, Sanne P. Smeekens, Serena Sanna, Ramnik J. Xavier, Joep Beumer, Martin Jaeger, Hans J. P. M. Koenen, Lude Franke, Leo A. B. Joosten, Iris Jonkers, Raul Aguirre-Gamboa, Cisca Wijmenga, Romana T. Netea-Maier, Mohit Jain, Hans Clevers, Cheng-Jian Xu, Xiaojing Chu, Irma Joosten, Khoi Dao |
| المساهمون: | Hubrecht Institute for Developmental Biology and Stem Cell Research, Molecular Neuroscience and Ageing Research (MOLAR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover., TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany., BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany. |
| المصدر: | Genome Biology, 22(1). BioMed Central Genome Biology, 22, 1 Genome Biology, 22 Genome Biology Genome Biology, Vol 22, Iss 1, Pp 1-22 (2021) Genome Biology, 22(1):198. BMC Genome biology United States International England |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Metabolite, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Immune phenotypes, Disease, VARIANTS, SUSCEPTIBILITY, QH426-470, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, RARE, WIDE ASSOCIATION, Biology (General), POLYUNSATURATED FATTY-ACIDS, Genetics, Alanine, Arachidonic Acid, Genomics, Middle Aged, CROHNS-DISEASE, Healthy Volunteers, Phenotype, MENDELIAN RANDOMIZATION, GENETIC-FACTORS, Female, Metabolic Networks and Pathways, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], EXPRESSION, Adult, Adolescent, QH301-705.5, Quantitative Trait Loci, Glutamic Acid, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Biology, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Metabolomics, Immune system, Metabolome, Humans, COMMON, Aged, Research, Integrative analysis, Immunity, Innate, Human genetics, Metabolic pathway, 030104 developmental biology, chemistry, 030217 neurology & neurosurgery, Genome-Wide Association Study |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1474-760X 1474-7596 1465-6906 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ca2418c59e637207e61226dad14da6aTest https://doi.org/10.1186/s13059-021-02413-zTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1ca2418c59e637207e61226dad14da6a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1474760X 14747596 14656906 |
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