Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease.
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Authors
Chu, XiaojingJaeger, 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
Issue Date
2021-07-06
Metadata
Show full item recordAbstract
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.Citation
Genome Biol. 2021 Jul 6;22(1):198. doi: 10.1186/s13059-021-02413-z.Affiliation
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.Publisher
BMCJournal
Genome biologyPubMed ID
34229738Type
ArticleLanguage
enEISSN
1474-760Xae974a485f413a2113503eed53cd6c53
10.1186/s13059-021-02413-z
Scopus Count
The following license files are associated with this item:
- Creative Commons