Abstract

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.

Details

Title
Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Author
Chu, Xiaojing; Jaeger, Martin; Beumer, Joep; Bakker, Olivier B; Aguirre-Gamboa, Raul; Oosting, Marije; Smeekens, Sanne P; Moorlag, Simone; Mourits, Vera P; Valerie A. C. M. Koeken; de Bree, Charlotte; Jansen, Trees; Mathews, Ian T; Dao, Khoi; Mahan Najhawan; Watrous, Jeramie D; Joosten, Irma; Sharma, Sonia; Hans J. P. M. Koenen; Sebo Withoff; Jonkers, Iris H; Netea-Maier, Romana T; Xavier, Ramnik J; Franke, Lude; Cheng-Jian, Xu; Joosten, Leo A B; Sanna, Serena; Jain, Mohit; Kumar, Vinod; Clevers, Hans; Wijmenga, Cisca; Netea, Mihai G; Yang, Li  VIAFID ORCID Logo 
Pages
1-22
Section
Research
Publication year
2021
Publication date
2021
Publisher
BioMed Central
ISSN
14747596
e-ISSN
1474760X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s13059-021-02413-z
ProQuest document ID
2553256414
Copyright
© 2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.