Dataset Information

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

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 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.

INSTRUMENT(S): Flow injection analysis MS -

SUBMITTER: Xiaojing Chu

PROVIDER: MTBLS2633 | MetaboLights | 2021-06-14

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MTBLS2633	Other
	FILES	Other
	a_MTBLS2633_FIA-MS___metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS2633_FIA-MS___metabolite_profiling_v2_maf.tsv	Tabular

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Publications

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

Chu Xiaojing X Jaeger Martin M Beumer Joep J Bakker Olivier B OB Aguirre-Gamboa Raul R Oosting Marije M Smeekens Sanne P SP Moorlag Simone S Mourits Vera P VP Koeken Valerie A C M VACM de Bree Charlotte C Jansen Trees T Mathews Ian T IT Dao Khoi K Najhawan Mahan M Watrous Jeramie D JD Joosten Irma I Sharma Sonia S Koenen Hans J P M HJPM Withoff Sebo S Jonkers Iris H IH Netea-Maier Romana T RT Xavier Ramnik J RJ Franke Lude L Xu Cheng-Jian CJ Joosten Leo A B LAB Sanna Serena S Jain Mohit M Kumar Vinod V Clevers Hans H Wijmenga Cisca C Netea Mihai G MG Li Yang Y

Genome biology 20210706 1

<h4>Background</h4>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.<h4>Result</h4>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 arachidon ...[more]

PMID: 34229738

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