A genome-wide association study of the human metabolome in a community-based cohort

Because metabolites are hypothesized to play key roles as markers and effectors of cardiometabolic diseases, recent studies have sought to annotate the genetic determinants of circulating metabolite levels. We report a genome-wide association study (GWAS) of 217 plasma metabolites, including >100...

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Veröffentlicht in:Cell metabolism Jg. 18; H. 1; S. 130
Hauptverfasser: Rhee, Eugene P, Ho, Jennifer E, Chen, Ming-Huei, Shen, Dongxiao, Cheng, Susan, Larson, Martin G, Ghorbani, Anahita, Shi, Xu, Helenius, Iiro T, O'Donnell, Christopher J, Souza, Amanda L, Deik, Amy, Pierce, Kerry A, Bullock, Kevin, Walford, Geoffrey A, Vasan, Ramachandran S, Florez, Jose C, Clish, Clary, Yeh, J-R Joanna, Wang, Thomas J, Gerszten, Robert E
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 02.07.2013
Schlagworte:
Aged
Cholesterol Esters - metabolism
Cohort Studies
Community Participation
Female
Genome, Human - genetics
Genome-Wide Association Study
Humans
Male
Massachusetts
Metabolome - genetics
Middle Aged
Transaminases - genetics
Transaminases - metabolism
Triglycerides - metabolism
ISSN:1932-7420, 1932-7420
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Zusammenfassung:Because metabolites are hypothesized to play key roles as markers and effectors of cardiometabolic diseases, recent studies have sought to annotate the genetic determinants of circulating metabolite levels. We report a genome-wide association study (GWAS) of 217 plasma metabolites, including >100 not measured in prior GWAS, in 2076 participants of the Framingham Heart Study (FHS). For the majority of analytes, we find that estimated heritability explains >20% of interindividual variation, and that variation attributable to heritable factors is greater than that attributable to clinical factors. Further, we identify 31 genetic loci associated with plasma metabolites, including 23 that have not previously been reported. Importantly, we include GWAS results for all surveyed metabolites and demonstrate how this information highlights a role for AGXT2 in cholesterol ester and triacylglycerol metabolism. Thus, our study outlines the relative contributions of inherited and clinical factors on the plasma metabolome and provides a resource for metabolism research.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2013.06.013