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

Rhee EP, Ho JE, Chen MH, Shen D, Cheng S, Larson MG, Ghorbani A, Shi X, Helenius IT, O'Donnell CJ, Souza AL, Deik A, Pierce KA, Bullock K, Walford GA, Vasan RS, Florez JC, Clish C, Yeh JR, Wang TJ, Gerszten RE
Cell Metab. 2013 18 (1): 130-43

PMID: 23823483 · PMCID: PMC3973158 · DOI:10.1016/j.cmet.2013.06.013

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (14)

Aged Cholesterol Esters Cohort Studies Community Participation Female Genome, Human Genome-Wide Association Study Humans Male Massachusetts Metabolome Middle Aged Transaminases Triglycerides

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