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Cell Metab DOI:10.1016/j.cmet.2013.06.013

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

Publication TypeJournal Article
Year of Publication2013
AuthorsRhee, EP, Ho, JE, Chen, M-H, 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, J-RJoanna, Wang, TJ, Gerszten, RE
JournalCell Metab
Volume18
Issue1
Pages130-43
Date Published2013 Jul 02
ISSN1932-7420
KeywordsAged, Cholesterol Esters, Cohort Studies, Community Participation, Female, Genome, Human, Genome-Wide Association Study, Humans, Male, Massachusetts, Metabolome, Middle Aged, Transaminases, Triglycerides
Abstract

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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1550-4131(13)00257-X
DOI10.1016/j.cmet.2013.06.013
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23823483?dopt=Abstract

Alternate JournalCell Metab.
PubMed ID23823483
PubMed Central IDPMC3973158
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
K23-HL-116780 / HL / NHLBI NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R-01-HL-093328 / HL / NHLBI NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
R01-HL-098280 / HL / NHLBI NIH HHS / United States
R01 HL098280 / HL / NHLBI NIH HHS / United States
R01 HL081572 / HL / NHLBI NIH HHS / United States
K08-DK-090142 / DK / NIDDK NIH HHS / United States
R01-DK-HL-081572 / DK / NIDDK NIH HHS / United States
K08 DK090142 / DK / NIDDK NIH HHS / United States
K23 HL116780 / HL / NHLBI NIH HHS / United States
R01 HL093328 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
U01-HL-107440 / HL / NHLBI NIH HHS / United States
U01 HL107440 / HL / NHLBI NIH HHS / United States