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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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.
AbstractList	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. 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.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.
Author	Helenius, Iiro T Vasan, Ramachandran S Cheng, Susan Wang, Thomas J O'Donnell, Christopher J Rhee, Eugene P Ghorbani, Anahita Walford, Geoffrey A Bullock, Kevin Chen, Ming-Huei Gerszten, Robert E Shen, Dongxiao Souza, Amanda L Deik, Amy Larson, Martin G Pierce, Kerry A Ho, Jennifer E Clish, Clary Florez, Jose C Yeh, J-R Joanna Shi, Xu
Author_xml	– sequence: 1 givenname: Eugene P surname: Rhee fullname: Rhee, Eugene P organization: Nephrology Division, Massachusetts General Hospital, Boston, MA 02114, USA – sequence: 2 givenname: Jennifer E surname: Ho fullname: Ho, Jennifer E – sequence: 3 givenname: Ming-Huei surname: Chen fullname: Chen, Ming-Huei – sequence: 4 givenname: Dongxiao surname: Shen fullname: Shen, Dongxiao – sequence: 5 givenname: Susan surname: Cheng fullname: Cheng, Susan – sequence: 6 givenname: Martin G surname: Larson fullname: Larson, Martin G – sequence: 7 givenname: Anahita surname: Ghorbani fullname: Ghorbani, Anahita – sequence: 8 givenname: Xu surname: Shi fullname: Shi, Xu – sequence: 9 givenname: Iiro T surname: Helenius fullname: Helenius, Iiro T – sequence: 10 givenname: Christopher J surname: O'Donnell fullname: O'Donnell, Christopher J – sequence: 11 givenname: Amanda L surname: Souza fullname: Souza, Amanda L – sequence: 12 givenname: Amy surname: Deik fullname: Deik, Amy – sequence: 13 givenname: Kerry A surname: Pierce fullname: Pierce, Kerry A – sequence: 14 givenname: Kevin surname: Bullock fullname: Bullock, Kevin – sequence: 15 givenname: Geoffrey A surname: Walford fullname: Walford, Geoffrey A – sequence: 16 givenname: Ramachandran S surname: Vasan fullname: Vasan, Ramachandran S – sequence: 17 givenname: Jose C surname: Florez fullname: Florez, Jose C – sequence: 18 givenname: Clary surname: Clish fullname: Clish, Clary – sequence: 19 givenname: J-R Joanna surname: Yeh fullname: Yeh, J-R Joanna – sequence: 20 givenname: Thomas J surname: Wang fullname: Wang, Thomas J – sequence: 21 givenname: Robert E surname: Gerszten fullname: Gerszten, Robert E
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23823483$$D View this record in MEDLINE/PubMed
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SubjectTerms	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
Title	A genome-wide association study of the human metabolome in a community-based cohort
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