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High heritability of metabolomic profiles in families burdened with premature cardiovascular disease

Integration of genetic and metabolic profiling holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolomic profiles has not been evaluated in humans. We performed quantitative mass spectrometry-based metabolic profi...

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Autores principales: Shah, Svati H, Hauser, Elizabeth R, Bain, James R, Muehlbauer, Michael J, Haynes, Carol, Stevens, Robert D, Wenner, Brett R, Dowdy, Z Elaine, Granger, Christopher B, Ginsburg, Geoffrey S, Newgard, Christopher B, Kraus, William E
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683717/
https://www.ncbi.nlm.nih.gov/pubmed/19357637
http://dx.doi.org/10.1038/msb.2009.11
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author Shah, Svati H
Hauser, Elizabeth R
Bain, James R
Muehlbauer, Michael J
Haynes, Carol
Stevens, Robert D
Wenner, Brett R
Dowdy, Z Elaine
Granger, Christopher B
Ginsburg, Geoffrey S
Newgard, Christopher B
Kraus, William E
author_facet Shah, Svati H
Hauser, Elizabeth R
Bain, James R
Muehlbauer, Michael J
Haynes, Carol
Stevens, Robert D
Wenner, Brett R
Dowdy, Z Elaine
Granger, Christopher B
Ginsburg, Geoffrey S
Newgard, Christopher B
Kraus, William E
author_sort Shah, Svati H
collection PubMed
description Integration of genetic and metabolic profiling holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolomic profiles has not been evaluated in humans. We performed quantitative mass spectrometry-based metabolic profiling in 117 individuals within eight multiplex families from the GENECARD study of premature CAD. Heritabilities were calculated using variance components. We found high heritabilities for amino acids (arginine, ornithine, alanine, proline, leucine/isoleucine, valine, glutamate/glutamine, phenylalanine and glycine; h(2)=0.33–0.80, P=0.005–1.9 × 10(−16)), free fatty acids (arachidonic, palmitic, linoleic; h(2)=0.48–0.59, P=0.002–0.00005) and acylcarnitines (h(2)=0.23–0.79, P=0.05–0.0000002). Principal components analysis was used to identify metabolite clusters. Reflecting individual metabolites, several components were heritable, including components comprised of ketones, β-hydroxybutyrate and C2-acylcarnitine (h(2)=0.61); short- and medium-chain acylcarnitines (h(2)=0.39); amino acids (h(2)=0.44); long-chain acylcarnitines (h(2)=0.39) and branched-chain amino acids (h(2)=0.27). We report a novel finding of high heritabilities of metabolites in premature CAD, establishing a possible genetic basis for these profiles. These results have implications for understanding CAD pathophysiology and genetics.
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spelling pubmed-26837172009-05-18 High heritability of metabolomic profiles in families burdened with premature cardiovascular disease Shah, Svati H Hauser, Elizabeth R Bain, James R Muehlbauer, Michael J Haynes, Carol Stevens, Robert D Wenner, Brett R Dowdy, Z Elaine Granger, Christopher B Ginsburg, Geoffrey S Newgard, Christopher B Kraus, William E Mol Syst Biol Report Integration of genetic and metabolic profiling holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolomic profiles has not been evaluated in humans. We performed quantitative mass spectrometry-based metabolic profiling in 117 individuals within eight multiplex families from the GENECARD study of premature CAD. Heritabilities were calculated using variance components. We found high heritabilities for amino acids (arginine, ornithine, alanine, proline, leucine/isoleucine, valine, glutamate/glutamine, phenylalanine and glycine; h(2)=0.33–0.80, P=0.005–1.9 × 10(−16)), free fatty acids (arachidonic, palmitic, linoleic; h(2)=0.48–0.59, P=0.002–0.00005) and acylcarnitines (h(2)=0.23–0.79, P=0.05–0.0000002). Principal components analysis was used to identify metabolite clusters. Reflecting individual metabolites, several components were heritable, including components comprised of ketones, β-hydroxybutyrate and C2-acylcarnitine (h(2)=0.61); short- and medium-chain acylcarnitines (h(2)=0.39); amino acids (h(2)=0.44); long-chain acylcarnitines (h(2)=0.39) and branched-chain amino acids (h(2)=0.27). We report a novel finding of high heritabilities of metabolites in premature CAD, establishing a possible genetic basis for these profiles. These results have implications for understanding CAD pathophysiology and genetics. Nature Publishing Group 2009-04-07 /pmc/articles/PMC2683717/ /pubmed/19357637 http://dx.doi.org/10.1038/msb.2009.11 Text en Copyright © 2009, EMBO and Nature Publishing Group http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation or the creation of derivative works without specific permission.
spellingShingle Report
Shah, Svati H
Hauser, Elizabeth R
Bain, James R
Muehlbauer, Michael J
Haynes, Carol
Stevens, Robert D
Wenner, Brett R
Dowdy, Z Elaine
Granger, Christopher B
Ginsburg, Geoffrey S
Newgard, Christopher B
Kraus, William E
High heritability of metabolomic profiles in families burdened with premature cardiovascular disease
title High heritability of metabolomic profiles in families burdened with premature cardiovascular disease
title_full High heritability of metabolomic profiles in families burdened with premature cardiovascular disease
title_fullStr High heritability of metabolomic profiles in families burdened with premature cardiovascular disease
title_full_unstemmed High heritability of metabolomic profiles in families burdened with premature cardiovascular disease
title_short High heritability of metabolomic profiles in families burdened with premature cardiovascular disease
title_sort high heritability of metabolomic profiles in families burdened with premature cardiovascular disease
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683717/
https://www.ncbi.nlm.nih.gov/pubmed/19357637
http://dx.doi.org/10.1038/msb.2009.11
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