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

Publication ,  Journal Article
Shah, SH; Hauser, ER; Bain, JR; Muehlbauer, MJ; Haynes, C; Stevens, RD; Wenner, BR; Dowdy, ZE; Granger, CB; Ginsburg, GS; Newgard, CB; Kraus, WE
Published in: Mol Syst Biol
2009

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 x 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, beta-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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Published In

Mol Syst Biol

DOI

EISSN

1744-4292

Publication Date

2009

Volume

5

Start / End Page

258

Location

England

Related Subject Headings

  • Principal Component Analysis
  • Middle Aged
  • Metabolome
  • Male
  • Inheritance Patterns
  • Humans
  • Female
  • Fatty Acids
  • Family Health
  • Carnitine
 

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Shah, S. H., Hauser, E. R., Bain, J. R., Muehlbauer, M. J., Haynes, C., Stevens, R. D., … Kraus, W. E. (2009). High heritability of metabolomic profiles in families burdened with premature cardiovascular disease. Mol Syst Biol, 5, 258. https://doi.org/10.1038/msb.2009.11
Shah, Svati H., Elizabeth R. Hauser, James R. Bain, Michael J. Muehlbauer, Carol Haynes, Robert D. Stevens, Brett R. Wenner, et al. “High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.Mol Syst Biol 5 (2009): 258. https://doi.org/10.1038/msb.2009.11.
Shah SH, Hauser ER, Bain JR, Muehlbauer MJ, Haynes C, Stevens RD, et al. High heritability of metabolomic profiles in families burdened with premature cardiovascular disease. Mol Syst Biol. 2009;5:258.
Shah, Svati H., et al. “High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.Mol Syst Biol, vol. 5, 2009, p. 258. Pubmed, doi:10.1038/msb.2009.11.
Shah SH, Hauser ER, Bain JR, Muehlbauer MJ, Haynes C, Stevens RD, Wenner BR, Dowdy ZE, Granger CB, Ginsburg GS, Newgard CB, Kraus WE. High heritability of metabolomic profiles in families burdened with premature cardiovascular disease. Mol Syst Biol. 2009;5:258.
Journal cover image

Published In

Mol Syst Biol

DOI

EISSN

1744-4292

Publication Date

2009

Volume

5

Start / End Page

258

Location

England

Related Subject Headings

  • Principal Component Analysis
  • Middle Aged
  • Metabolome
  • Male
  • Inheritance Patterns
  • Humans
  • Female
  • Fatty Acids
  • Family Health
  • Carnitine