Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009:5:258.
doi: 10.1038/msb.2009.11. Epub 2009 Apr 7.

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

Svati H Shah  1 , Elizabeth R Hauser, James R Bain, Michael J Muehlbauer, Carol Haynes, Robert D Stevens, Brett R Wenner, Z Elaine Dowdy, Christopher B Granger, Geoffrey S Ginsburg, Christopher B Newgard, William E Kraus
Affiliations

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

Svati H Shah et al. Mol Syst Biol. 2009.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Heritabilities of conventional metabolites. Heritabilities of the conventional metabolites are displayed in graphical form. The Y-axis is the negative log10 of the P-value for the heritability estimate (X-axis). Error bars around heritability point estimates are in light gray.
Figure 2
Figure 2
Heritabilities of amino acids and free fatty acids. Heritabilities of amino acids and free fatty acids are displayed in graphical form. The Y-axis is the negative log10 of the P-value for the heritability estimate (X-axis). Error bars around heritability point estimates are in light gray.
Figure 3
Figure 3
Heritabilities of acylcarnitines. Heritabilities of the acylcarnitines are displayed in graphical form. The Y-axis is the negative log10 of the P-value for the heritability estimate (X-axis). Error bars around heritability point estimates are in light gray.
See this image and copyright information in PMC

References

    1. Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62: 1198–1211 - PMC - PubMed
    1. An J, Muoio DM, Shiota M, Fujimoto Y, Cline GW, Shulman GI, Koves TR, Stevens R, Millington D, Newgard CB (2004) Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat Med 10: 268–274 - PubMed
    1. Beekman M, Heijmans BT, Martin NG, Pedersen NL, Whitfield JB, DeFaire U, van Baal GC, Snieder H, Vogler GP, Slagboom PE, Boomsma DI (2002) Heritabilities of apolipoprotein and lipid levels in three countries. Twin Res 5: 87–97 - PubMed
    1. Brindle JT, Antti H, Holmes E, Tranter G, Nicholson JK, Bethell HW, Clarke S, Schofield PM, McKilligin E, Mosedale DE, Grainger DJ (2002) Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat Med 8: 1439–1444 - PubMed
    1. Chace DH, Hillman SL, Millington DS, Kahler SG, Roe CR, Naylor EW (1995) Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry. Clin Chem 41: 62–68 - PubMed

Publication types