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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • 2009

Published In

Volume / Issue

  • 5 /

Start / End Page

  • 258 -

PubMed ID

  • 19357637

Pubmed Central ID

  • PMC2683717

Electronic International Standard Serial Number (EISSN)

  • 1744-4292

Digital Object Identifier (DOI)

  • 10.1038/msb.2009.11


  • eng

Conference Location

  • England