High heritability of metabolomic profiles in families burdened with premature cardiovascular disease |
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Authors: | Svati H Shah 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 |
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Affiliation: | 1. Department of Medicine, Duke University Medical Center, Durham, NC, USA;2. Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC, USA;3. Sarah W Stedman Nutrition and Metabolism Center, Duke University, Durham, NC, USA;4. Institute for Genome Sciences & Policy, Duke University Medical Center, Durham, NC, USA;5. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA |
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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; h2=0.33–0.80, P=0.005–1.9 × 10?16), free fatty acids (arachidonic, palmitic, linoleic; h2=0.48–0.59, P=0.002–0.00005) and acylcarnitines (h2=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 (h2=0.61); short‐ and medium‐chain acylcarnitines (h2=0.39); amino acids (h2=0.44); long‐chain acylcarnitines (h2=0.39) and branched‐chain amino acids (h2=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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Keywords: | acylcarnitines amino acids heritability cardiovascular disease metabolomics |
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