High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.
High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.
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DOI：
10.1038/msb.2009.11
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发表时间：
2009
影响因子：
9.9
通讯作者：
Kraus, William E.
中科院分区：
文献类型：
--
作者：
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.
基因和新陈代谢图谱的整合有望提供对人类疾病的洞察。冠状动脉疾病(CAD)具有很强的遗传性，但代谢组谱的遗传性在人类中尚未得到评估。我们对来自GENECARD早产儿CAD研究的八个多重家系的117个个体进行了基于定量质谱学的代谢特征分析。遗传力用方差分量计算。氨基酸(精氨酸、鸟氨酸、丙氨酸、丙氨酸、亮氨酸/异亮氨酸、缬氨酸、谷氨酸/谷氨酰胺、苯丙氨酸和甘氨酸)、游离脂肪酸(花生四烯酸、棕榈酸、亚油酸；H2=0.48~0.59，P=0.002~0.00005)和酰基肉碱(H2=0.23~0.79，P=0.0000002)具有较高的遗传力。主成分分析用于识别代谢物簇。反映单个代谢物的几种成分是可遗传的，包括酮、β-羟基丁酸酯和C2-酰基肉碱(H2=0.61)；短链和中链酰基肉碱(H2=0.39)；氨基酸(H2=0.44)；长链酰基肉碱(H2=0.39)和支链氨基酸(H2=0.27)。我们报告了一项新的发现，在早产儿冠心病中代谢产物的高遗传性，建立了这些特征的可能的遗传学基础。这些结果对了解CAD的病理生理学和遗传学具有重要意义。
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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影响因子：
4.5
作者：
Ferrara CT;Wang P;Neto EC;Stevens RD;Bain JR;Wenner BR;Ilkayeva OR;Keller MP;Blasiole DA;Kendziorski C;Yandell BS;Newgard CB;Attie AD
通讯作者：
Attie AD
影响因子：
30.8
作者：
Keurentjes, Joost J. B.;Fu, Jingyuan;Koornneef, Maarten
通讯作者：
Koornneef, Maarten
DOI：
10.1375/1369052022956
发表时间：
2002-04-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Beekman, M;Heijmans, BT;Boomsma, DI
通讯作者：
Boomsma, DI
影响因子：
1.9
作者：
Shah, S. H.;Kraus, W. E.;Hauser, E. R.
通讯作者：
Hauser, E. R.
影响因子：
15.9
作者：
Wu, JY;Kao, HJ;Chen, YT
通讯作者：
Chen, YT