Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death

Claire Bellis, Hemant Kulkarni, Manju Mamtani, Jack W Kent Jr, Gerard Wong, Jacquelyn M Weir, Christopher K. Barlow, Vincent Diego, Marcio A Alfonso de Almeida, Thomas D Dyer, Harald H H Göring, Laura Almasy, Michael C Mahaney, Anthony G Comuzzie, Sarah Williams-Blangero, Peter J. Meikle, John Blangero, Joanne E Curran

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background-Cardiovascular disease (CVD) is the most common cause of death in the United States and is associated with a high economic burden. Prevention of CVD focuses on controlling or improving the lipid profile of patients at risk. The human lipidome is made up of thousands of ubiquitous lipid species. By studying biologically simple canonical lipid species, we investigated whether the lipidome is genetically redundant and whether its genetic influences can provide clinically relevant clues of CVD risk. Methods and Results-We performed a genetic study of the human lipidome in 1212 individuals from 42 extended Mexican American families. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing 319 unique species. Using variance component-based heritability analyses and bivariate trait analyses, we detected significant genetic influences on each lipid assayed. Median heritability of the plasma lipid species was 0.37. Hierarchical clustering based on complex genetic correlation patterns identified 12 genetic clusters that characterized the plasma lipidome. These genetic clusters were differentially but consistently associated with risk factors of CVD, including central obesity, obesity, type 2 diabetes mellitus, raised serum triglycerides, and metabolic syndrome. Also, these clusters consistently predicted occurrence of cardiovascular deaths during follow-up. Conclusions-The human plasma lipidome is heritable. Shared genetic influences reduce the dimensionality of the human lipidome into clusters that are associated with risk factors of CVD.

Original languageEnglish
Pages (from-to)854-863
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume7
Issue number6
DOIs
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Keywords

  • Cardiovascular diseases
  • Genetics
  • Lipids

Cite this

Bellis, C., Kulkarni, H., Mamtani, M., Kent Jr, J. W., Wong, G., Weir, J. M., ... Curran, J. E. (2014). Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death. Circulation: Cardiovascular Genetics, 7(6), 854-863. https://doi.org/10.1161/CIRCGENETICS.114.000600
Bellis, Claire ; Kulkarni, Hemant ; Mamtani, Manju ; Kent Jr, Jack W ; Wong, Gerard ; Weir, Jacquelyn M ; Barlow, Christopher K. ; Diego, Vincent ; de Almeida, Marcio A Alfonso ; Dyer, Thomas D ; Göring, Harald H H ; Almasy, Laura ; Mahaney, Michael C ; Comuzzie, Anthony G ; Williams-Blangero, Sarah ; Meikle, Peter J. ; Blangero, John ; Curran, Joanne E. / Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death. In: Circulation: Cardiovascular Genetics. 2014 ; Vol. 7, No. 6. pp. 854-863.
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title = "Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death",
abstract = "Background-Cardiovascular disease (CVD) is the most common cause of death in the United States and is associated with a high economic burden. Prevention of CVD focuses on controlling or improving the lipid profile of patients at risk. The human lipidome is made up of thousands of ubiquitous lipid species. By studying biologically simple canonical lipid species, we investigated whether the lipidome is genetically redundant and whether its genetic influences can provide clinically relevant clues of CVD risk. Methods and Results-We performed a genetic study of the human lipidome in 1212 individuals from 42 extended Mexican American families. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing 319 unique species. Using variance component-based heritability analyses and bivariate trait analyses, we detected significant genetic influences on each lipid assayed. Median heritability of the plasma lipid species was 0.37. Hierarchical clustering based on complex genetic correlation patterns identified 12 genetic clusters that characterized the plasma lipidome. These genetic clusters were differentially but consistently associated with risk factors of CVD, including central obesity, obesity, type 2 diabetes mellitus, raised serum triglycerides, and metabolic syndrome. Also, these clusters consistently predicted occurrence of cardiovascular deaths during follow-up. Conclusions-The human plasma lipidome is heritable. Shared genetic influences reduce the dimensionality of the human lipidome into clusters that are associated with risk factors of CVD.",
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author = "Claire Bellis and Hemant Kulkarni and Manju Mamtani and {Kent Jr}, {Jack W} and Gerard Wong and Weir, {Jacquelyn M} and Barlow, {Christopher K.} and Vincent Diego and {de Almeida}, {Marcio A Alfonso} and Dyer, {Thomas D} and G{\"o}ring, {Harald H H} and Laura Almasy and Mahaney, {Michael C} and Comuzzie, {Anthony G} and Sarah Williams-Blangero and Meikle, {Peter J.} and John Blangero and Curran, {Joanne E}",
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Bellis, C, Kulkarni, H, Mamtani, M, Kent Jr, JW, Wong, G, Weir, JM, Barlow, CK, Diego, V, de Almeida, MAA, Dyer, TD, Göring, HHH, Almasy, L, Mahaney, MC, Comuzzie, AG, Williams-Blangero, S, Meikle, PJ, Blangero, J & Curran, JE 2014, 'Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death' Circulation: Cardiovascular Genetics, vol. 7, no. 6, pp. 854-863. https://doi.org/10.1161/CIRCGENETICS.114.000600

Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death. / Bellis, Claire; Kulkarni, Hemant; Mamtani, Manju; Kent Jr, Jack W; Wong, Gerard; Weir, Jacquelyn M; Barlow, Christopher K.; Diego, Vincent; de Almeida, Marcio A Alfonso; Dyer, Thomas D; Göring, Harald H H; Almasy, Laura; Mahaney, Michael C; Comuzzie, Anthony G; Williams-Blangero, Sarah ; Meikle, Peter J.; Blangero, John; Curran, Joanne E.

In: Circulation: Cardiovascular Genetics, Vol. 7, No. 6, 01.12.2014, p. 854-863.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Human plasma lipidome is pleiotropically associated with cardiovascular risk factors and death

AU - Bellis, Claire

AU - Kulkarni, Hemant

AU - Mamtani, Manju

AU - Kent Jr, Jack W

AU - Wong, Gerard

AU - Weir, Jacquelyn M

AU - Barlow, Christopher K.

AU - Diego, Vincent

AU - de Almeida, Marcio A Alfonso

AU - Dyer, Thomas D

AU - Göring, Harald H H

AU - Almasy, Laura

AU - Mahaney, Michael C

AU - Comuzzie, Anthony G

AU - Williams-Blangero, Sarah

AU - Meikle, Peter J.

AU - Blangero, John

AU - Curran, Joanne E

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Background-Cardiovascular disease (CVD) is the most common cause of death in the United States and is associated with a high economic burden. Prevention of CVD focuses on controlling or improving the lipid profile of patients at risk. The human lipidome is made up of thousands of ubiquitous lipid species. By studying biologically simple canonical lipid species, we investigated whether the lipidome is genetically redundant and whether its genetic influences can provide clinically relevant clues of CVD risk. Methods and Results-We performed a genetic study of the human lipidome in 1212 individuals from 42 extended Mexican American families. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing 319 unique species. Using variance component-based heritability analyses and bivariate trait analyses, we detected significant genetic influences on each lipid assayed. Median heritability of the plasma lipid species was 0.37. Hierarchical clustering based on complex genetic correlation patterns identified 12 genetic clusters that characterized the plasma lipidome. These genetic clusters were differentially but consistently associated with risk factors of CVD, including central obesity, obesity, type 2 diabetes mellitus, raised serum triglycerides, and metabolic syndrome. Also, these clusters consistently predicted occurrence of cardiovascular deaths during follow-up. Conclusions-The human plasma lipidome is heritable. Shared genetic influences reduce the dimensionality of the human lipidome into clusters that are associated with risk factors of CVD.

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KW - Cardiovascular diseases

KW - Genetics

KW - Lipids

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