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.
  
  
  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.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Claire
authors.initials: C
authors.lastname: Bellis
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Manju
authors.initials: M
authors.lastname: Mamtani
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne VIC, Australia.
authors.forename: Gerard
authors.initials: G
authors.lastname: Wong
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne VIC, Australia.
authors.forename: Jacquelyn M
authors.initials: JM
authors.lastname: Weir
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne VIC, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Barlow
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Vincent
authors.initials: V
authors.lastname: Diego
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Marcio
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Harald H H
authors.initials: HHH
authors.lastname: Göring
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.|Southwest National Primate Research Center, San Antonio, TX.
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams-Blangero
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne VIC, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors
chemical_list: D008055:Lipids
keywords: cardiovascular diseases; genetics; lipids