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Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease

PLoS genetics, 2014-12, Vol.10 (12), p.e1004801-e1004801 [Peer Reviewed Journal]

COPYRIGHT 2014 Public Library of Science ;COPYRIGHT 2014 Public Library of Science ;2014 Ganna et al 2014 Ganna et al ;2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Ganna A, Salihovic S, Sundström J, Broeckling CD, Hedman ÅK, Magnusson PKE, et al. (2014) Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease. PLoS Genet 10(12): e1004801. doi:10.1371/journal.pgen.1004801 ;ISSN: 1553-7404 ;ISSN: 1553-7390 ;EISSN: 1553-7404 ;DOI: 10.1371/journal.pgen.1004801 ;PMID: 25502724

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Title:
Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease
Author: Ganna, Andrea ; Salihovic, Samira ; Sundström, Johan ; Broeckling, Corey D ; Hedman, Asa K ; Magnusson, Patrik K E ; Pedersen, Nancy L ; Larsson, Anders ; Siegbahn, Agneta ; Zilmer, Mihkel ; Prenni, Jessica ; Arnlöv, Johan ; Lind, Lars ; Fall, Tove ; Ingelsson, Erik
Gibson, Greg
Subjects: Aged ; Biology and Life Sciences ; Biomarkers - blood ; C-Reactive Protein - metabolism ; Cardiovascular disease ; Coronary Disease - blood ; Coronary Disease - epidemiology ; Coronary Disease - genetics ; Coronary heart disease ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Genetic aspects ; Genetic Association Studies ; Health and Welfare ; Health risk assessment ; Humans ; Hälsa och välfärd ; Incidence ; Linear Models ; Longitudinal Studies ; Lysophosphatidylcholines - blood ; Male ; Medicin och hälsovetenskap ; Metabolism ; Metabolites ; Metabolomics ; Methods ; Middle Aged ; Monoglycerides - blood ; Polymorphism, Single Nucleotide ; Prevalence studies (Epidemiology) ; Prospective Studies ; Reproducibility of Results ; Risk Assessment ; Risk Factors ; Sphingomyelins - blood ; Statistics ; Studies ; Sweden
Is Part Of: PLoS genetics, 2014-12, Vol.10 (12), p.e1004801-e1004801
Description: Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1553-7404
ISSN: 1553-7390
EISSN: 1553-7404
DOI: 10.1371/journal.pgen.1004801
PMID: 25502724
Source: Public Library of Science (PLoS) Journals Open Access
GFMER Free Medical Journals
MEDLINE
PubMed Central
SWEPUB Freely available online
ProQuest Central
DOAJ Directory of Open Access Journals

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Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease

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