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Large-scale metabol...
Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease
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Ganna, Andrea (författare)
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Salihovic, Samira (författare)
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Sundström, Johan (författare)
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visa fler...
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Broeckling, Corey D (författare)
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Hedman, Asa K (författare)
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Magnusson, Patrik K E (författare)
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Pedersen, Nancy L (författare)
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Larsson, Anders (författare)
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Siegbahn, Agneta (författare)
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Zilmer, Mihkel (författare)
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Prenni, Jessica (författare)
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Ärnlöv, Johan 1970- (författare)
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Lind, Lars (författare)
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Fall, Tove (författare)
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Ingelsson, Erik (författare)
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visa färre...
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(utgivare)
- 2014
- 2014
- Engelska.
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Ingår i: PLOS Genetics. - 1553-7390. ; 10 12
Abstract
Ämnesord
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- 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.
Ämnesord
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Health and Welfare (du)
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Ganna, Andrea
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Salihovic, Samir ...
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Sundström, Johan
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Broeckling, Core ...
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Hedman, Asa K
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Magnusson, Patri ...
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visa fler...
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Pedersen, Nancy ...
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Larsson, Anders
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Siegbahn, Agneta
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Zilmer, Mihkel
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Prenni, Jessica
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Ärnlöv, Johan 19 ...
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Lind, Lars
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Fall, Tove
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Ingelsson, Erik
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visa färre...
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