Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• PLoS genetics, 2014-12, Vol.10 (12), p.e1004801-e1004801

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.