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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 (author)
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- Salihovic, Samira (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Sundström, Johan (author)
- Uppsala universitet,Kardiovaskulär epidemiologi,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- Broeckling, Corey D (author)
- Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, United States of America
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- Hedman, Åsa K (author)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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- Magnusson, Patrik K E (author)
- Karolinska Institutet
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- Pedersen, Nancy L (author)
- Karolinska Institutet
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- Larsson, Anders (author)
- Uppsala universitet,Biokemisk struktur och funktion
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- Siegbahn, Agneta (author)
- Uppsala universitet,Koagulation och inflammationsvetenskap
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- Zilmer, Mihkel (author)
- Department of Biochemistry, Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia
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- Prenni, Jessica (author)
- Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, United States of America
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- Ärnlöv, Johan (author)
- Högskolan Dalarna,Uppsala universitet,Molekylär epidemiologi,Medicinsk vetenskap
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- Lind, Lars (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Fall, Tove (author)
- Uppsala universitet,Molekylär epidemiologi
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- Ingelsson, Erik (author)
- Uppsala universitet,Molekylär epidemiologi
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(creator_code:org_t)
- 2014-12-11
- 2014
- English.
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:12, s. e1004801-
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Hälsa och välfärd
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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, Åsa K
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Magnusson, Patri ...
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show more...
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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
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Lind, Lars
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Fall, Tove
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Ingelsson, Erik
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Public Health Gl ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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PLOS Genetics
- By the university
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Uppsala University
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Karolinska Institutet
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Högskolan Dalarna