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  • Ganna, AndreaDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (author)

Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-12-11
  • Public Library of Science (PLoS),2014
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-239007
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-239007URI
  • https://doi.org/10.1371/journal.pgen.1004801DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:130416875URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:du-16604URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Salihovic, SamiraUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)samsa560 (author)
  • Sundström, JohanUppsala universitet,Kardiovaskulär epidemiologi,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden(Swepub:uu)johasund (author)
  • Broeckling, Corey DProteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, United States of America (author)
  • Hedman, Åsa KUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ashed124 (author)
  • Magnusson, Patrik K EKarolinska Institutet (author)
  • Pedersen, Nancy LKarolinska Institutet (author)
  • Larsson, AndersUppsala universitet,Biokemisk struktur och funktion(Swepub:uu)andlarss (author)
  • Siegbahn, AgnetaUppsala universitet,Koagulation och inflammationsvetenskap(Swepub:uu)agsie424 (author)
  • Zilmer, MihkelDepartment of Biochemistry, Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia (author)
  • Prenni, JessicaProteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, United States of America (author)
  • Ärnlöv, JohanHögskolan Dalarna,Uppsala universitet,Molekylär epidemiologi,Medicinsk vetenskap(Swepub:du)jan (author)
  • Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
  • Fall, ToveUppsala universitet,Molekylär epidemiologi(Swepub:uu)tovfa878 (author)
  • Ingelsson, ErikUppsala universitet,Molekylär epidemiologi(Swepub:uu)ering425 (author)
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenKardiovaskulär epidemiologi (creator_code:org_t)

Related titles

  • In:PLOS Genetics: Public Library of Science (PLoS)10:12, s. e1004801-1553-73901553-7404

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