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Genome-wide DNA methylation study identifies genes associated with the cardiovascular biomarker GDF-15
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 26414697
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 4, 817-827 p.Article in journal (Refereed) Published
Abstract [en]

Growth-differentiation factor 15 (GDF-15) is expressed in low to moderate levels in most healthy tissues and increases in response to inflammation. GDF-15 is associated with cardiovascular dysfunction and over-expressed in the myocardium of patients with myocardial infarction (MI). However, little is known about the function of GDF-15 in cardiovascular disease, and the underlying regulatory network of GDF-15 is not known. To investigate a possible association between GDF-15 levels and DNA methylation, we performed a genome-wide DNA methylation study of white blood cells in a population-based study (N = 717). Significant loci where replicated in an independent cohort (N = 963). We also performed a gene ontology (GO) enrichment analysis. We identified and replicated 16 CpG-sites (false discovery rate [FDR] < 0.05), at 11 independent loci including MIR21. MIR21 encodes a microRNA (miR-21) that has previously been shown to be associated with the development of heart disease. Interestingly, GDF15 mRNA contains a binding site for miR-21. Four sites were also differentially methylated in blood from participants previously diagnosed with MI and 14 enriched GO terms (FDR < 0.05, enrichment > 2) were identified, including 'cardiac muscle cell differentiation'. This study shows that GDF-15 levels are associated with differences in DNA methylation in blood cells, and a subset of the loci are also differentially methylated in participants with MI. However, there might be interactions between GDF-15 levels and methylation in other tissues not addressed in this study. These results provide novel links between GDF-15 and cardiovascular disease.

Place, publisher, year, edition, pages
2016. Vol. 25, no 4, 817-827 p.
National Category
Clinical Medicine Medical Genetics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-275282DOI: 10.1093/hmg/ddv511ISI: 000372151000017PubMedID: 26681806OAI: oai:DiVA.org:uu-275282DiVA: diva2:900607
Funder
Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologySwedish Foundation for Strategic Research EU, European Research Council, 01947 (LSHG-CT-2006-01947)Swedish Society for Medical Research (SSMF)Åke Wiberg FoundationWellcome trust, WT098017
Available from: 2016-02-04 Created: 2016-02-02 Last updated: 2017-11-30Bibliographically approved

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Ek, Weronica EHedman, Åsa KEnroth, StefanGustafsson, StefanGyllensten, UlfLind, LarsJohansson, Åsa

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Ek, Weronica EHedman, Åsa KEnroth, StefanGustafsson, StefanGyllensten, UlfLind, LarsJohansson, Åsa
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Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLabMolecular epidemiologyCardiovascular epidemiology
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Clinical MedicineMedical GeneticsMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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