Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146162
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dc.contributor.authorGomez-Alonso, Monica del C.en_US
dc.contributor.authorKretschmer, Anjaen_US
dc.contributor.authorWilson, Roryen_US
dc.contributor.authorPfeiffer, Lilianeen_US
dc.contributor.authorKarhunen, Villeen_US
dc.contributor.authorSeppälä, Ilkkaen_US
dc.contributor.authorZhang, Weihuaen_US
dc.contributor.authorMittelstraß, Kirstinen_US
dc.contributor.authorWahl, Simoneen_US
dc.contributor.authorMatias-Garcia, Pamela R.en_US
dc.contributor.authorProkisch, Holgeren_US
dc.contributor.authorHorn, Sachaen_US
dc.contributor.authorMeitinger, Thomasen_US
dc.contributor.authorSerrano-Garcia, Luis R.en_US
dc.contributor.authorSebert, Sylvainen_US
dc.contributor.authorRaitakari, Ollien_US
dc.contributor.authorLoh, Marieen_US
dc.contributor.authorRathmann, Wolfgangen_US
dc.contributor.authorMüller-Nurasyid, Martinaen_US
dc.contributor.authorHerder, Christianen_US
dc.contributor.authorRoden, Michaelen_US
dc.contributor.authorHurme, Mikkoen_US
dc.contributor.authorJarvelin, Marjo-Riittaen_US
dc.contributor.authorAla-Korpela, Mikaen_US
dc.contributor.authorKooner, Jaspal S.en_US
dc.contributor.authorPeters, Annetteen_US
dc.contributor.authorLehtimäki, Terhoen_US
dc.contributor.authorChambers, John Campbellen_US
dc.contributor.authorGieger, Christianen_US
dc.contributor.authorKettunen, Johannesen_US
dc.contributor.authorWaldenberger, Melanieen_US
dc.date.accessioned2021-01-28T07:51:11Z-
dc.date.available2021-01-28T07:51:11Z-
dc.date.issued2021-
dc.identifier.citationGomez-Alonso, M. C., Kretschmer, A., Wilson, R., Pfeifer, L., Karhunen, V., Seppälä, I., . . . Waldenberger, M. (2021). DNA methylation and lipid metabolism : an EWAS of 226 metabolic measures. Clinical Epigenetics, 13(1), 7-. doi:10.1186/s13148-020-00957-8en_US
dc.identifier.issn1868-7075en_US
dc.identifier.other0000-0003-0583-5093-
dc.identifier.urihttps://hdl.handle.net/10356/146162-
dc.description.abstractBackground: The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results: We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion: Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.en_US
dc.language.isoenen_US
dc.relation.ispartofClinical Epigeneticsen_US
dc.rights© 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.en_US
dc.subjectScience::Medicineen_US
dc.titleDNA methylation and lipid metabolism : an EWAS of 226 metabolic measuresen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.identifier.doi10.1186/s13148-020-00957-8-
dc.description.versionPublished versionen_US
dc.identifier.pmid33413638-
dc.identifier.scopus2-s2.0-85098891467-
dc.identifier.issue1en_US
dc.identifier.volume13en_US
dc.subject.keywordsCpG Siteen_US
dc.subject.keywordsVLDLen_US
item.grantfulltextopen-
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