DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures.
CpG site
Fatty acids
HDL
LDL
Lipoprotein composition
Lipoprotein sizes
Myocardial infarction
NMR
Obesity
VLDL
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
07 01 2021
07 01 2021
Historique:
received:
25
08
2020
accepted:
22
10
2020
entrez:
8
1
2021
pubmed:
9
1
2021
medline:
15
12
2021
Statut:
epublish
Résumé
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. 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 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.
Sections du résumé
BACKGROUND
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
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.
Identifiants
pubmed: 33413638
doi: 10.1186/s13148-020-00957-8
pii: 10.1186/s13148-020-00957-8
pmc: PMC7789600
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7Subventions
Organisme : Welcome Trust
ID : 084723/Z/08/Z
Organisme : British Heart Foundation
ID : SP/04/002
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700931
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098381
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S019669/1
Pays : United Kingdom
Organisme : Department of Health
ID : RP-PG-0407-10371
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0601966
Pays : United Kingdom
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