eprintid: 10167406
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/16/74/06
datestamp: 2023-03-29 13:59:10
lastmod: 2023-03-29 13:59:10
status_changed: 2023-03-29 13:59:10
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Fernandez-Sanles, Alba
title: DNA methylation biomarkers of myocardial infarction and cardiovascular disease
ispublished: pub
divisions: UCL
divisions: B02
divisions: D14
divisions: GA3
divisions: G17
keywords: Science & Technology, Life Sciences & Biomedicine, Oncology, Genetics & Heredity, DNA methylation, Epigenome-wide association study, Predictive biomarkers, Myocardial infarction, Cardiovascular disease, CORONARY-HEART-DISEASE, WIDE ASSOCIATION, CPG SITES, GENETIC INFLUENCES, RISK, IDENTIFICATION, VALIDATION, MICROARRAY
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abstract: Background: The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylated loci associated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers. Results: We designed a case–control, two-stage, epigenome-wide association study on AMI (ndiscovery = 391, nvalidation = 204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. We performed a fixed-effects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n ~ 1800 and n ~ 2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infinium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic influence and therefore the results were not conclusive. Conclusions: We have identified 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.
date: 2021-04-21
date_type: published
publisher: BioMed Central
official_url: https://doi.org/10.1186/s13148-021-01078-6
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2011099
doi: 10.1186/s13148-021-01078-6
medium: Electronic
pii: 10.1186/s13148-021-01078-6
lyricists_name: Fernandez-Sanles, Alba
lyricists_id: AFERA98
actors_name: Fernandez-Sanles, Alba
actors_id: AFERA98
actors_role: owner
funding_acknowledgements: FIS PI18/00017 [Carlos III Health Institute-European Regional Development Fund]; FIS PI15/00051 [Carlos III Health Institute-European Regional Development Fund]; PI12/00232 [Carlos III Health Institute-European Regional Development Fund]; SLT002/16/00088 [PERIS from Agencia de Gestio d'Ajuts Universitaris i de Recerca]; 2014SGR240 [Government of Catalonia through the Agency for Management of University and Research Grants]; 2017SGR946 [Government of Catalonia through the Agency for Management of University and Research Grants]; BES-2014-069718 [Spanish Ministry of Economy and Competitiveness]; IFI14/00007 [Carlos III Health Institute-FEDER]; [National Heart, Lung, and Blood Institute (NHLBI)]; N01-HC-25195 [Boston University]; HHSN268201500001I [Boston University]; N01WH22110 [NHLBI]; 24152 [NHLBI]; 32100-2 [NHLBI]; 32105-6 [NHLBI]; 32108-9 [NHLBI]; 32111-13 [NHLBI]; 32115 [NHLBI]; 32118-32119 [NHLBI]; 32122 [NHLBI]; 42107-26 [NHLBI]; 42129-32 [NHLBI]; 44221 [NHLBI]
full_text_status: public
publication: Clinical Epigenetics
volume: 13
number: 1
article_number: 86
pages: 11
event_location: Germany
citation:        Fernandez-Sanles, Alba;      (2021)    DNA methylation biomarkers of myocardial infarction and cardiovascular disease.                   Clinical Epigenetics , 13  (1)    , Article 86.  10.1186/s13148-021-01078-6 <https://doi.org/10.1186/s13148-021-01078-6>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10167406/1/DNA%20methylation%20biomarkers%20of%20myocardial%20infarction%20and%20cardiovascular%20disease.pdf