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 note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 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