DNA methylation biomarkers of myocardial infarction and cardiovascular disease

  • Clin Epigenetics. 2021 Apr 21;13(1):86. doi: 10.1186/s13148-021-01078-6.
Alba Fernández-Sanlés  1  2  3 ,  Sergi Sayols-Baixeras  1  4  5 ,  Isaac Subirana  1  6 ,  Mariano Sentí  2 ,  S Pérez-Fernández  1  4 ,  Manuel de Castro Moura  7 ,  Manel Esteller  7  8  9  10 ,  Jaume Marrugat  1  4 ,  Roberto Elosua  11  12  13
Affiliations
  • 1. Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003, Barcelona, Catalonia, Spain.
  • 2. Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain.
  • 3. Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • 4. CIBER Cardiovascular Diseases (CIBERCV), Madrid, Spain.
  • 5. Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
  • 6. CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
  • 7. Josep Carreras Leukaemia Research Institute (IJC), Badalona, Catalonia, Spain.
  • 8. CIBER Oncology (CIBERONC), Madrid, Spain.
  • 9. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Catalonia, Spain.
  • 10. Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain.
  • 11. Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003, Barcelona, Catalonia, Spain. [email protected].
  • 12. CIBER Cardiovascular Diseases (CIBERCV), Madrid, Spain. [email protected].
  • 13. Medicine Department, Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain. [email protected].
PMID: 33883000 DOI: 10.1186/s13148-021-01078-6
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.

Keywords
Cardiovascular disease; DNA methylation; Epigenome-wide association study; Myocardial infarction; Predictive biomarkers.