DNA methylation and its relationship with lifestyle, environmental and cardiovascular risk factors

Coronary artery disease is the first cause of death worldwide, and as a complex disease implies the interplay between genetic and environmental factors. Common genetic variants explain only 15-20% of its heritability. DNA methylation, which regulates the gene expression without altering the DNA sequence, has been proposed as a heritable signature to explain this missing heritability and as a mediator effect of lifestyle and environment on health. To study the relationship between DNA methylation and smoking, air pollution, and cardiovascular risk factors (obesity, lipid profile, and HDL functionality) we used epigenome-wide association studies, Mendelian randomization, and multi-stage omics integration approaches. We included data from ten studies, but the results were mainly based on the REGICOR (REgistre GIroni del COR) cohort. We report the association between smoking and 63 methylation sites (CpGs). We did not find association between air pollution and DNA methylation. We identified 94 CpGs associated with obesity and 14 with lipid profile. We observed that methylation at CPT1A and SLC7A11 can modify or be affected by the triglycerides levels, highlighting the complexity of the lipids homeostasis. Finally, we performed the first study showing an association between DNA methylation and HDL functionality. As conclusions of this research, smoking is strongly associated with a distinctive methylation pattern and there is a relationship between DNA methylation and several cardiovascular risk factors, although its causality is complex.