Aims: Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aims were to identify cytosine-phosphate-guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm) and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D), and coronary heart disease (CHD).
Methods and results: Meta-EWAS including 5274 participants in four cohorts from Spain, the USA, and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet, to a healthy plant-based diet, and to the Dietary Approaches to Stop Hypertension. Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits. We found 18 differentially methylated CpGs associated with dietary scores (P < 1.08 × 10-7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI and at cg05399785 (WDR8) with greater SBP, and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk, and CHD risk and at cg0557921 (AHRR) with lower CHD risk.
Conclusion: Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.
Keywords: Cardiovascular disease; DNA methylation; Diet quality; Epidemiology; Nutrition.
We conducted a study to investigate the connection between diet quality, epigenetic changes, and cardiovascular health in adults. The study included 5274 participants from Spain, the USA, and the UK, combining data from four different cohorts. We assessed adherence to different healthy diets: Mediterranean style diet, plant-based diet, and Dietary Approaches to Stop Hypertension diet. We used advanced technology to analyse blood DNA methylation, which refers to chemical modifications in the DNA that can affect gene activity.We discovered 18 CpGs that showed differential methylation patterns related to the dietary scores. Importantly, 12 of these CpGs had previously been associated with cardiovascular disease or risk factors, suggesting a potential link between diet, epigenetic changes, and heart health. Some of the diet-related CpGs mapped to genes involved in pathways associated with cardiovascular disease. Moreover, using a method called Mendelian randomization, we found that several CpGs may have a causal association with body mass index, systolic blood pressure, and risk of type 2 diabetes and coronary heart disease.
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.