Blood DNA methylation signature of diet quality and association with cardiometabolic traits

Abstract

Background Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aim was 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 Meta-EWAS including 5,274 participants in four cohorts from Spain, the US and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet (MMDS), to a healthy plant-based diet (HPDI) and to the Dietary Approaches to Stop Hypertension (DASH). Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450 K 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. Results We found 18 differentially methylated CpGs associated with dietary scores (p-value < 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. Conclusions Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health. Availability: The R code for the analysis is available in the following Github repository: https://github.com/jorgedb98/B64_DIAMETR.git

Epigenetic modifications in obesity‐associated diseases

“…210 Improved diet quality can alter the levels of DNAm in cardiometabolism-related genes, which is linked with increased risk of hypertension and CHDs. 239 Energy restriction has always been the main intervention for weight loss, but it poses significant challenges to long-term dietary intervention due to its impact on health and low compliance. Certain nutrients are thought to mitigate the impact of obesity, and their proper intake may help prevent obesity-associated diseases.…”

“…In addition, dietary intervention for individuals in early T2D has the potential to mitigate the impairment on β cells due to lipotoxicity and inflammation by reinstating the chromatin reprogramming 210 . Improved diet quality can alter the levels of DNAm in cardiometabolism‐related genes, which is linked with increased risk of hypertension and CHDs 239 . Energy restriction has always been the main intervention for weight loss, but it poses significant challenges to long‐term dietary intervention due to its impact on health and low compliance.…”