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

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

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

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.C.L. was supported by a fellowship from "la Caixa" Foundation (ID 100010434) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 847 648. The fellowship code is LCF/BQ/PR21/11840003. The REGICOR study was funded by the Carlos III Health Institute and European Regional Development Fund (FIS PI12/00232; FIS PI15/00051, CIBERCV, CIBERESP) and the Government of Catalonia through the Agency for Management of University and Research Grants (AGAUR: PERIS SLT002/16/00088, 2017SGR222). A.F.-S. was supported by the British Heart Foundation (AA/18/1/34219) and the Medical Research Council (UK MRC) (MC_UU_00011/6). O.R. was supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). The Framingham Heart Study (FHS) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (contract no. N01-HC-25195 and HHSN268201500001I). The Women’s Health Initiative (WHI) programme is funded by the NHLBI (contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221). This manuscript was not prepared in collaboration with investigators of the FHS/WHI, has not been reviewed and/or approved by the FHS/WHI, and does not necessarily reflect the opinions or views of the FHS and WHI investigators or the NHLBI. The funding bodies had no role in the study design, collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication