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

Author:

Domínguez-Barragán Jorge1,Fernández-Sanlés Alba23,Hernáez Álvaro456ORCID,Llauradó-Pont Joana7ORCID,Marrugat Jaume18ORCID,Robinson Oliver9ORCID,Tzoulaki Ioanna1011ORCID,Elosua Roberto1812ORCID,Lassale Camille16713ORCID

Affiliation:

1. Hospital del Mar Research Institute (IMIM) , Programme of Epidemiology and Public Health, Dr Aiguader, 88, 08003 Barcelona , Spain

2. MRC Unit for Lifelong Health and Ageing, University College London , London WC1E 7HB , UK

3. Population Health Sciences, Bristol Medical School, University of Bristol , Bristol BS8 2BN , UK

4. Centre for Fertility and Health, Norwegian Institute of Public Health , Oslo 0463 , Norway

5. Blanquerna School of Health Sciences, Universitat Ramon Llull , 08025 Barcelona , Spain

6. Consortium for Biomedical Research—Pathophysiology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III , Monforte de Lemos 3-5, 08029 Madrid , Spain

7. Barcelona Institute of Global Health (ISGlobal) , Dr Aiguader 88, 08003, Barcelona , Spain

8. Consortium for Biomedical Research—Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III , Madrid , Spain

9. μedical Research Council Centre for Environment and Health, School of Public Health, Imperial College London , London W2 1PG , UK

10. Centre for Systems Biology, Biomedical Research Foundation of the Academy of Athens , 115 27 Athens , Greece

11. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London , London W2 1PG , UK

12. Faculty of Medicine, University of Vic—Central University of Catalunya , Ctra. de Roda, 70, 08500 Vic , Spain

13. Universitat Pompeu Fabra (UPF) , Dr Aiguader 88, 08003, Barcelona , Spain

Abstract

Abstract 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.

Funder

‘La Caixa’ Foundation

Carlos III Health Institute–European Regional Development Fund

Government of Catalonia through the Agency for Management of University

Bristol British Heart Foundation Accelerator Award

UK Medical Research Council

Integrative Epidemiology Unit at the University of Bristol

UKRI Future Leaders Fellowship

The Framingham Heart Study

National Heart, Lung, and Blood Institute

The Women’s Health Initiative

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Epidemiology

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Epigenetic modifications in obesity‐associated diseases;MedComm;2024-02

2. Editorial comment: focus on risk prediction and assessment;European Journal of Preventive Cardiology;2024-01

3. The epigenome, the missing link between diet and cardiovascular disease?;European Journal of Preventive Cardiology;2023-10-05

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