Dietary induced methylome and transcriptome dynamics assessing nutrition impacts on cardiovascular and metabolic health
|Partner Organization||Partner Country|
|Helmholtz Zentrum München||Germany|
|Leiden University Medical Center||The Netherlands|
|INSERM U974 Center of Research in Myology||France|
|Ludwig-Maximilians-Universität (LMU) München||Germany|
1. Overall project description
Cardiovascular and metabolic diseases are a primary cause of morbidity and mortality worldwide. Diet is a major risk factor for cardio-metabolic health, but is challenging to study in part because metabolic response to diet is highly individualised. Characterising the molecular pathways that mediate personalised responses to diet is critical to effectively tackle the current epidemic. Epigenetic mechanisms are key regulators of gene function that can change in response to external stimuli, including diet.
The DIMENSION consortium investigates dynamically the causal impacts of dietary intake on epigenetic regulation of gene function across tissues, and their impact on subsequent cardio-metabolic health outcomes. The work programme is based on (i) targeted postprandial and nutritional intervention studies to tackle the causal relationships between diet, epigenetic modifications and gene function, in combination with (ii) state-of-the-art analyses to characterize the links between diet, epigenetics, and cardio-metabolic health using novel diet measures including metabolomics in extensively studied cohorts, and (iii) functional follow-up experiments assessing the impact of diet-induced epigenetic and transcriptomic signals at the level of cells, within and across tissues.
The DIMENSION consortium aims to deliver novel mechanistic insights into how exactly nutritional modifications can modulate the regulatory and functional genome to promote cardio-metabolic health. These insights will complement traditional population-based guidelines and have potential impacts to inform the rapidly evolving area of individualised nutrition-based strategies.
Preliminary results from initial analyses within DIMENSION consortium datasets have contributed towards identifying biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D, and towards identifying epigenetic signatures of dietary intakes, which have been presented at an international conference in November 2019. DNAmArray, a workflow for preprocessing and quality control of DNA methylation data, has been streamlined and documentation can be accessed here. Analysis of dietary-induced dynamic epigenetic and transcriptional profiles, and further dietary and cardio-metabolic health population-based epigenomic analyses are underway.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Partners Number||Doi|
|Liu J, Carnero-Montoro E, ... 52 authors..., Bell JT*, Demirkan A, and van Duijn CM.||An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis||https://doi.org/10.1038/s41467-019-10487-4||Download|
|Le Roy CI, Bowyer RCE, Castillo-Fernandez JE, Pallister T, Menni C, Steves CJ, Berry SE*, Spector TD, and Bell JT*||Dissecting the role of the gut microbiota and diet on visceral fat mass accumulation||https://doi.org/10.1038/s41598-019-46193-w||Download|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|