Fine-grained investigation of the relationship between human nutrition and global DNA methylation patterns

Abstract

Purpose: Nutrition is an important, modifiable, environmental factor affecting human health by modulating epigenetic processes, including DNA methylation (5mC).Numerous studies investigated the association of nutrition with global and genespecific DNA methylation and evidences on animal models highlighted a role in DNA hydroxymethylation (5hmC) regulation. However, a more comprehensive analysis of different layers of nutrition in association with global levels of 5mC and 5hmC is lacking. We investigated the association between global levels of 5mC and 5hmC and human nutrition, through the stratification and analysis of dietary patterns into different nutritional layers: adherence to Mediterranean Diet (MD), main food groups, macronutrients and micronutrients intake. Methods:ELISA technique was used to measure global 5mC and 5hmC levels in 1,080 subjects from the Moli-sani cohort. Food intake during the 12 months before enrolment was assessed by using the semi-quantitative EPIC food frequency questionnaire. Complementary approaches involving both classical statistics and supervised machine learning analyses were used to investigate the associations between global 5mC and 5hmC levels and adherence to Mediterranean diet, main food groups, macronutrients and micronutrients intake. Results:We found that global DNA methylation, but not hydroxymethylation, was associated with daily intake of zinc and vitamin B3. Random Forests algorithms predicting 5mC and 5hmC through intakes of food groups, macronutrients and micronutrients revealed a significant contribution of zinc, while vitamin B3 was reported among the most influential features. 6 Conclusion: We found that nutrition may affect global DNA methylation, suggesting a contribution of micronutrients previously implicated as cofactors in methylation pathways.

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS

“…So far, some analyses on the link between diet and global DNA methylation patterns [ 7 ], as well as diet and site-specific epigenetic changes [ 3 ], have been performed. In terms of site-specific analysis, the main focus of nutri-epigenomic research has been on epigenome-wide association studies (EWAS) of nutrients involved in human C1 metabolism [ 3 , 4 ].…”

Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort

“…The characteristics of the analyzed sub-cohort ( N = 1080 with at least an epigenetic measure available) are summarized elsewhere [ 23 ] and in Table 1 . Compared to the whole Moli-sani cohort, the population under study showed similar sex ratio (48.0% vs 48.1% men) but slightly lower age (mean (SD) age 54.9 (11.5) year vs 55.8 (12.0) years, p < 0.0001), due to the removal of prevalent CVD cases.…”

“…The study population was already described in Noro et al [ 23 ] and composed of a randomly selected sub-cohort of 1,160 participants of the Moli-sani study ( N = 24,325; 49.20% men; age ≥ 35 years, recruited between 2005 and 2010) [ 53 , 54 ]. Subjects with incomplete dietary questionnaires or with missing values in the studied variables were excluded from the analysis to a final number of 1080 subjects.…”

“…We overall measured 5mC and 5hmC global levels for 1214 samples (including 1,140 original and 74 duplicate samples). Of these, samples with absorbance optical density (OD) values below the mean of negative controls plus 2 standard deviations (SDs) for both global methylation measurements were set to missing as described [ 23 ]. We additionally excluded: (1) 17 and 2 outlier samples for 5mC and 5hmC, respectively, defined as samples with absolute values of standardized methylation levels above 3 standard deviations; and (2) all prevalent CVD cases (56 and 58 samples for 5mC and 5hmC, respectively) to exclude reverse causality of CVD on methylation levels [ 56 ].…”

“…In the present study, we aimed at investigating the associations between both GI and GL and global DNA methylation within an Italian population cohort enrolled in the Moli-sani study. We already reported a fine-grained analysis of global DNA methylation patterns at different nutritional levels in the same cohort, identifying a direct relationship between daily intake of zinc and global DNA methylation [ 23 ]. Here, we focused on dietary glycaemic indices to build a bridge with altered epigenetic patterns potentially underlying metabolic conditions.…”