Nutrition and cardiometabolic health: the role of DNA methylation

The overall aim of this thesis was to investigate associations between nutritional factors, DNA methylation, and cardiometabolic health in children as well as adults. (Figure 1.1.). Therefore, the following objectives were: 1. To investigate nutritional factors associated with DNA methylation. 2. To identify differentially methylated CpG sites in relation to cardiometabolic risk factors. 3. To examine associations between nutrition and cardiometabolic risk factors in childhood. 4. To examine associations between nutrition and cardiometabolic diseases in adulthood

Carbohydrate Intake in Early Childhood and Body Composition and Metabolic Health: Results from the Generation R Study

High sugar intake in childhood has been linked to obesity. However, the role of macronutrient substitutions and associations with metabolic health remain unclear. We examined associations of carbohydrate intake and its subtypes with body composition and metabolic health among 3573 children participating in a population-based cohort in the Netherlands. Intake of total carbohydrate, monosaccharides and disaccharides, and polysaccharides at age 1 year was assessed with a food-frequency questionnaire. We repeatedly measured children’s height and weight to calculate BMI between their ages of 1 and 10 years. At ages 6 and 10 years, fat and fat-free mass were measured with dual-energy X-ray-absorptiometry and blood concentrations of triglycerides, cholesterol, and insulin were obtained. For all outcomes, we calculated age and sexspecific SD-scores. In multivariable-adjusted linear mixed models, we found no associations of intake of carbohydrates or its subtypes with children’s BMI or body composition. A higher intake of monosaccharides and disaccharides was associated with higher triglyceride concentrations (0.02 SDS per 10 g/day, 95% CI: 0.01, 0.04). Higher monosaccharide and disaccharide intake was also associated with lower HDL-cholesterol (−0.03 SDS, 95% CI: −0.04; −0.01), especially when it replaced polysaccharides. Overall, our findings suggest associations of higher monosaccharide and disaccharide intake in early childhood with higher triglyceride and lower HDL-choleste

Associations between Dietary Fiber Intake in Infancy and Cardiometabolic Health at School Age: The Generation R Study

Dietary fiber (DF) intake may be beneficial for cardiometabolic health. However, whether this already occurs in early childhood is unclear. We investigated associations between DF intake in infancy and cardiometabolic health in childhood among 2032 children participating in a population-based cohort in The Netherlands. Information on DF intake at a median age of 12.9 months was collected using a food-frequency questionnaire. DF was adjusted for energy intake using the residual method. At age 6 years, body fat percentage, high-density lipoprotein (HDL)-cholesterol, insulin, triglycerides, and blood pressure were assessed and expressed in age- and sex-specific standard deviation scores (SDS). These five factors were combined into a cardiometabolic risk factor score. In models adjusted for several parental and child cova

Associations of Activity and Sleep With Quality of Life: A Compositional Data Analysis

Introduction: Associations between time spent on physical activity, sedentary behavior, and sleep and quality of life are usually studied without considering that their combined time is fixed. This study investigates the reallocation of time spent on physical activity, sedentary behavior, and sleep during the 24-hour day and their associations with quality of life. Methods: Data from the 2011–2016 Rotterdam Study were used to perform this cross-sectional analysis among 1,934 participants aged 51–94 years. Time spent in activity levels (sedentary, light-intensity physical activity, moderate-to-vigorous physical activity, and sleep) were objectively measured with a wrist-worn accelerometer combined with a sleep diary. Quality of life was measured using the EuroQoL 5D-3L questionnaire. The compositional isotemporal substitution method was used in 2018 to examine the association between the distribution of time spent in different activity behaviors and quality of life. Results: Reallocation of 30 minutes from sedentary behavior, light-intensity physical activity, or sleep to moderate-to-vigorous physical activity was associated with a higher quality of life, whereas reallocation from moderate-to-vigorous physical activity to sedentary behavior, light-intensity physical activity, or sleep was associated with lower quality of life. To illustrate this, a reallocation of 30 minutes from sedentary behavior to moderate-to-vigorous physical activity was associated with a 3% (95% CI=2, 4) higher quality of life score. By contrast, a reallocation of 30 minutes from moderate-to-vigorous physical activity to sedentary behavior was associated with a 4% (95% CI=2, 6) lower quality of life score. Conclusions: Moderate-to-vigorous physical activity is important with regard to the quality of life of middle-aged and elderly individuals. The benefits of preventing less time spent in moderate-to-vigorous physical activity were greater than the benefits of more time spent in moderate-to-vigorous physical activity. These results could shift the attention to interventions focused on preventing reductions in moderate-to-vigorous physical activity levels. Further longitudinal studies are needed to confirm these findings and explore causality

Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review

Sex is a major determinant of cardiometabolic risk. DNA methylation (DNAm), an important epigenetic mechanism that differs between sexes, has been associated with cardiometabolic diseases. Therefore, we aimed to systematically review studies in adults investigating sex-specific associations of DNAm with intermediate cardiometabolic traits and incident cardiovascular disease including stroke, myocardial infarction (MI) and coronary heart disease (CHD). Five bibliographic databases were searched from inception to 15 July 2019. We selected 35 articles (based on 30 unique studies) from 17,023 references identified, with a total of 14,020 participants of European, North American or Asian ancestry. Four studies reported sex differences between global DNAm and blood lipid levels and stroke risk. In 25 studies that took a genome wide or candidate gene approach, DNAm at 31 gene sites was associated with sex differences in cardiometabolic diseases. The identified genes were PLA2G7, BCL11A, KDM6A, LIPC, ABCG1, PLTP, CETP, ADD1, CNN1B, HOOK2, GFBP-7,PTPN1, GCK, PTX3, ABCG1, GALNT2, CDKN2B, APOE, CTH, GNASAS, INS, PON1, TCN2, CBS, AMT, KDMA6A, FTO, MAP3K13, CCDC8, MMP-2 and ER-α. Prioritized pathway connectivity analysis associated these genes with biological pathways such as vitamin B12 metabolism, statin pathway, plasma lipoprotein, plasma lipoprotein assembly, remodeling and clearance and cholesterol metabolism. Our findings suggest that DNAm might be a promising molecular strategy for understanding sex differences in the pathophysiology of cardiometabolic diseases and that future studies should investigate the effects of sex on epigenetic mechanisms in cardiometabolic risk. In addition, we emphasize the gap between the translational potential and the clinical utilization of cardiometabolic epigenetics

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction

Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value &lt;1.1×10−7), which annotated to the AHRR, F2RL3, FLJ43663

Publisher Correction

The original version of this Article contained an error in the spelling of the author Min-A Jhun which was incorrectly given as Mina-A Jhun. This has now been corrected in both the PDF and HTML versions of the Article.</p