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Epigenome-wide association study of dietary fatty acid intake.
Lange de Luna, J, Nounu, A, Neumeyer, S, Sinke, L, Wilson, R, Hellbach, F, Matías-García, PR, Delerue, T, Winkelmann, J, Peters, A, et al
Clinical epigenetics. 2024;(1):29
Abstract
BACKGROUND Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS). RESULTS DNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10-8), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10-5, 95%CI: 1.28 × 10-5-2.73 × 10-5, P value: 6.98 × 10-8), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10-5, 95%CI: 6.25 × 10-5-1.33 × 10-4, P value: 6.75 × 10-8). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10-7) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10-5, 95% CI: 1.27 × 10-5-2.73 × 10-5, P value = 5.99 × 10-8) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10-5, 95% CI: 1.31 × 10-5-2.83 × 10-5, P value = 1.00 × 10-7 and beta: 2.19 × 10-5, 95% CI: 1.41 × 10-5-2.97 × 10-5, P value = 5.91 × 10-8 respectively). CONCLUSIONS Our study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.
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Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.
Hellbach, F, Sinke, L, Costeira, R, Baumeister, SE, Beekman, M, Louca, P, Leeming, ER, Mompeo, O, Berry, S, Wilson, R, et al
European journal of nutrition. 2023;(3):1357-1375
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Abstract
PURPOSE Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.
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Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.
Keshawarz, A, Joehanes, R, Ma, J, Lee, GY, Costeira, R, Tsai, PC, Masachs, OM, Bell, JT, Wilson, R, Thorand, B, et al
Epigenetics. 2023;(1):2211361
Abstract
BACKGROUND Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.
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Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry.
Schmitz, T, Thilo, C, Linseisen, J, Heier, M, Peters, A, Kuch, B, Meisinger, C
Scientific reports. 2021;(1):2476
Abstract
Calcium plays an essential role in physiology of the cardiovascular system. Aberrations from normal serum calcium levels are known to be associated with several cardiovascular diseases. Its possible role as a predictor for long-term mortality after acute myocardial infarction (AMI) is still uncertain. In this study, a total of 3732 patients (aged 25-74 years) with incident AMI surviving at least 28 days after AMI was included. The median follow-up time was 6.0 years. Admission total serum calcium levels were divided into quartiles. The Kaplan-Meier-Curve suggested a division of the follow up time in two different time periods. So, Cox regression models were calculated to assess association between admission serum calcium levels and all-cause long-term mortality with two observation periods: 28-2500 days and > 2500 days. The final model was adjusted for various comorbidities, clinical characteristics, in-hospital treatment and medication. The third quartile (normal-high Calcium levels) served as the reference group. The fully adjusted Cox-regression model shows significantly higher mortality risk for low serum calcium (quartile 1) within the timeframe 28-2500 days after the event (OR 1.53 [1.19-1.98]). The other groups did not differ significantly from each other. In the later observation period (from 2500 days until death or censoring) no more significant differences were seen between the four calcium quartiles. In summary, low serum calcium is an independent predictor of adverse outcome in the first 2500 days (about 7 years) after AMI. On later points in time this effect attenuates, so that no more significant differences can be observed.
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Significant Impact of Coffee Consumption on MR-Based Measures of Cardiac Function in a Population-Based Cohort Study without Manifest Cardiovascular Disease.
Beller, E, Lorbeer, R, Keeser, D, Galiè, F, Meinel, FG, Grosu, S, Bamberg, F, Storz, C, Schlett, CL, Peters, A, et al
Nutrients. 2021;(4)
Abstract
Subclinical effects of coffee consumption (CC) with regard to metabolic, cardiac, and neurological complications were evaluated using a whole-body magnetic resonance imaging (MRI) protocol. A blended approach was used to estimate habitual CC in a population-based study cohort without a history of cardiovascular disease. Associations of CC with MRI markers of gray matter volume, white matter hyperintensities, cerebral microhemorrhages, total and visceral adipose tissue (VAT), hepatic proton density fat fraction, early/late diastolic filling rate, end-diastolic/-systolic and stroke volume, ejection fraction, peak ejection rate, and myocardial mass were evaluated by linear regression. In our analysis with 132 women and 168 men, CC was positively associated with MR-based cardiac function parameters including late diastolic filling rate, stroke volume (p < 0.01 each), and ejection fraction (p < 0.05) when adjusting for age, sex, smoking, hypertension, diabetes, Low-density lipoprotein (LDL), triglycerides, cholesterol, and alcohol consumption. CC was inversely associated with VAT independent of demographic variables and cardiovascular risk factors (p < 0.05), but this association did not remain significant after additional adjustment for alcohol consumption. CC was not significantly associated with potential neurodegeneration. We found a significant positive and independent association between CC and MRI-based systolic and diastolic cardiac function. CC was also inversely associated with VAT but not independent of alcohol consumption.
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Association between dietary patterns and prediabetes, undetected diabetes or clinically diagnosed diabetes: results from the KORA FF4 study.
Pestoni, G, Riedl, A, Breuninger, TA, Wawro, N, Krieger, JP, Meisinger, C, Rathmann, W, Thorand, B, Harris, C, Peters, A, et al
European journal of nutrition. 2021;(5):2331-2341
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PURPOSE Diet is one of the most important modifiable risk factors for the development of type 2 diabetes. Here, we aim to identify dietary patterns and to investigate their association with prediabetes, undetected diabetes and prevalent diabetes. METHODS The present study included 1305 participants of the cross-sectional population-based KORA FF4 study. Oral glucose tolerance test (OGTT) measurements together with a physician-confirmed diagnosis allowed for an accurate categorization of the participants according to their glucose tolerance status into normal glucose tolerance (n = 698), prediabetes (n = 459), undetected diabetes (n = 49), and prevalent diabetes (n = 99). Dietary patterns were identified through principal component analysis followed by hierarchical clustering. The association between dietary patterns and glucose tolerance status was investigated using multinomial logistic regression models. RESULTS A Prudent pattern, characterized by high consumption of vegetables, fruits, wholegrains and dairy products, and a Western pattern, characterized by high consumption of red and processed meat, alcoholic beverages, refined grains and sugar-sweetened beverages, were identified. Participants following the Western pattern had significantly higher chances of having prediabetes (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.35, 2.73), undetected diabetes (OR 10.12; 95% CI 4.19, 24.43) or prevalent diabetes (OR 3.51; 95% CI 1.85, 6.67), compared to participants following the Prudent pattern. CONCLUSION To our knowledge, the present study is one of the few investigating the association between dietary patterns and prediabetes or undetected diabetes. The use of a reference group exclusively including participants with normal glucose tolerance might explain the strong associations observed in our study. These results suggest a very important role of dietary habits in the prevention of prediabetes and type 2 diabetes.
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Revised D-A-CH Reference Values for the Intake of Vitamin B6.
Jungert, A, Linseisen, J, Wagner, KH, Richter, M, ,
Annals of nutrition & metabolism. 2020;(4):213-222
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BACKGROUND The Nutrition Societies of Germany, Austria, and Switzerland as the joint editors of the "D-A-CH reference values for nutrient intake" have revised the reference values for vitamin B6 in summer 2019. SUMMARY For women, the average requirement (AR) for vitamin B6 intake was derived on the basis of balance studies using a pyridoxal-5'-phosphate (PLP) plasma concentration of ≥30 nmol/L as a biomarker of an adequate vitamin B6 status. The recommended intake (RI) was derived considering a coefficient of variation of 10%. The RIs of vitamin B6 for men, children, and adolescents were extrapolated from the vitamin B6 requirement for women considering differences in body weight, an allometric exponent, growth factors as appropriate, and a coefficient of variation. For infants aged 0 to under 4 months, an estimated value was set based on the vitamin B6 intake via breast feeding. The reference value for infants aged 4 to under 12 months was extrapolated from the estimated value for infants under 4 months of age and the average vitamin B6 requirement for adults. The reference values for pregnant and lactating women consider the requirements for the foetus and the loss via breast milk. Key Messages: According to the combined analysis of 5 balance studies, the AR for vitamin B6 to ensure a plasma PLP concentration of ≥30 nmol/L is 1.2 mg/day for adult females and the extrapolated AR for adult males is 1.3 mg/day. The corresponding RIs of vitamin B6 are 1.4 mg/day for adult females and 1.6 mg/day for adult males, independent of age. For infants, the estimated value is 0.1 mg/day and 0.3 mg/day, depending on age. The AR of vitamin B6 for children and adolescents ranges between 0.5 and 1.5 mg/day, and the RI is between 0.6 mg/day and 1.6 mg/day. During pregnancy, the AR is 1.3 mg/day in the first trimester and 1.5 mg/day in the second and third trimesters; the RI is 1.5 mg/day in the first trimester and 1.8 mg/day in the second and third trimesters. For lactating women, the AR is 1.3 mg/day and the RI is 1.6 mg/day.
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Revised D-A-CH-reference values for the intake of zinc.
Haase, H, Ellinger, S, Linseisen, J, Neuhäuser-Berthold, M, Richter, M, ,
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2020;:126536
Abstract
BACKGROUND The Nutrition Societies of Germany, Austria and Switzerland as the joint editors of the 'D-A-CH reference values for nutrient intake' have revised the reference values for zinc in July 2019. METHODS For infants aged 0 to under 4 months, an estimated value was set based on the zinc intake via breast feeding. For all other age groups, the reference values were calculated using the factorial method considering endogenous zinc losses via intestinal losses, urine, faeces, skin and sweat, semen in men and the additional zinc requirements to build up body weight in children and adolescents as well as in pregnant women. Due to the strong influence of phytate intake on zinc absorption, the recommendations for the intake of zinc for adults are derived depending on low (0.5 mmol/day, corresponding to 330 mg/day), moderate (1.0 mmol/day, corresponding to 660 mg/day) and high (1.5 mmol/day, corresponding to 990 mg/day) phytate intake. The reference values for lactating women take into account the zinc loss via breast milk. RESULTS AND CONCLUSION For adults, pregnant and lactating women, the recommended intake values for zinc range from 7 mg/day to 16 mg/day, depending on sex and dietary phytate intake.
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Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review.
Maretzke, F, Bechthold, A, Egert, S, Ernst, JB, Melo van Lent, D, Pilz, S, Reichrath, J, Stangl, GI, Stehle, P, Volkert, D, et al
Nutrients. 2020;(4)
Abstract
Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.
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Arrhythmic Gut Microbiome Signatures Predict Risk of Type 2 Diabetes.
Reitmeier, S, Kiessling, S, Clavel, T, List, M, Almeida, EL, Ghosh, TS, Neuhaus, K, Grallert, H, Linseisen, J, Skurk, T, et al
Cell host & microbe. 2020;(2):258-272.e6
Abstract
Lifestyle, obesity, and the gut microbiome are important risk factors for metabolic disorders. We demonstrate in 1,976 subjects of a German population cohort (KORA) that specific microbiota members show 24-h oscillations in their relative abundance and identified 13 taxa with disrupted rhythmicity in type 2 diabetes (T2D). Cross-validated prediction models based on this signature similarly classified T2D. In an independent cohort (FoCus), disruption of microbial oscillation and the model for T2D classification was confirmed in 1,363 subjects. This arrhythmic risk signature was able to predict T2D in 699 KORA subjects 5 years after initial sampling, being most effective in combination with BMI. Shotgun metagenomic analysis functionally linked 26 metabolic pathways to the diurnal oscillation of gut bacteria. Thus, a cohort-specific risk pattern of arrhythmic taxa enables classification and prediction of T2D, suggesting a functional link between circadian rhythms and the microbiome in metabolic diseases.