Association between Usual Dietary Intake of Food Groups and DNA Methylation and Effect Modification by Metabotype in the KORA FF4 Cohort

Abstract

Associations between diet and DNA methylation may vary among subjects with different metabolic states, which can be captured by clustering populations in metabolically homogenous subgroups, called metabotypes. Our aim was to examine the relationship between habitual consumption of various food groups and DNA methylation as well as to test for effect modification by metabotype. A cross-sectional analysis of participants (median age 58 years) of the population-based prospective KORA FF4 study, habitual dietary intake was modeled based on repeated 24-h diet recalls and a food frequency questionnaire. DNA methylation was measured using the Infinium MethylationEPIC BeadChip providing data on >850,000 sites in this epigenome-wide association study (EWAS). Three metabotype clusters were identified using four standard clinical parameters and BMI. Regression models were used to associate diet and DNA methylation, and to test for effect modification. Few significant signals were identified in the basic analysis while many significant signals were observed in models including food group-metabotype interaction terms. Most findings refer to interactions of food intake with metabotype 3, which is the metabotype with the most unfavorable metabolic profile. This research highlights the importance of the metabolic characteristics of subjects when identifying associations between diet and white blood cell DNA methylation in EWAS.

Usual dietary intake and change in DNA methylation over years: EWAS in KORA FF4 and KORA fit

“…To explore the stability of associations of usual dietary intake of food groups and DNA methylation, we analyzed those food group-CpG associations in the KORA Fit study that were reported as significant in an earlier analysis of our team in KORA FF4 (6). Overall, few results could be reproduced in KORA Fit (Table 3), i.e., reached statistical significance; however, with a much smaller sample size as available in KORA FF4.…”

“…The first studies on diet and DNA methylation were conducted in cancer patients because of the known association between cancer and DNA methylation and the idea to elucidate the potentially harmful or protective effects of diet on cancer (5). Then, research started to look directly at dietary factors that influence DNA methylation and until today focused heavily on micronutrients such as folic acid or B vitamins (6). Mandaviya et al (7) showed associations between dietary folate intake and CpG methylation in an epigenome-wide association study (EWAS), but other groups were unable to confirm these associations (8,9).…”

“…To date, no analyses have examined the longitudinal association of food consumption and temporal change of DNA methylation in mononuclear blood cells. Based on our experience in crosssectional analyses (6,9), we aimed to explore the interaction of diet and time on DNA methylation at the food group level by conducting EWAS on the Infinium MethylationEPIC BeadChip array with 850k CpG sites. Specifically, we assessed the association between food groups and changes in DNA methylation over time.…”

Metabotyping: a tool for identifying subgroups for tailored nutrition advice

“…Although the fibre intervention did not significantly change metabolic parameters across metabotypes, the group with an unfavourable profile had the greatest reductions in insulin, cholesterol parameters (total cholesterol, LDL-C and non-HDL-C) and blood pressure. These metabotypes were also applied to investigate their effect on associations between diet and DNA methylation (28) . While only a few significant associations were observed in the total cohort, many were observed when the analyses were stratified by metabotypes; most of them between methylation sites and the intake of cruciferous, cheese, whole grain products, margarine, eggs and total meat.…”