TA 4: Genetic and epigenetics factors as a biological link between food intake and cognition/neurodegeneration

Which genetic and epigenetischen factors play a role with neuro-degenerative disease?

Understanding of the molecular genetic factors that underlie the relationship between nutrition and the development of illness is limited. The influence of nutrition on cognitive ability and neurodegenerative disease is mediated by various, as yet largely unknown, biological pathways. The possibilities offered by modern genetics and epigenetics render stepwise characterization of these pathways feasible. Individual human genetic constitution will also have an influence on these processes, and modulate the effects of nutrition via gene-environment interactions. For the purposes of our analyses, we will use data from various cohorts (TTTS, DONALD study, Rhineland study, AgeCoDe).

Twin to twin transfusion syndrome (TTTS) study

In the 1st period a unique German registry of 40 twin pairs with twin-to-twin transfusion syndrome (TTTS) were investigated. TTTS occurs in monozygotic twin pregnancies with a single, common placenta. In TTTS, a temporary discordance in prenatal nutrient exposure occurs, resulting in unequal nutrition between the acceptor and donor twin. DNA from all 80 individuals, and performed genome-wide genotyping and DNA methylation analysis were obtained. Further, cognitive and behavioral characteristics were assessed using different tools (e.g, KIDSCREEN-52, WAIS-IV). In this period an integrative analysis in order to identify genetic and epigenetic factors that confer the effect of prenatal nutritional status on cognitive performance and behavior should be performed.

DONALD study / DELCODE Study

In the first period genetic Data were collected and a DNA- and RNA-bank was established. These data will be used to explore the interaction between genetic and epigenetic factors and nutrition during childhood and adolescence.

The DELCODE study is used to perform genome-wide methylation profiling in a subset of 200 individuals from the DELCODE study. All DELCODE participants undergo detailed phenotyping, including MRI, AD biomarkers, and data on cognitive function.

Investigation of genetic and epigenetic effects

The interaction between nutrition and cognitive performance in relation to individual genetic constitution will be analysed. Here, individual single nucleotide polymorphisms (SNPs) only will have small effect sizes, and large samples sizes are required to detect these small effects. Therefore the data of a larger sample/dataset (UK Biobank, see (i)) will be included, and will apply pathway- and genetic score based approaches (see (ii-iii) in the in-depth characterized DietBB cohorts.

Research questions and objectives

O4.1 To maintain and expand DietBB DNA biobanks and to generate new genetic and epigenetic data.

O4.2 To study the interaction between nutrition, lifestyle, and cognitive performance, taking into account genetic predisposition for obesity-related traits, microbiome composition, behavioral traits, and food preferences.

O4.3 To determine whether: (i) dietary induced epigenetic changes in early childhood persist into later life; (ii) dietary pattern and energy restriction interventions lead to epigenetic changes in methylation profiles; and (iii) the respective epigenetic signatures are associated with cognitive performance across the life span.