Epigenetics

The Molecular Epidemiology lab aims to discover molecular determinants of common human diseases including cardiovascular disease and human longevity. Our main focus has been genetic research. Recently, the hypothesis that epigenetic mechanisms also contribute significantly to the risk of cardiovascular disease and the chance of becoming long-lived has attracted much attention. This hypothesis, however, awaits systematic testing. This project is geared towards finding the first evidence for a role of epigenetic variation in cardiovascular disease and longevity. If true, this opens the possibility for new therapeutic strategies: after all epigenetic defects have a much better prospect for treatment than DNA sequence variation.

Research questions

Our central hypothesis is that epigenetic programming in utero leads to inter-individual variation in gene expression and thereby in he risk of disease later in life. This is based on studies in mice showing that feeding mothers a methyl-deficient diet during pregnancy causes a specific gene to become unmethylated in offspring, which causes a yellow coat colour. Moreover, we showed in our own human studies that low birthweight, a marker for prenatal nutrition, (Twin studies) and prenatal exposure to famine increases cardiovascular risk later in life (Dutch Hunger Winter Study). In the current project, DNA methylation patterns will be assessed in twin pairs who have a different birthweight and in individuals who were prenatally exposed to famine during the Hunger Winter at the end of WWII as compared with their non-exposed siblings. Methylation patterns will be measured in sets of candidate genes (e.g. IGF2, TNDM, TNF, APOC1) using a new mass spectrometry-based method and, genome-wide, in 8000 CpG islands using micro-arrays. Methylation status will be linked to prenatal nutrition as well as genetic variation to determine the cause of epigenetic variation, and to cardiovascular risk later in life to determine its consequence. Next, DNA methylation will be assessed in longevity families (Leiden Longevity Study) and clinical studies on myocardial infarction (GENDER, PROSPER). 

Techniques 

Mass-spectrometry to quantify DNA methylation in a high-throughput fashion; CpG island micro arrays to establish DNA methylation differences for 8000 CpG islands; Robotics; Contemporary statistical analysis; Application genomics databases.

For further information have a look on the Molecular Epidemiology website