Our aim is to identify epigenomic marks that are susceptible to the (prenatal) environment and to establish their contribution to human disease. To this end, we apply medium- and high-throughput technologies (mass spectromery and next gen sequencing) and state-of-the-art data-analysis approaches to characterize epigenomic patterns in human cohorts with specific early exposures (e.g. the Dutch Famine), metabolic diseases (e.g. cardiovascular disease) and ageing.
We recently reported differences in DNA methylation of various genes involved in growth and metabolism among individuals who were prenatally exposed to the Dutch Hunger Winter, a severe famine at the end of WW2. These data for the first time indicated that a transient prenatal environment can lead to lifelong epigenetic changes in humans. In addition, they point at a plausible mechanism underlying the link between a compromised prenatal development and disease risk in adulthood.
To systematically characterize epigenomic changes associated with prenatal famine and other environmental exposures, we are performing genome-scale studies. Moreover, we are developing and applying optimal study designs for epigenome-wide association studies (EWAS), bioinformatic approaches for the integration of genetic, epigenomic and transciptomic data and in vitro systems for the functional characterization identified epigenetic marks.
Studies integrating epigenomic, genetic and transcriptomic data may eventually reveal genomic risk factors that are more powerful in predicting health and disease than those solely based on DNA sequence variation.