The EPIPREG project
Genetics and epigenetics in a population-based, prospective cohort of pregnant women
Primary Investigator: Christine Sommer
Gestational diabetes (GDM) is hyperglycaemia first recognized in pregnancy. Although normoglycaemia usually ensues after birth, the mother has extensive risk of future type 2 diabetes (T2D). GDM is a highly valuable model to study T2D, as they share many pathophysiologic and genetic features. Pregnant women also provide a diabetes model with a lower degree of immediate confounding by smoking and alcohol consumption, known to affect DNA methylation and several other outcomes.
The STORK Groruddalen study is a population-based, prospective cohort study of 823 pregnant women living in the Groruddalen area of Oslo, 2008-2010. Fifty-nine percent of the sample were of non-European origin, mainly from South Asia and the Middle East.
We have genotyped all women with adequate DNA (n=644, n=613 remaining after quality control) using the 450k CoreExome beadchip from Illumina. In the EPIPREG project, we have quantified epigenome-wide DNA methylation in white blood cells of all Europeans (n=312) and South Asians (n=168) from the STORK Groruddalen cohort, using the epigenome-wide Infinium MethylationEPIC beadchip from Illumina (at about 850 000 sites).
In addition, we have an extensive list of phenotypes, both in the mother and her offspring as well as some paternal phenotypes. Our unique population-based sample for epigenome-wide association studies enables the study of several exposures and outcomes.
We hope to identify cohorts with similar data to perform meta-analyses of these to increase the statistical power. We will verify our results in vitro in human myotubes and adipocytes, and explore whether silencing of the promoter region relative to the CpG hits lead to change in glucose and lipid metabolism, insulin signalling.
This project will increase our understanding about the underlying mechanisms of how lifestyle, genetics and epigenetics are associated with development of obesity and GDM, to ultimately improve diabetes prevention and pharmacological treatment strategies, and delay onset.
Do you have epigenome-wide DNA methylation data to allow for meta-analysis of results? Or a great research idea and the ability to conduct it but lack the data? Please contact Christine Sommer!