PREcisE’s overarching goal is to use longitudinal data from the pre-conceptional period up until adulthood to explore the life-course and molecular pathways pertaining the mother to offspring transmissibility of impaired glycaemic health. The project harnesses very large data from cohorts/biobanks and studies from Spain, Germany, Finland, France and the Netherlands. It also joins hands with related projects (e.g. ALPHABET & NutriPROGRAM) and other consortia (e.g. PACE: Pregnancy And Childhood Epigenetics, EGG: Early Growth Genetics, MethQTL: Global Methylation Collaboration) to study and establish the mother-to-offspring transmission of glycaemic health through robust epigenetic factors. In particular, PREcisE’s main objectives are:
1. To identify robust epigenetic marks in the offspring demarking an exposure to adverse maternal glucose metabolism during pregnancy. Epigenome-wide association studies to identify Maternal Glucose Responsive (MGR) loci in the offspring will be performed.
2. To characterise the underpinning molecular pathways and the tissue specificity through gene expression analysis in human liver, skeletal muscles and adipose tissue.
3. To explore the role of pre- and postnatal nutrition in modifying impaired maternal glucose programming. Data on maternal and postnatal dietary behaviour across the different observational studies and RCTs in the Consortium will be harmonised to systematically analyse how dietary behaviour may be either causal or effect modifier of the programming induced by exposure to maternal glucose adversity.
4. To demonstrate the life-course pathways pertaining the mother-to-offspring transmission of impaired glycaemic health and identify the opportunity to impact. State of the art statistical methodology (Bayesian Structural Equation Models) will be employed to examine the interplays between maternal glucose, epigenetics and offspring impaired glycaemic health.
5. To exemplify the lasting impact of adopting healthy dietary behaviours from pregnancy onwards on lifelong health. The project’s main results will be exploited to support the development of
- DNA methylation MGR risk scores as nutri-epigenetic based diagnostic tools for preventive/intervention or treatment strategy,
- dietary recommendations for healthcare, nutritionists, policymakers,
- an EU-Nutri-Epigenetic-Data platform for researchers/academics, public health policy planners, and
- a life-course analysis framework for the mother to offspring transmissibility of impaired glycaemic health for scientists and public health specialists.

Evidence is emerging to support that a range of pre- and postnatal life-style exposures (e.g. gestational diabetes mellitus (GDM) of the mother, maternal smoking, nutrition) may have impact on the epigenome and can induce epigenetic marks (DNA methylation marks) that predict risk of metabolic disease later in life.
Here we will summarise also core from previous year and then update by reporting year’s progress. During the first year of the project we completed a work on prenatal smoke exposure within PREcisE (Wiklund et al, 2019) showing the dose-response relationship between maternal smoking and blood DNA methylation in the offspring, permanency of several of these methylation markers and associations with some causal evidence with adult disorders. These observations have clear public health importance. Public policy actions and guidelines may be improved to better guide strategies for prevention.
Within WP1 we have undertaken and completed multiple EWAs meta-analyses to investigate the associations of maternal glycemic health metabolism during pregnancy with offspring DNA methylation (DNAm), discovering one of the best studied epigenetic marks to date. In particular, we have investigated DNAm profiles in new-born blood and blood collected in later childhood in relation to maternal fasting glucose levels (plasma or whole blood values), maternal glucose response to oral glucose tolerance test (OGTT) and maternal fasted serum insulin levels during pregnancy. The projects are co-led by PREcisE researchers and our collaborators in the PACE consortium.
The analyses show the association of maternal glucose OGTT (area under the curve) with child DNAm and identify two adjacent CpGs in the well-known TXNIP gene. TXNIP methylation has been previously found to be associated with metabolic phenotypes and future T2D risk. Both CpGs in TXNIP in our analyses have not yet been described in literature and follow-up in PREcisE partner cohorts show that DNAm at these CpGs is also associated with maternal T1D exposure in children and multiple glycaemic and anthropometric traits in adults.
These two probes will be further tested in WP3 within also a life-course context for associations with adult metabolic phenotypes taking into consideration potentially modifiable co-variates (e.g. genetic, behavioural and life-style factors of the mother and the offspring. These results will help to understand ways of avoiding related diseases which, from a public health perspective, may be used to improve guidelines and strategies for prevention.
Within WP2 we have completed the harmonisation of dietary indices between cohorts, to be included as pre- and postnatal exposure variables in ongoing meta-analysis on DNA methylation during childhood and adolescence. The harmonised dietary indices include the glycemic index and glycemic load as well as the dietary inflammatory index which has been revised to improve its application in multi-cohort collaborations. A manuscript on the revised calculation of the dietary inflammatory index is currently under preparation.