A precision nutri-epigenetic approach to tackle the mother-to-child transmission of impaired glucose metabolism
|Partner Organization||Partner Country|
|Forschergruppe Diabetes e.V. am Helmholtz Zentrum München||Germany|
|University of Granada||Spain|
|Universite de Lille||France|
|Erasmus Medical Center||The Netherlands|
|University of Melbourne||Australia|
1. Overall project description
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 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
a. DNA methylation MGR risk scores as nutri-epigenetic based diagnostic tools for preventive/intervention or treatment strategy,
b. dietary recommendations for healthcare, nutritionists, policymakers,
c. an EU-Nutri-Epigenetic-Data platform for researchers/academics, public health policy planners, and
d. 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.
We have completed work on prenatal smoke exposure within PREcisE and EGEA (Wiklund et al, 2019) examining the dose-response relationship between maternal smoking and blood DNA methylation in the offspring. The findings confirm and extend the results of previous studies that maternal smoking during pregnancy has persistent effects on the offspring epigenome and is associated with alterations in offspring blood DNA methylation not only in newborns, children, and adolescents, but also in adults, several decades following the exposure. Also, we show that maternal smoking related markers associate with adult disease outcomes and metabolic measures.
As the global prevalence of maternal smoking during pregnancy varies widely from country to country, from a few percent up to nearly 40%, cigarette smoking continues to be one of the most important modifiable risk factors for the health of mothers and their children. This suggests that there may be potential to intervene in prenatal life to modulate or reverse this adverse epigenetic programming. Public policy actions and guidelines may be improved to better guide strategies for prevention.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Doi|
|Heil SG, Herzog EM, Griffioen PH, van Zelst B, Willemsen SP, de Rijke YB, Steegers-Theunissen RPM, Steegers EAP. [ERASMUS]||Lower S-adenosylmethionine levels and DNA hypomethylation of placental growth factor (PlGF) in placental tissue of early-onset preeclampsia-complicated pregnancies.||10.1371/journal.pone.0226969|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|Master students and teachers||Marjo-Riitta Jarvelin (IC): Northern Finland Birth Cohort Studies – data and some results including early life epigenetics. MSc Health Data Analytics and Machine Learning, London, UK, Jan 2019.||Lecture|
|MSc students, clinicians, nutritionists||Marjo-Riitta Jarvelin (IC): Introduction – Genes and Environment short course, Understanding genetic influence on growth and development, London, UK, Feb 2019.||Lecture|
|Scientists||Janine Felix (ERASMUS); Early-life programming of life course health. Helmholtz Zentrum für Umweltforschung UFZ, Leipzig, Germany, Feb 2019.||Lecture|
|Scientists||Janine Felix (ERASMUS); Maternale Faktoren und (Epi-)genetik - 45 Jahrestagung der Gesellschaft für Neonatologie und Pädiatrische intensivmedizin, Leipzig, Germany, May 2019.||Lecture|
|Scientists||Steegers-Theunissen RPM (ERASMUS). Periconception one carbon metabolism and embryonic and placental health, 12th International conference on One Carbon Metabolism, B Vitamins and Homocysteine, Reus, Jun 2019 (invited speaker).||Lecture|
|Public Outreach||Janine Felix (ERASMUS); Biosamples panel session during the “Born in Bradford” Science Festival 2019, Bradford, UK, Oct 2019 (participated in the panel).||Panel session|
|PhD students||Marjo-Riitta Jarvelin (IC): Research Design for Social Sciences and Medicine. Three-hour interactive session including aspects of genetic/epigenetic studies. Imperial College Graduate School, London, UK, Feb 2019.||Lecture|
|Master students and teachers||Marjo-Riitta Jarvelin (IC): Lifecourse models – data – on metabolic traits addressing early life epigenetics. MSc Health Data Analytics and Machine Learning, London, UK, Nov 2019.||Lecture|
|Master students||Janine Felix (ERASMUS). DNA methylation. Course “SNPs and human diseases”, Erasmus MC, Rotterdam, the Netherlands, Nov 2019.||Lecture|
|Scientists||Sandra Hummel (FDeV); Intergenerational metabolomics in women with GDM and their offspring – DZD Workshop, Munich, Germany. Oct 2019.||Short talk|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|