B1191 - Epigenetic marks at birth maternal pre-pregnancy obesity and weight gain during pregnancy - 21/07/2011

B number: 
B1191
Principal applicant name: 
Dr Caroline Relton (University of Bristol, UK)
Co-applicants: 
Prof Debbie A Lawlor (Not used 0, Not used 0), Eva Morales (Not used 0, Not used 0)
Title of project: 
Epigenetic marks at birth, maternal pre-pregnancy obesity and weight gain during pregnancy
Proposal summary: 

We will investigate if maternal overweight/obesity, variation in GWG, and/or gestational diabetes/glycosuria are related to offspring outcomes and if so, whether this correlates with epigenetic changes. One important concern when studying this is the significance residual confounding specially with socio-economic factors. A Mendelian randomization approach can further address the issue of confounding by using genetic variants, reliably associated with adiposity or glucose metabolism, as instrumental variables for its their causal intrauterine effect. For this purpose, we propose to use single nucleotide polymorphisms that have shown strong associations in previous GWAS with adiposity, or fasting glucose. To have the greatest statistical power we will combine the SNPs into at-risk allele scores. As potential offspring outcomes that can be affected by maternal overweight/obesity, GWG and/or gestational diabetes we will select those phenotypes that have been reported to be associated with adiposity during pregnancy including birth outcomes, child adiposity and vascular traits, and respiratory and neurodevelopment phenotypes. We will take into account the effect of potential covariantes. In addition, paternal body mass index will be used as a control. Our main objective will be to investigate the association between maternal overweight/obesity, variation in GWG and/or gestational diabetes/glycosuria with offspring DNA methylation patterns. If evidence of DNA methylation changes in offspring exposed to developmental over-nutrition is found, a secondary objective will be to assess the association between DNA methylation changes with the selected offspring's outcomes. These analyses could reveal potential biological pathways linking the intrauterine environment of over-nutrition with the development of adversephenotypes in offspring later in life.

Date proposal received: 
Thursday, 23 June, 2011
Date proposal approved: 
Thursday, 21 July, 2011
Keywords: 
Epigenetics , Pregnancy, Genetics
Primary keyword: