Using genetics to understand how the maternal intrauterine environment influences fetal growth. (360G-Wellcome-104150_Z_14_Z)

The primary aim of this project is to use analyses of genetic data in the largest and best-characterised studies of mothers and offspring to understand which factors in the maternal intrauterine environment are causally associated with birth weight. I will construct and validate genetic risk scores for maternal traits (including fasting glucose, BMI, vitamin D levels) and test these for association with offspring birth weight in a meta-analysis of 245,000 individuals from the UK Biobank and E arly Growth Genetics (EGG) Consortium (including N=37,000 accurately phenotyped individuals and N=25,220 maternal-fetal pairs to control for confounding by fetal genotype). Strong evidence of association between a genetic risk score for a maternal trait and birth weight will indicate a causal association. Further analyses of associations between genetic risk scores and cord-blood insulin levels, neonatal adiposity and postnatal growth will enable us to begin to characterise the mechanisms linkin g causal maternal factors to fetal growth. The identification of causal associations will provide extremely important information linking modifiable maternal factors with offspring birth weight and thereby informing decisions on pregnancy management for healthy fetal growth.