Using genetics to understand causal mechanisms underlying adverse outcomes of obese pregnancies

More than 1 in 5 UK pregnant women are clinically obese, a condition associated with heterogeneous health outcomes for mother and baby. Only limited understanding of the associations (e.g. gestational diabetes and high birth weight, hypertension and preterm birth/low birth weight) has been possible in traditional observational studies due to complex interrelated exposures and outcomes. My research will use human genetics to dissect causal pathways and understand how a higher maternal BMI can lead to such diverse outcomes. I hypothesise that maternal effects on fetal growth and gestational duration are moderated by fetal genetics. My first aim is to understand how a fetus regulates its own growth and gestational duration in different maternal environments. We will apply results of new genome-wide association studies of placental weight and umbilical cord insulin to give mechanistic insights. My second aim is to understand how raised maternal BMI impacts gestational duration and growth, and my third aim is to examine whether fetal genetics can influence the maternal environment. By identifying causal mechanisms, this fellowship will be an advance towards better targeting of antenatal healthcare and advice to pregnant women, according to their level of risk to reduce the incidence of adverse pregnancy outcomes.