The Developmental Origins of Health and Disease (DOHaD) theory is now well established, linking intrauterine and early-life growth with adult cardiovascular and other disease, with increasing evidence for the role of gene-environment interactions underlying this association. Evidence suggests that much of the variation in fetal growth is mediated by changes within components of the hypothalamic-pituitary-adrenal (HPA) axis. This system is also key in regulating blood pressure and therefore is a clear target for research into the links between fetal growth and adult hypertension.

We hypothesise that genetic variations within the HPA axis will show significant associations with fetal growth trajectories and longitudinal blood pressure trajectories in childhood, adolescence, and adulthood, and may therefore represent one of the genetic mechanisms underlying the developmental origins of hypertension.This study aims to test this hypothesis by identifying associations between single nucleotide polymorphisms in the genes within the HPA axis and:(1) antenatal growth trajectories; and,

(2) childhood and adolescent blood pressure trajectories.

We will identify among these associations genes which are known to relate to adult hypertension.

This project will utilise the resources of two international cohorts:

(1) The Western Australian Pregnancy (Raine) Cohort will be studied for the associations between the SNPs and fetal growth and childhood and adolescent blood pressure trajectories to age 17.

(2) The ALSPAC cohort will be studied for the associations with childhood and adolescent blood pressure trajectories.

Preliminary analysis of the data from the Raine cohort suggests significant genetic associations with all of the proposed outcomes and we aim to replicate these associations within the ALSPAC cohort