We are investigating the role of epigenetic processes that contribute to developmental influences on later health. In 2006 we established the EpiGen Research Consortium comprising: (a) MRC Lifecourse Epidemiology Unit and University of Southampton Institute of Developmental Sciences; (b) Liggins Institute, University of Auckland; (c) AgResearch Ltd, New Zealand; (d) Singapore Institute of Clinical Sciences (Growth, Development and Metabolism programme), an operating unit of A*STAR; (e) National University of Singapore (Translational and Clinical Research flagship programme, “Developmental pathways to metabolic disease”).
We have shown that epigenetic processes predict childhood adiposity: greater methylation of two CpGs within the RXRA promoter measured in umbilical cord was robustly associated with greater adiposity in later childhood. The associations reflected clinically important shifts in body composition. Our analyses showed that gender and neonatal epigenetic marks explained over 25% of the variance in childhood adiposity. The findings were replicated in a second independent cohort (see figure).
To identify new biomarkers and novel pathways that mediate developmental influences on NCD risk, (with our co-investigators at the Institute of Developmental Sciences, University of Southampton) we are exploiting a discovery pathway that combines candidate and genome-wide screens for methylation differences at birth that are associated with childhood outcomes (figure 2).
Elucidation of epigenetic processes may permit perinatal identification of individuals at risk of later NCDs and enable early intervention strategies to reduce such risk.