The Developmental Origins of Health and Disease (DOHaD) hypothesis
predicts that environmental exposures experienced early in life modify risk
associated with later onset disease. DOHaD is supported by a large number of
direct animal studies and a smaller number of compelling observational studies
in humans, but the mechanism(s) underlying the ‘programming’ of DOHaD effects
remain largely unclear. Epigenetic variation has rapidly emerged as a candidate
mediator of such effects. However little direct evidence exists in humans,
primarily due to the inherent problems associated with unraveling the relative
contributions of genetic and environmental influence to phenotypic outcome. Our
team aims to address some of these knowledge gaps through the establishment of
longitudinal human cohorts of varying design, commencing prior to birth, with
detailed environmental, clinical and other data, and extensive biospecimen
collection. Such studies are key to providing direct evidence in support of a
role of epigenetic processes as a driver of DOHaD in humans.