Aims: There are many relationships between features of lifestyle and other exposures to the parents that have been shown to be related to the growth, behaviour and development of the child, but there is rarely a convincing mechanism to explain how they occur. This study aims to determine, for each of the known relationships, whether DNA plays a part in the mechanism.

The hypothesis is that DNA methylation is a mechanism to 'explain' a number of relationships between the environment and measures of growth, cognitive development and behaviour. The presumed mechanism is shown diagrammatically as follows:

Exposure to parents ? Methylation of mother's and/or child's blood ? child outcome

Exposure variables: The proposed study will concentrate on exposures related to toxins (particularly cigarette smoking), ionising radiation (especially X-rays and radon levels in the residential areas in which the parents were born and currently live which can be linked to 3-digit postcode using published data), nutrition (especially related to fish intake and to dietary patterns in pregnancy), and stress (particularly acute stressors during the parents' life-course, chronic stressors using social circumstances, and measures of their anxiety levels). Exposures to the parents and grandparents will be included.

Outcome measurements will concentrate on growth, behaviour, intellectual development and educational attainments (including SATS results as well as the ALSPAC assessments of maths, reading, spelling, scientific understanding and phoneme awareness).

Confounders will be chosen based on the original reports of an association between an exposure and an outcome. It is important to recognise that we are mainly testing the possibility of DNA methylation explaining relationships that have already been reported.

A variety of statistical analyses will be undertaken: (i) relationship between prior exposures to the mother and her parents and methylation of the mother's blood; (ii) relationship between the mother's methylation pattern and that in the cord blood; (iii) relationshipbetween exposures to both parents and grandparents andthe methylation levels of the cord blood; (iv) determination of ways in which these methylation patterns may explain how relevant exposures have influenced outcomes.