Summary of aims and objectives: This study will capitalise on environmental, biological and

behavioural data that, together with sequential DNA collections over four time points, from infant

and child saliva, are already available from the Wirral Child Health and Development Study

(WCHADS). This is an MRC funded cohort recruited in pregnancy and followed, so far, to age 5

years, established to identify prenatal, infancy and early childhood risks for child psychopathology.

There is a strong focus on early processes underpinning risks for the conduct disorders, but with

emerging findings also in internalising symptoms. The study has limited funding for genotyping but

none for epigenetics. It is distinctive among cohort studies in using a two stage design that enables

detailed observational and experimental data obtained during pregnancy, infancy and childhood to

be conducted on an epidemiological sample. We are not aware of any other studies that combine

such intensive measurement with sequential DNA collection early in life. We will carry out

comprehensive analyses of DNA methylation allowing us to develop a detailed picture of the

epigenome and gene regulation over early development and in relation to continuities and

discontinuities in early experiences, and stable and changing behavioural phenotypes. The case for

the application is made on the basis of the distinctiveness of the data available from this sample,

and also the degree of overlap and complementarity with collaborating studies, which will allow for

data sharing and replication of novel findings. So far collaborations on methylation analyses have

been established with Barker & Mills (NIH funded study) who have a study of methylation pathways

to conduct disorder using a subsample of ALSPAC participants; Generation R Holland, Teiemier;

McGill University, Canada, Meaney, O'Donnell. We also anticipate collaborative data sharing with a

much wider range of groups, especially those that have identified methylation over regions of

interest later in life, and wish to examine the contributions of early experiences in those regions.

Specific aims include a) to provide evidence on methylation patterns mediating links between

prenatal and early postnatal environmental exposures and later biological and behavioural

outcomes, b) examine the role of differential methylation in explaining gene by environment

interactions in early development, c) use environmental predictors to identify novel environment

sensitive regions of the genome for further study in relation to behavioural phenotypes, d) make use

of our repeated DNA and observational measures to extend findings in other studies, e.g. examine

earlier methylation patterns through infancy in pathways to conduct disorders identified in a

subgroup of the ALSPAC cohort (NIH; Barker & Mills) on the basis of methylation estimated at birth

and later childhood at ages 7 and 9 years.