Aims of the study

The primary aim of this project is to identify the methylation pattern across the genome of cord bloods of children taking part in ALSPAC, and identify how they vary with features of the environment. The environments to be considered include not only the exposures during pregnancy, but also the parental exposures during their own childhood and even that of their parents where available.

Having identified these patterns, the project will be available for a variety of programmes to be funded in the future:

(a) To test the ways in which the methylation patterns in cord blood are associated with health and developmental outcomes measured throughout childhood and adolescence;

(b) To determine how environmental influences between birth and 7 years influence changes in methylation from birth

(c) To assess the differential influences of the two methylation records (birth and at 7) on the childhood outcomes.

Methodology

Currently there are only about 3500 {Sue will update} DNA samples obtained from cord blood. However there are still xxxx white cell pellets from which DNA can be extracted. It is proposed that these pellets be extracted as phase 1 of this project. The funding for this will be included in the proposal.

Once the DNA is available, around 500ng per child will be delivered to the laboratory that will carry out the assays, probably using the new Illumina chip. However, that will very much depend on which genes are included on the chip. The other task for the first year of the project will involve identifying the key genetic variants that need to be included. [N.B. Marcus has suggestions as to who will do the chip assays, but is in Japan at the moment. I will get back to you when he is back]

The methylation patterns will be analysed by statistical experts employed by this project, and linked to the various exposure variables that will have been prepared by JG and team as an exposome. The methylation patterns and the exposome variables will be fully documented and deposited wherever the Exec deems appropriate.

It is envisaged that a number of collaborators will be involved in the initial writing up of the results. The exposures and likely collaborators are listed on the next pages.