The optic nerve is of key importance for the development of glaucoma and its impairment is the second largest cause of blindness worldwide. Although adult studies have described normal variation in the optic nerves of healthy individuals, there are no population-based data that systematically describe variability of the optic nerve in children. It is not known whether the optic nerve remains of a constant appearance after birth until disease may develop in middle-age, or whether important changes can occur in early life. Furthermore, children with atypical optic nerves are frequently investigated to exclude serious illness, because of the difficulty in characterizing normal variation in optic nerve appearance.

We propose to add much-needed data to the literature by taking the opportunity to grade a recently acquired library of retinal pictures from a population birth-cohort of healthy 12-year old children. The appearances of the optic nerves will be described, and any associations with individual characteristics such as birthweight and refraction will be noted. The pictures are already available, only the staff time to grade them is required, together with time to prepare papers for dissemination of the results. This unique opportunity will provide valuable data that will benefit opthalmologists, researchers and patients.

(No outline received).

(No outline received).

The study team have been granted access to video data from the ALSPAC Children in Focus study. This sub-cohort consists of over 1000 children, most of whom were videoed with one or both parents using the Thorpe Interactive Measure, in which parents are asked to look at a book with their infants.

Almost all of these children had a psychiatric assessment (the DAWBA) at age 91 months. The cases are:

* 18 with ADHD,

* 32 with oppositional-defiant or conduct disorder,

* Six with pervasive development disorder (PDD)

* 26 with one or more anxiety disorders

* Five with a depressive disorder

There will be two controls per case, picked to be frequency matched on age (corrected for gestation) and gender.

This adds up to 261 videos to be analysed. As far as we know this is a unique dataset potentially allowing assessment of early behavioural predictors of child neuropsychiatric and psychiatric conditions. Our team have already developed techniques for detailed behavioural analysis of video material and have the necessary software and hardware.

We propose in this competing continuation to extend our current project examining the association between physical activity and obesity within ALSPAC by repeating the objective physical activity measures at age 15. These extended measurements will allow us to further explore the associations between physical activity, obesity and CVD risk factors prospectively in this large contemporary population-based study of children.The 15-year clinic has started (October 2006) and we are managing to collect collecting data during this interim period using our existing resources from the original grant (staff, equipment, etc). If we are unsuccessful with the renewal application we will cease measurements when the current grant ends (May 2007).

The fetal over-nutrition hypothesis suggests that mothers who are overweight, gain weight rapidly during pregnancy, have high energy diets and those with on averagehigher glucose, insulin and lipid levels (even in the absence of diagnosed gestational diabetes or lipid abnormalities) programme their offspring to become overweight/obese and have vascular and metabolic problems later in life.If this hypothesis is correct then it would have major public health consequences since overweight/obese mothers would programme their offspring to be overweight/obese and have poor vascular and metabolic function; for their female offspring this would mean that they similarly went into their pregnancies overweight and with relatively high glucose and lipid levels, and would thus do the same with their offspring.Consequently, it is feared that if this hypothesis is true then interventions to reduce the obesity epidemic will fail to have any population impact for many generations.Despite this concern there is little high quality research that has attempted to test this hypothesis. Work in animal models demonstrate proof of principle,but may not be generalisable to humans. The small number of studies undertaken in humans have failed to use robust methods for demonstrating a specific intrauterine effect, as opposed to shared familial (environmental or genetic) effects, and have failed to adequately control for potential confounding factors.

Obesity in children is on the increase, and is associated with heart enlargement. This could be due to increases in the load on the heart, although abnormal nervous control of the heart or altered arterial function could also contribute. Low birthweight children, who exhibit accelerated growth through childhood, may be particularly affected. We will use non-invasive techniques to examine heart and arterial structure and function in 2500 fifteen year olds who have been part of a detailed study of growth since birth. This will help us understand why obesity results in heart disease, and why adolescents who have grown rapidly in childhood are at particular risk.

The main scientific and technological objectives of this highly focused RTD project are:

* to carry out well-integrated genome-wide and functional genomics research in order:

o to identify genetic risk markers for CAD

o to link these with transcriptome data and cellular function in atherosclerosis

o to discover new candidates and systems for drug development

o to exploit Intellectual Property Rights (IPR) in partnership with SMEs and the pharmaceutical industry

o to develop integrated novel information systems

* to establish a world-leading European consortium on the basis of genuine and equal partnership between leading clinical centres, academic groups, cell biologists, bioinformaticians and biostatisticians to provide further knowledge into the genetic basis of CAD for the benefit of members of the European Community.

To test already postulated relationships between the environmental exposures and refractive error development in the ALSPAC cohort, using existing data (non-cycloplegic autorefraction

To obtain axial length measurements on the ALSPAC cohort of childrenat the age of 15 and use these data to confirm/modify the results from phase

To carry out cross cohort comparisons with another cohort study that is dedicated to the development of myopia (the Singapore Cohort study Of Risk factors for MyopiA- SCORM) and has comparable, wide-ranging data.