Research Objectives:

The purpose of this project is to determine the effect of deviations from expected birth weight on later life outcomes within the ALSPAC cohort. The study will have the following two specific aims:

1. To develop and validate a method of determining expected birth weight9, 10 through the use of a prediction equation to be developed based on the relationship between gestational age, parity, gender, and other maternal characteristics (age, height, weight, smoking status, mother's own birth weight) and birth weight of offspring in the ALSPAC cohort.

2. To relate deviations from expected birth weight to a set of later life outcomes in the ALSPAC cohort including markers of cognitive development and function and cardiovascular disease outcomes.

AIMS

The purpose of this proposal is merely to obtain approval to ask the accompanying questions. We will submit further proposals for any analysis we wish to carry out.

Aims

1)We will test the hypotheses that risk alleles in the general population impact on pre-pubertal neurodevelopmental domains involving 1) emotion/mood regulation 2) cognition/learning 3) social cognition/communication and 4) behaviour regulation.

2) Test the hypothesis that mental disorder RP scores that we find to contribute to domains of neurodevelopment at age 7/8 years have longitudinal effects.

3) Test that bullying/victimisation at 7/8 years further predicts longitudinal change in RP score-associated neurodevelopmental domains.

Aim

The overall aim of the study is to investigate how sibling bullying relates to peer bullying in order to find the embryonic origins of bullying.It is planned to go about this by longitudinally studying sibling bullying. The overall study is broken down into two parts: The first part will examine the precursors of sibling bullying, the second part will examine the outcomes of sibling bullying, inclusive of examining how sibling bullying relates to peer bullying.This break down is done in order to answer the following questions: (1) what factors influence sibling bullying (as a bully, victim, and bully-victim)? (2) What are the specific outcomes of sibling bullying (as a bully, victims and bully-victim)? (3) Are there cross-over effects from a sibling bullying dynamic to a peer bullying dynamic? (4) Should there be cross-over effects, how strong are they? Do bullies, victims and bully-victims at home, remain in their respective roles in a peer bullying dynamic?

AIMS:

1. To assess the prevelance of rare deleterious mutations (RDMs) in control cohorts (ALSPAC and TWINSUK) and in neuropsychiatric disease cohorts sequenced as part of the UK10K project.

2. To assess the phenotypic correlates of carrying such mutations.

AIMS:

The aims of this research are therefore to examine the impact of domestic violence as measured in the ALSPAC cohort on the behavioural and emotional development of children up to age 8 years, and examine factors that may increase the likelihood of resilience. In particular, both physical and non-physical forms of domestic violence, and the parental role in the impact of violence on child outcomes will be explicitly examined. The research questions to be addressed are:

1. There will be variation in the behavioural and emotional development of children exposed to domestic violence;

2. The variation in behavioural and emotional development of children exposed to domestic violence will vary depending on which parent used violence and which parent was victimised;

3. The variation in behavioural and emotional development of children exposed to domestic violence will vary depending on the type of domestic violence to which they were exposed (physical, emotional, combined);

4. Children who are identified as resilient in the context of physical domestic violence will be identified as resilient in the context of non-physical domestic violence;

5. The relationship between exposure to domestic violence and child development will be mediated or moderated by: maternal depression; parenting quality; child's cognitive ability and child's temperament.

Aim:

To develop statistical methods to model the variability of clinically-relevant measures within an individual, and relate this variability to both exposures and outcomes. We will develop methods for nominal and continuous exposures and outcomes, and both intensively and sparsely collected data. We will then apply these methods to simulated data,and to the ALSPAC example.

Aim 1:Telomere dynamics from birth to adulthood. We propose to characterize telomere length and its rate of erosion across various developmental periods between birth and 25 years of age.

Aim 2: Pre-natal health of mothers and early-life telomere dynamics. We propose to assess the longitudinal association between maternal body mass index, HDL/LDL ratio, cholesterol and triglyceride levels during the first trimester, and gestational diabetes as reflected by blood glucose levels in the mothers, and the rate of telomere erosion from birth to 25 (?) years of age in their children.

Aim 3: Early-life telomere dynamics and cardiovascular / metabolic outcomes in early adulthood. We propose to assess the longitudinal association between the rate of telomere erosion in children from birth to 15 years of age, and cardiovascular / metabolic health outcomes 5 - 10 years later including arterial stiffness, blood pressure, intima-media thickness, HDL/LDL ratio, triglyceride levels, flow-mediated dilation, adiposity, and fasting blood glucose.

We plan to collect dietary data as part of the clinic being planned in the ALSPAC participants.They will be asked to complete three 24-hour dietary recalls, using a newly developed online system (exact tool to be determined - we are currently negotiating with two research groups over their tools: Jane Cade's MyFood24 (Leeds University) and Emma Foster's INTAKE24 (University of Newcastle)) at around the age of 24. YPs will be requested to complete a recall prior to coming to a clinic planned to start in June 2015. There will then be opportunity for the YP during the clinic visit to ask any questions about their dietary recall. The tool we use will automatically provide us with all the data necessary (food groups and nutrient intakes as derived using standard food tables). The tool will be both smart phone and tablet compatible. This means at least one recall could be collected during the clinic visit if time is available between sessions (we anticipate it will take 10-15 minutes to complete one recall) if we were to purchase a number of tablets. Reminders will then be sent out via email/text after the clinic visit to complete futher 24-hour recalls.

We also propose the collection of new questionnaire data in the YPs, to include questions such as current living arrangements (who, what, where), what the YP is currently doing (work, study etc), who normally prepares food etc and other eating behaviours. Such questions will be included in either the 2014 or 2015 Q as appropriate (but ideally 2014 from a temporal point of view, though we acknowledge funding may not be in place in time).

In addition to examining food groups and nutrient intakes, we will use three methods: cluster analysis, principal components analysis and reduced rank regression to obtain dietary patterns: All these methods reduce the complex nature of many inter-correlated dietary variables into a smaller number of variables which best describe the overall patterns of diet in the population but result in different outcome variables providing slightly different ways of assessing overall diet. These methods have been used extensively by the applicants to determine dietary patterns throughout childhood and into adolescence and will be used to see whether dietary patterns track into adulthood.

The ALSPAC resource provides the perfect opportunity to develop causal models that will explore which of the following are most important in determining 'healthy' dietary intake in early adulthood:

* Individual factors such as previous diet (including breastfeeding and weaning and dietary intake throughout childhood and in early adolescence), eating behaviours (such as skipping breakfast) physical activity, body composition, life events and other health behaviours;

* Familial factors such as parental diet, eating attitudes and behaviours, lifestyle and health factors

* Social and environmental factors such as housing, education of both the individual and their parents.