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.

Aims:

To examine whether temporal orderings exists between the three higher order factors of psychopathology; internalizing, externalizing and psychosis.

Aims

Early puberty is associated with poor mental health outcomes in adolescence, from diminished mental wellbeing to psychopathology, especially amongst females. Explanations for this observed association predominantly centre on developmental mismatching of cognitive and emotional capacities and social engagement with older rather than same age peers. Research in this area has, however, largely neglected to examine the extent to which mental health issues precede premature pubertal development.

Life history theory considers early pubertal development to be an adaptive response to early environmental adversity, including factors such as familial discordance, hostile or neglectful parenting and low resource stability including family economic hardship. These social determinants of early puberty are also known to be related to behavioural problems and psychosocial difficulties (e.g., Boe et al., 2012). The inter-related nature of these outcomes and their timing require further exploration. Relevant longitudinal research in this context (Mensah et al., 2013) has recently revealed psychosocial and behavioural adjustment issues among four year-olds that go on to experience premature puberty. Utilisation of ALSPAC data will enable further generalisation of this research. We aim to follow up and extend research in this area by examining the extent to which psychological health, health-related behaviour, neurodevelopmental disorders and cognitive abilities in early childhood vary according to subsequent pubertal timing.

Pubertal timing is strongly controlled by genetic factors (heritability of menarcheal timing is estimated to be as high as 74%; He & Murabito, 2014). Both genome-wide association studies and candidate approaches have identified these factors which are among the most robust findings in the field of complex trait genetics. We would like to include genetic variants in our analysis to control for genetic influences and also test whether genes associated with pubertal timing in boys and girls could be directly implicated in related psychological and behavioural phenotypes. Interestingly one of the genes identified, CYP19A1, has also been implicated in dyslexia, a common neurodevelopmental phenotype. For this reason, we would like to include reading-related measures in our dataset. Also pertinent to this context are findings of sex differences in neurodevelopmental disorders (e.g., Willcutt & Pennington, 2000). We aim to examine potential environmental and genetic factors which may contribute to gender differences in prevalence rates.

This project builds on a collaboration between research groups in the School of Medicine, University of St Andrews, which is focusing on a wider project on the determinants and consequences of early pubertal timing. Professor Candace Currie currently acts as International Coordinator of the 43-country Health Behaviour in School-aged Children (HBSC) study and directs the Child and Adolescent Health Research Unit (CAHRU) in St Andrews. Professor Currie has a strong track record in fields of puberty and adolescent health and has been an active researcher in these areas for over 20 years. Dr Silvia Paracchini is a Royal Society University Research Fellow and an active researcher in the field of neurodevelopmental genetics. She has extensive experience in working with cognitive measures from the ALSPAC dataset. Dr Ross Whitehead is a Research Fellow with the Scottish HBSC team and has backgrounds in cognitive neuroscience and the evolution of human behaviour. As part of our collaborative project, we will extend our analysis to other relevant existing cohorts such as the 'Generation Scotland' study, which allows retrospective investigation into some of the above research questions

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.

Aims:

To analyse the mothers' total blood selenium in regard to the subsequent development of the hypertensive disorders of pregnancy, particularly of pre-eclampsia.

Aim:

The role of common variants in ASC and related endophenotypes can be investigated using genetic association studies. While candidate gene association studies have identified a few variants that have been replicated, the majority of GWAS results have not been replicated (Berg and Geschwind 2012). Possible reasons for the failure of GWAS studies could be: 1) the high clinical and genetic heterogeneity underlying ASC; 2) the need for much larger sample sizes than previously thought; 3) The effect sizes of a single common variant is much smaller than previously thought, suggesting multiple epistasis. One solution to these problems is to test for genetic associations for underlying endophenotypes. Many of the underlying endophenotypes such as attention to detail, systemizing ability and empathy are quantitative traits present in the general population. Individuals with ASC are usually present at one end of the curve of these traits. Understanding which genetic variants, and by extension, which genetic and biological networks contribute to these traits will help us understand, in part, the variants that contribute to ASC. Due to the complex nature of these endophenotypes, a model-free GWAS would be the best approach to understand these traits. These studies must be sufficiently powered and must include a replication sample in order to be reliable. We have a number of different online psychological tests of empathy, attention to detail, systemizing, mathematical ability, and synaesthesia that are sensitive to individual differences in the general population and that are related to the autism phenotype. Many of them have a genetic component and are polygenic. We are interested in identifying the genes that show association with these traits.

Aim:

To systematically assess variation in the size, timing and frequency of consumption within a day, from day-to-day and across the lifecourse and how it relates to diabetes risk at 25 years of age and change in diabetes risk from 15 to 25 years of age.

Aims and Objectives

The aim of my project is to increase understanding of eating disorders (ED) and body dissatisfaction (BD) in adolescent girls from the perspective of population-level pathways.

Understanding whether ED and BD cluster in schools would inform the development of school-level interventions to reduce incidence of ED. No studies have investigated whether ED and BD cluster, despite the clinical observation that it appears to be the case, although disordered weight control behaviours do vary between schools. Preliminary results from the Swedish cohort described below suggest around 9% of variance in rates of ED is at school level.

To establish if early questionnaire data on frequency and form of stooling predicts future bowel and bladder dysfunction in children. This data will be ised to model the costs and benefits of treating infants and children for long periods with stool softeners to reduce the incidence of constipation, soiling and daytime wetting.