We propose undertaking new data collection and analysing existing data to address the following research questions relating to self-harm in ALSPAC: 1.) What are the health and educational outcomes in children reporting self-harm with and without suicidal intent at ages 11 and 16. 2.)What is the influence of a) help-seeking, b) exposure to self-harm in friends and family, c) autobiographical memory, d) personality traits such as impulsiveness e) media/Internet exposure and f) non-suicidal self injury in mediating progression from suicidal thoughts and non-suicidal self-harm to suicide attempts from age 11 to 16 and from age 16 to 18. 3.) What are the differences and similarities between people who attempt suicide and those who carry out acts of NSSI without suicidal intent. 4.)Through the 5% subset of ALSPAC participants linked with the General Practice Research Database (GPRD) and the recent linkage of ALSPAC to Hospital Episode Statistics, determine the reliability of self-report self-harm and investigate the impact of non-response bias on observed associations. We propose undertaking the following analyses: 1.) Prospective analysis to estimate the incidence of self-harm at age 21. 2.) Prospective analysis based on the self-harm questions at age 11, to identify health and educational impacts of self harm at this age and progression of suicidal thoughts and act between ages 11 and 16. 3.) Prospective analysis based on responders to the self-harm questionnaire at age 16/17. We will assess the impact of self-harm reported at age 16/17 on mental health (CIS-R), educational and other social outcomes by age 18-21. We will compare outcomes for those participants who self-harmed with and without suicidal intent. 4.) We will conduct further prospective analysis to identify social, psychological and educational predictors of self-harm at age 16/17 and 21. 5.) We will explore the reliability of self-report self-harm and investigate the impact of non-response bias on observed associations by identifying a) whether episodes of self-harm identified through HES and GPRD linkage were reported by participants, b) rates of self-harmamongst non-responders to clinics/ questionnaires.

Some of the most important studies of people's lives in the UK, including the University of Bristol Children of the 90s study (ALSPAC), will be brought together in a national centre of excellence thanks to a £5 million project launched this week by the Economic and Social Research Council (ESRC) and the Medical Research Council (MRC).

The Cohorts and Longitudinal Studies Enhancement Resource (CLOSER) project will enable research-ers make better use of the data from nine of the country's leading studies with participants born as early as 1911 and as recently as 2007.

The UK is home to the largest and longest-running longitudinal studies in the world, this world-leading initiative will pay a vital role in maximising the use, value and impact of these studies both within the UK and abroad.

Professor Jane Elliott from the Institute of Education in London will lead a team to establish the na-tional centre of excellence across the nine longitudinal studies. ALSPAC will be represented by its ex-ecutive director, Lynn Molloy and its head of laboratories, Dr Sue Ring.

Strengthening the links between these studies will allow researchers, policymakers and others to make much better use of the rich and detailed data on people's lives gathered over many years in the UK. Repeating the same longitudinal analysis across a number of studies allows researchers to test whether results are robust, and how they are changed by the context in which data has been collected.

Cross-cohort analysis helps the understanding of changes in society and how policy impacts on peo-ple's lives. For example, understanding the background to issues such as the rise in obesity and the stagnation or decline in social mobility requires longitudinal data collected from several generations of people.

A major element of CLOSER will be a single tool that enables researchers to find the information they need for their analyses across all the cohort and longitudinal studies involved. The search platform will be designed for use by a wide range of users with very different levels of experience in data manage-ment, analysis and discovery. It will provide a simple, intuitive interface, encouraging more researchers to use longitudinal data and thereby stimulating interdisciplinary research.

CLOSER will also offer a programme of training which will enable a whole new generation of re-searchers and policymakers to use these rich and complex longitudinal data to help inform key areas such as education and health. It is a £5-million initiative over five years and part of the larger £33.5 million Birth Cohort Facility Project which includes the new birth cohort study - Life Study.

The Universities and Science Minister, David Willetts, said: "Cohort studies give unparalleled insights into people's lives and their life chances. This excellent new facility will make that easier than ever before."

Lynn Molloy, Executive Director of the University of Bristol's ALSPAC, said: "CLOSER is a fantastic opportunity for UK-based cohort studies to work together to better utilize the research arising from these studies. I am delighted that ALSPAC is involved in this groundbreaking project."

Professor Elliott, Director of the Centre for Longitudinal Studies, added: "I am delighted to be given this opportunity to lead this pioneering initiative which will help researchers to address key questions - for example about the factors that are important for children's wellbeing, and about behaviours and experiences that influence health in later life."

We plan to examine the potential mechanism(s) whereby RSPO3 regulates the functional properties of adipose precursors and thereby regional adipose depot size and function. Manipulation of RSPO3 expression and/or activity to achieve a more beneficial pattern of fat distribution and/or modulate adipose tissue function offers an alternative approach to treat obesity associated cardio-metabolic complications.

To firmly establish the genetic association between RSPO3 and (a) waist-circumference (b) WHR and (c) metabolic profile we seek to genotype the entire OBB and replicate our findings in an independent cohort (mothers of the ALSPAC cohort). In order to achieve this we require ?50 ng of DNA (at 5-10 ng/mcl conc.) to genotype the 3 relevant SNPs. In addition we require anthropometric and biochemical data as described above.

Background: Rare monogenic disorders such as sclerosteosis have been reported to lead to an increase in bone mass, in association with abnormal facial features such as mandibular overgrowth (1). We have recently observed a similar association in adults identified within the population as having elevated bone mineral density (BMD) (2). More detailed analysis of this cohort of high bone mass subjects revealed increased thickness and circumference of cortical bone, which might conceivably also be related to growth of skull bones. Since facial growth is largely complete by age 15, particularly in girls, analysing associations between indices of face shape obtained in the ALSPAC cohort at age 15, and bone parameters ascertained at the same age, may shed important light on relationships between skeletal development and facial appearance.

Exposure variables: The primary exposure variables will be indices obtained from pQCT of the mid-tibia at age 15, particularly cortical thickness, cortical density, and periosteal circumference. Further exposure variables will include bone measures derived from total body DXA scans performed at the same time, including total body bone area and BMD, and skull area and BMD. Whether bone measures at earlier time points predict subsequent facial features will also be explored, based on total body DXA scans obtained at earlier time points.

Outcome measures: Facial shells, consisting of in excess of 40,000 points, have been generated in 4747 children in ALSPAC at 15 years of age, from which outcome variables for this study have been derived. These comprise 22 distinct facial landmarks, including the relative prominence (z-distance) of the pogonion, nasion and glabella, and thewidth (x-distance) of the chin and bridge of the nose.

We have four aims. First, to identify those children born to depressed mothers in the ALSPAC Study who would be classified as resilient on the basis of their scores on the SDQ in middle childhood. Second, to study the factors in early life associated with resilience in this group. Third to investigate the role of quality of early maternal care on development of resilience. Fourth, to identify those early factors involved in resilience which may be potentially amenable to intervention. Specific research questions / study objectives: 1.)When mothers are grouped on severity and duration of depression, what proportion of children born to depressed mothers are classed as resilient on the basis of the median total score on the Strengths and Difficulties Questionnaire (SDQ) administered at ages 8 and 11 by parents and teachers? 2.) Is this concept of resilience generalisable to other outcomes? How do resilient children, non-resilient children, and children of non-depressed mothers compare on other components of adaptive functioning measured when the children were ages 8 to 11 years? Do boys from the resilient group show a different pattern to girls? 3.) How do resilient children compare with non-resilient children and children of non-depressed mothers for the following factors: Exposure to major stressors, Quality of maternal care in the first year, Modifiable factors in the first year e.g. remaining with partner, relationship with partner, parental support, social support, neighbourhood characteristics, financial resources, breastfeeding.4.)Do the modifiable factors in 4 above act through altering the quality of maternal care in the first year or independently? Which aspects of quality of maternal care are important?

Given that the whole mitochondrial genome is involved in the synthesis of OXPHOS proteins, it is plausible that several rare variants could add together to compromise ATP production and thus contribute to human disease. We aim to test this hypothesis in several disease cohorts and to compare these data to the ALSPAC control cohorts. We will use NGS to determine the frequency of mtDNA variants present at MAFgreater than 1% in at least four diseases (Parkinson's disease, ischaemic stroke, sepsis and osteoarthritis) for which we have the strongest preliminary data, and then five additional human diseases where mtDNA variants have been implicated (hypertension, Type 2 diabetes, coronary artery disease, Alzheimer's disease, primary biliary cirrhosis), depending on the degree of pooling that can be reliably achieved. For each disease we will study 2000 cases, and compare the data to both control cohorts to identify 200 variants most strongly associated with each specific disease. We will use iPLEX Sequenom MassArray to individually genotype both the discovery and an equal-sized replication cohort for each disease. Individual genotyping of both the discovery and replication cohort will enable the analysis of haplotypes and/or clusters of potentially related SNPs, which is not possible for the pooled data. Our power calculation indicate that this experimental design will have greater than 80% power to detect an association at Pless than 0.0001 for a single allele at MAFgreater than 6% with a relative risk (RR) of greater than 1.6; at a MAFgreater than 1% for a RRgreater than 3

It is proposed to collect data on individuals' political views and social attitudes such as altruism, or trust and broad measures of personality characteristics. It is hoped that this will allow a first glimpse at how our early environment and genetics, combine with current circumstances to determine our beliefs. We propose asking questions similar to those below. Ideally, all questions would be asked of both parents and their children. The collation of data on social attitudes would also be extremely worthwhile in itself. Using forms of question that have been widely used in other surveys will facilitate comparability with other surveys/studies. 1. Measures of Political Ideology a. Left-Right Scale question similar to used in Eurobarometer/WVS/BSA ) b. Libertarian-Authoritarian Scale - BSA 2. Political Behaviour Questions, E.G: a. Did you vote in the last general/European/local election? If so who did you vote for? b. Do you feel that one party tends to represent your views at the national/European/local level? If so which? c. Do you belong to a political party, trade union, environmental organisation, etc.? d. Have you engaged in any of the following types of political action? Boycotts/ Petitions/Rallies/etc. .3. More fundamental questions about political beliefs - belief in the power of government (Can government be an effective force for good, is government necessary, taxation is justifiable, progressive taxation is justified.) 4. Trust. Generally speaking, would you say that most people can be trusted or that you need to be very careful in dealing with people? Thinking just about people you know, would you say that most of them can be trusted...5. Other Social Attitudes (Altruism, Inequality-Aversion, etc.) , Religosity6. Big 5 personality traits - 44 or 10.

The growth trajectory early in infancy and during childhood has been found pivotal in the early determination of adulthood metabolic health. In fact, early divergences from the normal growth curve at critical windows during infancy and later childhood are frequently associated with a higher incidence of obesity and impaired metabolic health in adulthood (Dietz WH, AJCN 1994). GWA studies have revealed several genetic variants associated with adult anthropometric measures such as weight and BMI. The main objective of this study to investigate whether phenotypes such as peak weight velocities (PWV) and timing of Adiposity Rebound(AR) derived from longitudinal data are associated with early adiposity (Sovio et al, PLoS Genet 2011). Since the effects of common variants on these traits are small or moderate, we propose a GWAS meta-analysis approach in the EGG cohorts that have both GWA data and frequent enough height and weight measurements available in infancy and/or middle childhood. The specific age window that will be considered: (1) infancy 0-2 years and (2) early childhood from 1.5-7 years. The phenotypes which are calculated are: peak weight velocity (PWV) in infancy, BMI and Age at Adiposity Peak (AP) and Adiposity rebound (AR). In ALSPAC, we propose calculation of PWV and BMI AP as it has data available on infant weight at birth, 6 weeks, 9 months and 18 months. The initial primary GWAS on 4 cohorts has been conducted within EGG and we have identified 8 SNPs reaching GWAS significance which are taken forward to replication stage within other available cohorts.

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