This project will establish a network in which social scientists, geneticists and epidemiologists work together to better understand, and benefit from, longitudinal birth cohort studies, which follow participants throughout their lives, often including multiple generations. These studies are becoming more important in disease research, to understand how environmental factors affect our health. So far, social scientists have not played a prominent role in the design or implementation of this type of study. The input of social scientists is important to better understand the relationship between biology and society emerging from birth cohort studies. This project will fill this gap by creating a network of scientists from all disciplines, including the social sciences. The project will include longitudinal birth cohort studies in the Global North and also in the Global South, where little research has been carried out on how these studies work, how they are maintained and used.

There is substantial evidence demonstrating that in addition to the well-established link between exposure to childhood trauma and Posttraumatic Stress Disorder, PTSD has been associated with an increased risk for other severe psychiatric disorders such as psychosis. Individuals with psychosis have been found to have higher comorbid rates of PSTD compared to the general population (30%-50% vs 7%-9%). Importantly, the link between psychosis and PTSD is complex and multifactorial. There is very little knowledge on what could explain the high comorbidity between PTSD and psychosis, and more specifically the mechanisms/pathways that may explain why trauma may lead to psychotic symptoms, PTSD or to a combination of both. To date, the literature has focused on two main hypotheses: a) PTSD stands as a mediator of the relationship between childhood trauma and psychotic symptom severity. A model of continuity has also been suggested, implying that psychotic symptoms would be an exacerbation of the PTSD symptoms and b) PTSD and psychosis are both part of a broader spectrum of reactions to trauma with similar explanatory mechanisms at the level of cognitive schemas (e.g. beliefs about self and others), attributional styles and dissociative processes. There is a paucity of empirical evidence evaluating either of these hypotheses. Examining clinical and cognitive profiles of adults with psychotic experiences, with and without preceding PTSD (after childhood trauma) would be the first step towards disentangling complex relationship between the two disorders.

Our team is interested in variables that influence the weight gain patterns of young children. In this study we aim at identifying genetic variants (differences in the DNA between individuals) that could be used to predict which children are most at risk at developing childhood obesity. With this information we could identify children who would benefit most from early life obesity interventions.

Children, particularly daughters, of mothers who have been victims of sexual violence and abuse have a higher risk of becoming victims of sexual violence and abuse, compared to children of mothers who have no such victimisation histories. The majority of studies examining this intergeneration 'transmission' of sexual abuse and violence have been conducted using samples from populations in which there are a high number of victims and outside the UK. Furthermore, studies have tended to focus on the sexual abuse histories of the mother and not the father. This study, using a general population sample (i.e., of people not specifically identified on the basis of being victims of sexual abuse) will enable us to identify the extent to which mothers' sexual abuse experiences increase the risk of similar victimisation in their children. We will also examine the impact of the sexual histories of fathers and what other factors (e.g., other types of abuse experienced by the mother and/or father, parents' mental health, children's early development and conduct disorders) exacerbate or reduce the risk of intergeneration transmission.

Puberty timing has been decreasing for several decades. Earlier puberty is thought to be associated with greater cardiovascular disease risk. The aim of this project is to examine the association between puberty timing and cardiac measures at age 25 years.

I met with Dr Fanny Kilpi following her presentation on some of the maternal data with cognitive outcomes from ALSPAC. Dr Jon Heron noticed the similarity in terms of structure of her dataset and wondered whether we could use these data to trial a new method of handling data produced from another study that we are involved with called cVEDA.

The purpose of this exercise is to trial a method/s of dealing with data including missing data that is completely new to me and the cVEDA (Indian cohort) team. It is purely for learning purposes and to consider any assumptions and adjustments we may make to our models when our final dataset is officially released at the end of 2020 i.e. a practice dataset.

Despite a publishable manuscript not being our primary goal it would be useful to have some input into how best to use these data, and which exclusions to make (e.g. HRT etc). Also, we may discover the analytical approach to be useful to you and then a publication may result if all collaborators consider this a worthwhile exercise and outcome.

Problematic alcohol use is a serious public health threat. Research suggests that there exist unique, biologically-based "types" of adolescents who are at high risk for problematic alcohol use. Discovering these types will help us identify personalized prevention targets for this condition. This proposal will examine patterns by which adolescent risk factors for problematic alcohol use (conduct problems, depressive symptoms, and personality traits) are inherited to identify new highly heritable traits. This proposal will also test sex differences in these new genetically-based traits and their relation to problematic alcohol use to shed light on whether differing treatments are needed for males and females.

Polycystic ovary syndrome (PCOS) is a common disorder affecting women associated with major adverse health outcomes including subfertility and increased risk for type 2 diabetes. PCOS is a complex genetic trait which arises from a combination of genetic risk and environmental such as obesity. Currently, a conclusive diagnosis of PCOS cannot be made until sexual maturation is complete and the patient develops the characteristic diagnostic features of hyperandrogenism, oligomenorrhea, and/or polycystic ovarian morphology. However, studies in girls with increased risk for PCOS, including daughters of affected women and girls with obesity, have identified early reproductive and metabolic features of the syndrome even prior to the onset of puberty. Investigations into the early origins of PCOS have been limited by small sample size and lack of longitudinal data. The ALSPAC cohort includes critical data needed to investigate PCOS, including maternal reproductive histories, hormone levels, and offspring pubertal development, reproductive hormone levels, and menstrual histories. These proposal seeks to identify early clinical and genetic predictors of PCOS. Data collected in this project will be used for preliminary data in planned future innovative investigations of the early origins of PCOS. This study will propose using a translational approach integrating whole genome sequencing, epigenetic, and metabolomics data available in this cohort with clinical predictors of PCOS. This proposed research will have a sustained and lasting impact on the field as it will inform future efforts toward development of targeted prevention and early treatment approaches in at-risk girls.

Medical research in the UK is still hindered by a perceived lack of suitable data and sample resources that can be used by the research community. This perception contrasts starkly with the knowledge that there are hundreds of potential resources that can supply data and samples. The work of the Tissue Directory and Coordination Centre and backed by the Medicines Discovery Catapult has shown that the actual problem experienced by both academic and commercial researchers is the inability to find suitable resources. The consequence is that researchers tend to utilise the resources that are close by proximity (because they can go and talk to the resource directly) rather than close to their research goals. This approach is driven because there is no easy mechanism in which to discover other potential national resources.
The Tissue Directory and Coordination Centre (TDCC) is the UKs national centre that is tasked with coordinating biobanks (samples and data) to ensure that researchers re-use existing resources before seeking to collect new samples or datasets. TDCC is a joint endeavour between the University of Nottingham and University College London. TDCC has created a Tissue Directory to allow a high-level search on aggregated meta data that works well for clinical and disease orientated biobanks. In part the Tissue Directory has begun to solve the issue of findability but the challenge has evolved. Researchers can search on very high-level classification of disease, gender and age and resources matching those criteria are displayed. This Directory acts as a first filter but does not allow researchers to ask detailed feasibility questions. Although candidate resources are listed the confidence that the data or samples required do actually exist remain low once sub-typing is considered. Assuming the identified resources have a search portal (many do not), the researcher would have to create accounts in each in order to perform a more detailed search. This effort can often go unrewarded as the ultimate answer is often that once more detailed criteria are added, the resource does not have the data or samples required.

It is clear that in order to support and utilise existing UK investment in health care resources we must have a more efficient mechanism in which a researcher can ask a relatively detailed question and understand whether resources exist that could support them. It is especially important that researchers find out quickly if something is not feasible (rather than investing time and finding it is not) and equally that referrals to the resources (such as ALSPAC) from the search system does not create irrelevant traffic. By bringing together key academic, technology and research infrastructure stakeholders we are seeking to change this to make the necessary change.