Proposal summaries
B3119 - Exploring the association between parenting self-concept friendship and mental well-being in adolescents - 07/06/2018
Early adolescence is the period in which self-identity may be challenged or reconsolidated by puberty onset, increasing importance of peer relationships and increasing conflicts between parents and children. Obviously, parents and peer have direct impacts on childrenâs development (Bronfenbrenner, 1992) and it is important to take parenting and peer relations into account when investigating children self-identity development and psychological wellbeing.
Previous research has shown that parenting was positively related self-concept and involvement in peer relations (Dekovic & Meeus, 1997), and parenting and friendship quality had the longitudinal effect on internalizing symptoms in early adolescents (Gaertner, Fite, & Colder, 2010). Also, having a clear self-concept was positively associated with adolescentsâ interpersonal relationships such as child-parent relationship and friendship quality (Becht et al., 2017) and mental well-being (e.g., Cross, Gore, & Morris). However, it is currently less well understood how parenting influence the trajectories of self-concept development, peer relations and mental well-being in adolescence and how parenting in early childhood and self-concept and peer relations in early adolescence together contribute mental well-being in late adolescence. Also, though parenting, self and social relationship are important to development, there is few evidences to show which stage, childhood or adolescence contributes more to child development.
B3115 - Gamechanger National Study of Cognition Using Digital Biomarkers - 24/05/2018
In 2017, prevalence of Alzheimerâs Disease (AD) was close to 50 million individuals, with this number predicted to double in the next 20 years. Importantly, the neurodegenerative processes associated with AD precede diagnosis by more than a decade, offering a critical window for preventative treatments. An ongoing challenge is how to best identify individuals in the clinically âsilentâ stage of this disease.
Smartphones offer a unique opportunity for detecting early cognitive (i.e. thinking) and behavioural change. Traditionally cognition is assessed using pen-and-paper tests completed within a 20-minute clinical appointment. Smartphones have the advantage of being able to measure cognition remotely and frequently over dynamic time frames; for example, memory can be tested over a duration of days rather than minutes. In addition, smartphone sensors enhance sensitivity by using touch, audio, video and movement sensors to measure behaviour. Mezurio, a smartphone application (app), has been developed in a collaboration between the University of Oxford and industry (Roche and Eli-Lilly pharmaceuticals). Intended to be freely available, Mezurio contains a selection of tasks specifically designed to measure the processes first sensitive to change in AD.
The GameChanger study, ran in collaboration with the UK Alzheimerâs Society, will establish the profile of performance on tasks contained within Mezurio across a wide demographic of the adult lifespan. By establishing what âhealthyâ cognition looks like, future research will be able to more effectively use the app to detect individuals showing early signs of cognitive impairment. In addition, GameChanger is working in close collaboration with UK-based research projects (The Avon Longitudinal Study of Parents and Children (ALSPAC), Generation Scotland, The Exeter 10,000, NIHR BioResource and UK Biobank). Volunteers who have already provided data to an existing research project will be able to enhance the value of their GameChanger participation by allowing us to link the data collected by the two research projects. This will allow us to further explore how factors associated with how well we age cognitively, for example genetics (specifically which copies of the APOE gene a volunteer carriers), health and lifestyle, influence performance on the Mezurio app.
Invitation to participate in GameChanger is public; any adult with access to an Apple or Android smartphone will be able to download the Mezurio app onto their personal device. Mezurio will prompt participants to complete daily tasks for a few minutes each day, for a month. These tasks may ask participants to: a) Learn associations between photos and arrow directions, b) Make similarity/dissimilarity judgments on groups of objects, c) Follow rules to move through sequences, d) Narrate and retell short comic strips aloud, e) Navigate through virtual mazes, f) Crack sequences of simple codes. In addition, volunteers will be asked to rate their mood and sleep each day. As a further optional component of GameChanger, participants can allow the app to passively collect data on their physical activity (movement and approximate location) during a 7-day lifestyle assessment. Each September for the next 2 years, GameChanger will ask participants to repeat the monthâs activity. This will allow us to study change in cognition over time.
B3112 - An investigation of the association between substance use in adolescence and mental health using linked data - 24/05/2018
Adolescence is a period of rapid biological and social change. The use of recreational substances, including alcohol, tobacco and cannabis, is widespread among adolescents. For some, adolescence and young adulthood are also the time when mental health difficulties emerge. This co-occurrence of substance use and mental health problems has attracted much research attention as to whether there is a causal link.
ALSPAC, like all longitudinal studies, suffers from attrition (over time, people drop out of the study) and non-response (those still engaged with the study may not complete every questionnaire, or every question within a questionnaire). If the likelihood of participating in ALSPAC is associated with substance use and mental health, analysis could lead to incorrect estimates of the association between them.
Linkage to administrative and health records is one approach to deal with attrition and non-response. In this proposed project, we plan to use data on mental health from participants' health records (e.g. GP records and hospital admissions) to investigate the association between self-reported substance use in adolescence and diagnosed mental health difficulties, particularly depression, anxiety and psychosis.
B3107 - Mental health of young people who stutter - 29/05/2018
It has long been believed that stuttering is associated with poor mental health. At one time it was thought that an anxious temperament was a cause of stuttering, but more recent evidence suggests that anxiety and other mental health difficulties are a result rather than a cause of stuttering; for example, children who stutter often experience negative attitudes and even bullying from other people, and such experiences can lead to mental health problems such as anxiety and poor self-esteem. Few studies have used community samples to look at the association between stuttering and mental health problems. ALSPAC is a particularly appropriate resource for exploring such questions, because unlike other similar studies, speech and language therapists checked for stuttering when the cohort members were 8 years old. In this study, we will look at whether and how mental health difficulties emerged in children who stuttered at 8 years as they grew into adolescents and adults. Since not all people who grow up with a stutter end up with serious mental health problems, we will also try to identify factors that are associated with positive mental health in people who stutter. We will also gather new data from the cohort members, to find out about stuttering in adulthood and its relationship to mental health. We will ask participants to complete a screen for common mental health problems and a separate measure of social anxiety, which is often elevated in people who stutter.
B3105 - Neuro-developmental outcome after anaesthesia in early childhood an observational study using ALSPAC - 24/05/2018
All the commonly used drugs that produce general anaesthesia have been shown to increase brain cell death in young laboratory animals and lead to abnormal function later on. Mounting concern about the potentially toxic effects of anaesthetic drugs on the young brain has led to 76 studies since 1990 which have attempted to measure the brain development and functioning of humans who were given general anaesthetics for surgery or procedures in early childhood. Aspects of brain development which have been examined include measures of intelligence, movement and co-ordination, behaviour, language and speech, literacy and numeracy. Other measures have included academic achievement in school and diagnoses of learning disability, autism and attention deficit hyperactivity disorder (ADHD). Unfortunately, these human studies are frequently of limited quality, with: too few children (on average 130 cases), no method to account for other causes of adverse brain development which could bias the results, no information on the duration and type of general anaesthetic drugs given and not specifically designed to assess children's brain development. Their results are conflicting and somewhat difficult to interpret. At present, it remains uncertain whether anaesthetic drugs are harming young childrens' brains. The definitive results of a single clinical trial specifically designed to address this important question are not due for several years. In the meantime, the number of published review articles, commentaries, consensus statements and statements by regulatory bodies continues to grow. The United States Food and Drug Association urges careful consideration of the risks and benefits of a general anaesthetic in young children and pregnant women undergoing anaesthesia which may last longer than three hours or require multiple procedures.
Our project will determine whether there is evidence of impaired long-term brain development in ALSPAC data, specifically those children who had general anaesthetics for surgery or procedures before the age of four. We anticipate that the detailed information recorded about these children and their parents, as well as the quality of assessment of their brain development throughout childhood and adolescence, will allow us to better investigate this important issue than previous human studies have been able to do. We also propose to collect new information from childrens' medical records in order to describe the types and duration of general anaesthetics which were given in the early 1990s for different surgeries or unpleasant procedures. This will help us to determine whether increased duration of anaesthesia is associated with additionally worse brain development, and will allow us to place the findings of the ALSPAC study in context with changes to paediatric anaesthetic practice in the last two decades, as well as enhancing the utility of the ALSPAC resource to future anaesthetic research.
B3103 - Decsription of blood count data and associations of adiposity and insulin with blood counts - 08/05/2018
People who are at an increased risk of thrombosis (clots) are often given antiplatelet drugs such as clopidogrel and prasugrel. These drugs work by reducing the activity of platelets, thereby reducing the risk of clots forming. It is understood that obese and diabetic people have more reactive platelets than healthy people. These subgroups of people therefore have an increased risk of having a heart attack or a stroke, even if they are taking these antiplatelet drugs. The processes that lead to this increased platelet reactivity in obese and patients with diabetes are unclear. This project aims to determine whether there is an association between BMI/insulin and increased platelet reactivity in young adults and to identify potential causes of this increased reactivity.
B3101 - Association between the complexity of written language in childhood and adolescent mental health - 14/06/2018
Concrete thought, expressed as concrete language, is a feature of psychotic illnesses. At present it is not known whether concrete language and thought precede the illness and are present at all points on the psychosis spectrum, from clinical disorder to psychotic experiences in the general populations. Previous work on ALSPAC data has investigated the association between parent report of child's language complexity and not found an association with later psychotic experiences. A collaborator from the Tokyo Teen Cohort has found an association between less complex written language in childhood and later psychotic experiences. It would be useful to investigate the same question in a language with a different structure from Japanese.
B3102 - Birth Cohorts and the Biosocial ethnographic interventions on the life course - 29/05/2018
Studies that follow individuals across time, taking a âlife courseâ approach, are important for understanding how biological and social experiences interact to shape health. However while biological, epidemiological and quantitative social science approaches are often used, incorporating lived social realities into a âlife course approachâ remains a neglected, yet vital resource for increasing knowledge about how health is shaped by biosocial processes. This 12 month pilot study will work with two high profile regional birth cohort studies in the UK and Brazil (ALSPAC and the Pelotas Birth Cohort) to explore how one in-depth method, ethnography, can be used to provide a richer understanding of social realities in life course approaches. It will focus on how ethnography can be used to examine a particular period in the life course, âmotherhoodâ and experiences of social adversity among birth cohort participants. Contributing innovatively to the development of a âmixed methodâ approach the pilot study will be a first step in making ethnography an essential tool in biosocial life course research by widening a discussion between disciplines about how understanding lived social realities and experiences can be more productively linked to biology or epidemiology.
B3100 - Peer victimisation during adolescence and its impact on wellbeing in early adulthood - 31/05/2018
Understanding mental illness is a pressing area of research with the ultimate aim of helping individuals to remain mentally healthy across the life course. This study aims to explore factors that influence mental health and wellbeing by considering the role of bullying. Bullying by peers sometimes leads to later mental health problems. Our study will consider how bullying during adolescence can affect an individualâs mental health and wellbeing during adulthood. Wellbeing is a concept that encompasses positive states like happiness, optimism and life satisfaction. Helping to understand how wellbeing is affected by bullying will improve our understanding of how individuals can still flourish despite negative experiences.
B3089 - Does childhood obesity hinder human capital development - 11/04/2018
The proposed project will address an important set of research questions on the social and economic impacts of childhood obesity by leveraging some of the most detailed longitudinal data sources available in the UK as well as innovative approaches to assessing causality and the links between health and social outcomes. It will do so with a view to making an impact on the actins of key stakeholders involved in addressing the problem. In particular, the study will rely on two national cohort studies reflecting the lives of individuals born in 1958 and 1970, and on a local cohort study of children born in 1991-92 providing a unique set of information based on biomarkers, anthropometric measures, linkages with rich administrative data, along with more traditional survey questions. The study will leverage biomarkers in the latter cohort and genetic information in all three cohorts in a detailed investigation of the causal pathways that link children early life exposures and background socioeconomic status to their likelihood of developing obesity in young age, to the social and economic outcomes associated with childhood obesity. In particular, the study will focus on dimensions of human capital (education and cognitive skills) and returns to human capital, in the form of employment and earnings, as well as forms of civic participation and social engagement.
B3085 - Replicating methylomewide findings from a developmental study of childhood trauma - 03/08/2018
By age 16, close to 2 children in 3 have suffered at least one adverse experience such as parental death, life-threatening illness, or family violence. Adversities have been robustly linked to psychiatric and other medical conditions where the consequences can persist far into adulthood. It is not well understood how early adverse experiences are biologically embedded and what processes might be set into effect that would sustain long term health risks. To address these key questions we performed a prospective, longitudinal methylome-wide association study (MWAS) of childhood adversity where data on adverse experiences was linked to methylation data on almost all 28 million common methylation sites in blood. Specifically, we used samples from the Great Smoky Mountains Study (GSMS). The GSMS started at Duke University about 25 years ago when participants were 9- to 13-year-old and continues today as the participants are in their 30s. The methylome was assayed using and optimized lab protocol for methyl-CG binding domain sequencing (MBD-seq).
Results showed that childhood adversity has a substantial impact on the methylome. These effects tended to increase with the number of adverse events and were predictive of future health outcomes. For example, using k-fold cross validation to obtain an unbiased estimate of the effects size, lifetime cumulative adversity exposure shared over 20% of its variation with the methylome. This adversity associated methylation variation in childhood (14.2 years of age) was a better predictor of depression symptoms in adulthood (25.8 years of age) then childhood depression symptoms themselves and this contribution remained significant after regressing out the cumulative adversity exposure count. Cell type specific MWAS suggested that most of the methylation changes involved the granulocyte cell subpopulation.
As a next step we propose to replicate findings in samples from the Avon Longitudinal Study of Children and Parents (ALSPAC). The ALSPAC study is critical for this purpose as, similar to GSMS, samples are available before and after adversity and where adversity induced changes can be linked to an array of health outcomes later in life. Furthermore, as ALSPAC is also a prospective, longitudinal it allows us to create a cumulative (life time) measure of exposure to adversity. As the vast majority of our top findings are not assayed by Illumina methylation array that cover only 450,000 sites (~2% of all common methylation sites in blood), we propose a targeted replication study using a protocol for amplicon sequencing of bisulfite converted DNA that we have already optimized and tested.
Successful completion of this project implies that we gained insight into how childhood adversities alters the methylome and what changes persist over time. We will also have identified processes associated with health risks in childhood/adulthood and found replicable methylation biomarkers associated with these risks. Methylation markers are stable and can be measured cost-effectively in blood, which is relatively easy to collect. Our findings therefore also have translational potential as, for example, diagnostic âbiomarkers of health riskâ.
B3084 - The effect of preterm birth on later renal health - 05/04/2018
As kidneys continue to develop up to 36 weeks of gestation, preterm infants are often born with reduced nephron numbers and consequently sub-optimal renal performance. Detailed research has been conducted examining kidney function in preterm neonates soon after birth, but few follow up these patients past infancy. Those that have measured renal performance in childhood and early adulthood have yielded varying conclusions. Further research exploring this topic is therefore required.
Serum creatinine and albumin are markers for kidney function. This study aims to compare the titres of these substances in individuals who were born prematurely and at term at various timepoints throughout their life.
As premature birth is becoming more common in the UK and worldwide, it is important to understand its possible implications on health later in life.
B3077 - EpiGenetics of Puberty and Risky Sexual Behavior - 27/03/2018
Pubertal development is a significant transitional process for adolescence as they move into reproductive maturity. This transition may also come with significant negative health and psychosocial consequences, however. Because early puberty has been linked to an array of health-related issues, factors that predict pubertal development differences among adolescents has been the focus of considerable research. One family factor that has been reliably linked to pubertal development, particularly girls' age at menarche (AAM), is father absence. Whether father absence causes differences in AAM is currently being debated by researchers. On one hand, some research suggests that father absence is an environmental influence that causally regulates AAM. On the other hand, some research suggests that the association is due to genetics: Genetic factors that might dispose a father to be absent are passed down to their daughters, which may dispose them to earlier AAM. This research is limited, however, in that both perspectives take a genes versus (or plus) environment approach, which overlooks how genes and environments operate together. The purpose of this proposal is to examine gene-environment interactions and epigenetic mechanisms of the relation between father absence, pubertal development, and related risky sexual behaviors in adolescent boys and girls.
B3079 - Exploration of associations between smoking topography and DNA methylation signatures - 04/04/2018
We have recently conducted a detailed study of smoking behaviour in young people, recording and measuring the number of cigarettes smoked, the number and duration of puffs taken, and the volume of smoke inhaled per puff/cigarette. We would now like to identify molecular markers of smoking behaviour in saliva. Although saliva cotinine levels accurately indicate recent nicotine intake, it does not capture long-term exposure or different smoking behaviours that are likely to impact on disease risk. DNAâ¯methylationâ¯is known to be an extremely stable and sensitive marker of smoking status that is predictive of smoking-related disease risk. It has also been used with some success to detect prenatal smoke exposure, own smoking pack-years and time since cessation. Several of our study participants are ALSPAC participants who recently provided saliva samples in the most recent ALSPAC clinic. We would like to use these samples to generate DNA methylation profiles in order to examine the extent to which detailed smoking behaviours are reflected in DNA methylation patterns.
B3074 - Exploration of functional links between sclerostin and phosphate metabolism - 17/07/2018
The level of phosphate in the bloodstream is regulated by a number of hormonal factors including klotho. These are stimulated in conditions such as impaired kidney function, which causes a rise in circulating phosphate levels. It has recently been found that when kidney function is impaired, another protein, sclerostin, is also increased. Sclerostin, which has an important role in regulating the amount of bone formed, is the target for a new treatment being developed for osteoporosis, acting by blocking sclerostin activity. Combined with other circumstantial evidence, we propose that important functional relationships exist between the hormones that regulate phosphate levels and sclerostin, which contribute to the decline in bone density seen in renal impairment. This hypothesis will be examined by exploring relationships between klotho levels, measured as part of this proposal, and sclerostin, in a sample of ALSPAC mothers.
B3076 - GlycA as a novel biomarker linking bacterial-mediated inflammation to adverse cardiometabolic/vascular traits in the young - 17/04/2018
Inflammation is a temporary protective process activated by the body to fight infection. If this response remains active for too long, however, it may cause changes within the blood and arteries that increase the risk of cardiovascular disease. Some teenagers and young adults already show signs of these changes, but why this happens isnât fully understood. As inflammation is known to be a response to infection, one explanation may be that it occurs in some people because they are more frequently exposed to illnesses/infections than others. Another explanation, however, may be that lifestyle choices that some people make (eating a poor diet, not exercising, becoming obese, etc) affect the âgood bacteriaâ that live within the gut, and that this triggers an inflammatory response from the body to try to protect itself. We aim to test whether bacterial-driven inflammation can cause changes in the blood and arteries that are often observed in people of this age. We also aim to test whether a newly discovered molecule (GlycA) is associated with these changes, and if having a high level of GlycA can therefore predict who is more likely to have cardiovascular problems 6-7 years in the future.
B3068 - To quantify age-related clonal hematopoiesis in pediatric-young adult samples - 25/07/2018
The overall goal of this project is to quantify age-related clonal genetic diversity (clonal hematopoiesis) in the blood/marrow of healthy population from age 0 (birth) to age 30.
B3066 - Investigating the genetics of post-traumatic stress disorder associated with pregnancy and birth complications - 15/03/2018
Post-traumatic stress disorder (PTSD) can arise from pregnancy and birth complications. PTSD followed by pregnancy complications has received attention from large epidemiological studies. Previous epidemioloigcal studies report ~6% prevalence of perinatal PTSD. Although genetic factors confer vulnerability to PTSD, there are no studies analysing the genetic variants that confer vulnerability to PTSD after pregnancy complications. This project seeks to examine whether the genetic and non-genetic risk factors influencing PTSD arising from pregnancy related complications are shared with those influencing PTSD arising from violence and disaster events and from other psychiatric disorders.
B3051 - The role of a SLC30A2 variant modulating zinc homeostasis in childrens growth - 16/02/2018
B3064 - Core Support for TwinsUK Cohort - 06/03/2018
This proposal does not seek access to ALSPAC data, rather it proposes uses a clone copy of some of ALSPAC data processes and infrastructure in order to support the TwinsUK cohort. The processes and infrastructure in question relate to ALSPACs Data Linkage activities and the PEARL Data Safe Haven - the ISO27001 certified policies, procedures, infrastructure for the capture, processing and subsequent analysis of linked 3rd Party routine records with study collected data. Equivalent TwinsUK research and study administration needs would be managed by the PEARL team. ALSPAC and TwinsUK data would remain distinct through this time.