Proposal summaries
B3410 - Testing the role of relative age within school year on mental health in children with neurodevelopmental vulnerability - 24/11/2019
In England and Wales, the academic year begins in the September, and children start school in September before they are five years old. If children are born in September, then they are nearly five when they start school, but if they are born in August in the following chronological year then they have only just turned four years old when the school year starts. Studies have shown that the youngest children within a school year are at an increased risk for mental health problems, social impairment, neurodevelopmental disorder and intellectual disability diagnoses, and lower educational attainment (Bedard & Dhuey, 2006; Zoëga et al., 2012; Pottegård et al, 2014; Root et al., 2019). Cross-national comparisons of large representative population surveys that compare countries with different school entry dates have suggested that associations may reflect causal influences of age within school year on these outcomes, rather than season-of-birth (Goodman et al., 2003). This project will focus on children with early neurodevelopmental vulnerability, which will be defined using neurodevelopmental symptoms and diagnoses, genetic risk, or prematurity of birth. These children are all already at a higher risk of mental health problems including depression (Rice et al., 2018). We hypothesise that relative age effects may affect these groups of children more than others over development from childhood to adulthood. We also hypothesise that differences in mental health by month of birth will emerge only after school entry but show some persistence across the school years into early adulthood.
B3408 - International Cannabis Consortium - GWAMA of quantity/frequency of cannabis use - 14/11/2019
The International Cannabis Consortium has been created to combine the results of multiple genome-wide association studies of different cannabis use phenotypes (e.g., lifetime use, age at initiation, frequency of cannabis use) in meta-analyses in order to increase the probability of detection of genetic variants associated with individual differences in cannabis use.
B3407 - Identifying genetic variants predisposing to overeating behaviour - 10/01/2020
Obesity has been associated with a number of life threatening common diseases and is cited as the driving force behind poor health from early ages in both developing and developed countries. Obesity is the product of a complex interplay between our biology and our environment, with our behaviour playing a major role on how these interact. Previous studies have shown that targeted behavioural changes are effective obesity interventions for both short-term weight loss and long-term weight management. Although behaviour is a complex characteristic shaped by our culture, society and upbringing, similar to other complex human characteristics, it also has a genetic component that predisposes us to respond to environment cues in a specific manner. These genetic predisposition markers usually confer poor prediction of a specific individualâs complex phenotype or behaviour, but in larger population samples, they can provide information for existing patterns that can help us plan effective population level interventions and assess the causal patterns associated with them.
B3404 - Analysing the association between inflammation and scoliosis in a population-based birth cohort a proof of concept study - 11/11/2019
Scoliosis (spinal curvature) is an important condition that can be associated with pain and loss of function, but little is known about the causes of scoliosis. Previous work by our group using zebrafish, has shown that inflammation is one potential cause. However, the link between inflammation and scoliosis has never been examined in humans. We are proposing a project to do this using ALSPAC because data on inflammation and scoliosis has already been collected. Our research group consists of the scientists who originally identified inflammation as potentially important in zebrafish, plus the researchers who developed the method to measure scoliosis in ALSPAC.
B3405 - DNA methylation signatures of aggressive behavior - 11/11/2019
DNA methylation signatures of aggressive behavior may capture lifetime trait dynamics and environmental exposures. DNA methylation in peripheral blood is known to be associated with a variety of exposures (e.g. cigarette smoking) and traits (e.g. BMI). We propose to determine if DNA methylation is associated with aggressive behavior to better understand the biological correlates of aggression and to evaluate the potential utility of aggression biomarkers in peripheral blood.
B3406 - Acceptability to participants of novel data linkages ethical issues and the practicalities of obtaining consent Evidence from - 21/11/2019
This project will summarise and collate information gathered by ALSPAC and TwinsUK describing participant understanding and feelings towards 'novel' methods of data collection. This is in response to rapid changes in possibilities for data collection which are emerging from the rapid digitisation of routine information, that many people now routinely carry powerful computers (mobile phones, smart devices), and that many devices are now connected to the internet (e.g. smart doorbells and smart thermostats). There is potentially very valuable information which can be collected through either linking to individuals' records or by collecting the 'Digital Footprint' records left through using digital connected devices. In addition, these connected devices - e.g. mobile phones, or smart speakers - provide an opportunity to collect data in new ways.
It is vitally important that studies - such as ALSPAC and TwinsUK - understand participants views on this. This is so that studies can understand what is acceptable and what is not, what safeguards are needed to ensure acceptability, and how to inform participants about these new options and how they could work. This project is summarising existing information, it is not collecting any new information.
B3402 - Quantitative triangulation in aetiological epidemiology - 07/11/2019
We are developing methods for combining results across studies, primarily based on summary results (from published papers). We work within a framework known as 'triangulation', in which we compare and contrast results of studies that take different appraoches to answering the same underlying question. Where ALSPAC provides relevant data that can be compared with the findings from other types of study, we propose to analyse these. We will select topics in conjunction with external collaborators, ensuring the case studies address important research questions in aetiological epidemiology.
B3403 - Validation of alcohol score as a negative control - 07/11/2019
We are interested in understanding the effects of alcohol consumption on cardiovascular disease risk. To do this we have been constructing a genetic risk score in the UK Biobank study, which we wish to validate in ALSPAC as a negative control.
B3399 - Integrating longitudinal and cross-national evaluations of increased community alcohol availability and the health and economic - 08/11/2019
While the detrimental impact of alcohol use is well understood, in England and Australia, many adolescents consume, purchase, or are provided alcohol. In the short term, alcohol is linked to increased risk of injury and fatalities; in the long term it is associated with increased risk of cancers and diseases. Adolescent alcohol use is of particular concern as it is associated with poor mental health, brain damage, and increased risk of dependence in adulthood. Despite strong evidence that reducing the supply of alcohol in the built environment can be used to prevent or reduce consumption at a population level, in England and Australia, the prevalence of environments where alcohol is readily available is increasing yearly, often in low socio-economic urban areas.
The number of alcohol outlets in the built environment is one indicator of supply and availability. For adults, evidence consistently demonstrates an association between the number of outlets in a given area and alcohol-related behaviour. The evidence of increased availability on the health and well-being of adolescents is less clear and under examined. Most research is cross-sectional and USA-focused. The proposed project will address this important evidence gap. Our team will undertake a comprehensive longitudinal cross-national analysis of the links between alcohol availability and child and adolescent alcohol uptake with consumption, health and well-being over the adolescent and young adult years. It will use, high quality longitudinal studies of English and Australian participants followed over 17years (2002 to 2018) to examine links between changes in alcohol availability and alcohol-related behaviour and health from the school years (10-17 years) into early adulthood (27-31 years).
English data will be drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC) and Australian data will be drawn from the International Youth Development study (IYDS). Data will be merged with retail outlet data. Changes in the density of outlets in a participantâs local area and its link with the age of initiation and consumption will be examined. Limitations of previous study designs will be addressed by employing novel cross-lagged panel analysis techniques, which mimic an RCT and can be used to develop causal evidence with longitudinal data. Multi-level growth, elasticity, and latent class modelling will be used to investigate issues neglected in the international literature relating to development and policy. The core research questions will be: Does density exposure at early ages have a sustained effect on child and adolescent behaviour? How does density exposure affect the severity and breadth of alcohol-related problems of young people? Are there maximum and minimum availability levels associated with adolescent alcohol-related behaviour and health? Cross-national comparisons will be made and socioeconomic sub-group analyses will be undertaken. An economic evaluation of the impact of adolescent consumption on health and services will be completed. To assist with translation and impact an analysis of policy and legal barriers and facilitators associated with opening or opposing of new alcohol outlets will also be undertaken.
The hypotheses guiding this research proposal are:
1. Exposure to higher density of alcohol sales outlets will predict an earlier age of uptake (initiation of use) of alcohol by adolescents (10-17 years of age) and increases the risk and rate of progressing to greater alcohol use across adolescence and early adulthood.
2. Over time, changes in alcohol sales outlets will be associated with changes in the extent to which adolescents report illegally purchasing alcohol, and changes in the extent to which they report parents supply alcohol to them.
3. Increased costs (health and broader societal), lower productivity and poorer health (including mental health) are expected in adolescents who are exposed to higher alcohol outlet densities.
B3400 - Assessment of lung function decline in young adults identifying and characterising early expressions of COPD - 10/12/2019
Chronic Obstructive Pulmonary Disease (COPD) is commonplace affecting 10% of adults and causing 3 million deaths/year worldwide. It is characterised by poor lung function (airway narrowing), that is difficult to improve and is viewed as a disease of older smokers. However recent research reveals that several factors may influence lung function developmental patterns (trajectories) from early life towards COPD.
In our Isle of Wight Birth Cohort (IOWBC) at 26-years we showed that young adult asthmatics at 26-years experienced poorer adolescent lung growth, young adult smokers had faster declining lung function in adulthood while asthmatic smokers showed worst lung function suggesting particular risk for early COPD. Indeed several lung function trajectories are now described which might be associated with COPD. Confirmation of such associations is needed and best achieved using research cohorts studied across the lifetime.
We will identify lung function trajectories using measurements in the IOWBC to age 32-33 and a sample of 1500 subjects in ALSPAC-30 with the goal of identifying early evidence of COPD and what drives that. We will further characterise IOWBC participants using more detailed lung function tests, imaging (CT scans), and samples obtained directly from their airways using techniques called induced sputum and bronchoscopy to identify COPD features. They will also provide blood samples to assess relevance of gene/environment interactions to COPD-risk (epigenetics). We will test these IOWBC COPD-risk findings on a proportion of ALSPAC-30 subjects who will also undergo further lung function tests and imaging to see how generalisable they are to other populations. We will use existing ALSPAC-30 epigenome characterisation to further corroborate IOWBC findings.
B3401 - Associations between experience of sexual violence birth experience and perinatal mental health outcomes - 31/10/2019
We will use data collected by ALSPAC to explore whether the experience of prior sexual violence affects the birth experience and whether this, in turn, affects mothers' mental health and child attachment in the first two years after birth. Our general aim is to better understand how pregnant mothers experience maternity/obstetric services, and how such services might be improved for survivors of sexual violence.
B3398 - Predicting Childhood Language Disorder and Ability using Genome-Wide Polygenic Scores - 28/10/2019
Language is vital for social-emotional development during childhood and it is unsurprising, therefore, that language disorder is associated with a number of mental difficulties including symptoms of depression and anxiety. There is sound evidence for the heritability of language traits in children, but little is known about the specific genetic variants that explain this heritability. Identifying such markers will enhance understanding of the aetiology of mental health difficulties in those with language disorder and could inform early interventions designed to prevent adverse outcomes and improve quality of life in the most vulnerable children. The proposed project will assess the extent to which a number of different genome-wide polygenic scores (GPS) can predict language ability, including language disorder, in clinical and population-based samples.
B3397 - Religious belief health and disease a family perspective - 06/11/2019
Here we propose to investigate whether - and how - religious or spiritual belief /behaviour influences health (and vice versa).
The ALSPAC parents have answered data about their religiosity on several occasions. In combination with the information - both self reported and measures in clinic in both parents and their offspring - we will be able to answer questions such as: (a) is religious or spiritual belief and/or attendance (RBA) of adults associated with health benefits or disadvantages in the short or long-term? (b) Does the RBA of one or both parents influence the health of their offspring? (c) Are there differences in risky behaviours between participants reporting different RBA that may explain our findings.
B3395 - Emotional dysregulation self-harm and eating disorders a mechanistic investigation - 17/10/2019
As many as one in six teenagers have self-harmed at some point, and self-harm is the strongest known risk factor for suicide. Eating disorders are also common, affecting over one-in-twenty adolescent girls. Both self-harm and eating disorders are linked to early death.
Up to half of those with an eating disorder also self-harm. However, we know little about why these mental health conditions often occur together.
One reason might be that some risk factors for eating disorders and self-harm are the same. One characteristic, seen in both conditions, is difficulty managing emotions. However, we do not know whether individuals with an eating disorder find managing emotions difficult because they have an eating disorder, or whether difficulty managing emotions is one of the reasons they develop an eating disorder. Similar gaps in our knowledge exist in relation to people who engage in self-harm; we do not know for certain whether difficulties managing emotions occur before self-harming behaviour starts. One study in adolescents in China suggests difficulty in managing emotions leads to later self-harm, however, little else is known about this area. It is also likely that a number of other factors link difficulties in managing emotions with later self-harm and eating disorders. These factors include difficulties in understanding social situations, difficulties in reading facial expressions, and the experience of being bullied.
To enhance our understanding about the development of self-harm and eating disorders, we have assembled a team of outstanding scientists from two universities.
We will conduct an analysis of existing data from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC is a study of over 13,000 children born in and around Bristol in 1991-1992 and followed up since birth with regular questionnaires and clinics. Very few studies have such a large number of people, with such detailed questions collected over time. We will use ALSPAC data to study whether early childhood difficulties in managing emotions is associated with later self-harm and eating disorders. We will also use it to investigate whether ability to understand social situations, to recognise emotions, or the experience of being bullied, are involved in the relationship between difficulties in managing emotions and later self-harm and eating disorders
B3394 - Onset of menarche and depressive symptoms from adolescence to adulthood - 11/10/2019
During puberty, adolescent girls show a dramatic increase in depressive symptoms, and by mid-teens girls are twice as likely to have depressive symptoms compared to boys. It has been suggested that this increase is controlled by the timing of puberty and, in particular, the onset of menarche; girls who experience puberty earlier may be more likely to experience more depressive symptoms compared to girls who experience it later. Although this link is seen in girls in their mid-teens, it is not clear if this association continues into later teenage years and later on, into adulthood. It is possible that girls who experience late menarche have a decreased risk of depressive symptoms into adulthood and therefore this late menarche may serve as a protective effect. However, girls who experience late menarche may show a 'catch-up' effect and eventually have similar levels of depressive symptoms compared to girls who have an earlier onset of menarche. There is a lack of research investigating the onset of menarche on depressive symptoms beyond teenage years, into adulthood. It is therefore important to investigate whether onset of menarche and the timing puberty explains some of the depressive symptoms seen in adult women. This would also aid in the understanding of the mechanism behind the link between puberty and depression including psychosocial and, hormone and neurological theories.
B3392 - The interplay of maternal and fetal factors in mechanisms of fetal growth birth timing and related adverse outcomes - 18/10/2019
Maternal obesity in pregnancy is increasing worldwide and is associated with adverse pregnancy outcomes for both mother and baby. However, the risks are heterogeneous, with some obese pregnancies leading to preterm birth and reduced fetal growth, and others complicated by high birth weight. Some women who are obese may alternatively have uncomplicated, healthy pregnancies. There is an urgent need to identify those women and babies most at risk of specific outcomes and thus better target healthcare management and interventions. To do this, we first need to better understand the mechanisms underlying how maternal risk factors combine with the fetal response to influence risk. To date, our work using ALSPAC (project B2388) and other studies has identified genetic variation in both mother and baby that is associated with birth weight. We have used these genetic variants to investigate causal associations between maternal modifiable risk factors (e.g. blood pressure, glucose levels) and birth weight of the baby. However, many questions remain unanswered, including whether maternal blood pressure or glucose also influence the timing of birth, the weight of the placenta and the levels of insulin (a key growth factor) produced by the fetus. In addition, the role of the fetal response to the maternal environment is not well defined, and it is not known whether this fetal response influences maternal metabolism. This project will transform our understanding of the mechanisms connecting maternal BMI, glucose and blood pressure, fetal and placental growth, fetal insulin and the timing of birth, using large-scale genetic datasets. By clarifying these mechanistic relationships, the work will pave the way for the identification and targeted management of high-risk obese pregnancies.
B3393 - G1 Addition of lung function to G1 clinic 30 - 18/10/2019
Obstructive lung diseases are a common cause of disease and disability throughout life.
According to WHO estimates, 65 million people have moderate to severe chronic obstructive pulmonary disease (COPD). More than 3 million people died of COPD in 2005, which corresponds to 5% of all deaths globally.
In 2002 that COPD was the fifth leading cause of death. Total deaths from COPD are projected to increase by more than 30% in the next 10 years unless urgent action is taken to reduce the underlying risk factors, especially tobacco use. Estimates show that COPD becomes in 2030 the third leading cause of death worldwide.
The aim of this research project is to understand factors during childhood that influence the development of peak lung function in early adulthood. We will measure the lung function of around 5,000 young adults who have been intensively studied since before birth as part of a longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Lung function increases with physical growth through childhood, reaching a peak in early adulthood. Following this peak, there is a gradual loss of lung function throughout the rest of life. Therefore, failure to attain maximal lung function during childhood could lead to early onset of respiratory illnesses in adult life. This study will build on previous measurements of lung function in the ALSPAC cohort linked to a wealth of data on early lifestyle and environment to try to find out what factors are associated with slow acquisition of lung function during childhood and low peak lung function in early adulthood.
B3389 - An investigation of the environmental effect of parental genotypes on offspring behavioural problems - 08/10/2019
Parental depression is related to internalising as well as externalizing problems, including attention problems, in childhood. These behaviours are heritable, so this association may be due to the transmission of genes from parents to children. However, as parents also provide part of the environment to their children, it is difficult to disentangle the role of nature versus nature in the intergenerational transmission of these behaviours.
One way to investigate the extent to which parental environmental influences exert an effect on offspring behaviour is by looking at the impact of the parental genome. M-GCTA (maternal-effects genome-wide complex trait analysis) estimates the extent to which SNPs in the maternal or paternal genome contribute to variance in offspring behaviour.
Additionally, recent investigations have made use of polygenic scores constructed using non-transmitted DNA from parents to offspring to report associations between parenting and offspring behaviours traits. These studies show that the part of the parental genotype that children do not inherit nonetheless predicts childhood behavior, indicating an effect of genetic nurture. The methodology has not been applied to investigate parental influences on offspring behavioural problems thus far. The aim of this project is to use transmitted and non-transmitted polygenic scores to clarify parental genetic and genetically-mediated environmental influences on offspring internalizing, externalizing and attentional problems. Furthermore, we aim to investigate whether the genetic nurture effect on offspring internalizing, externalizing and attention problems is exacerbated in children of depressed parents.
B3391 - When Sleeping Like a Baby Isnt So Dreamy - 08/10/2019
Much of the "Motherhood Penalty" that tips womenâs wage trajectories lower than menâs trajectories has been attributed to time out of the labor market â either for maternity leave or because of subsequent scaling back of hours. We explore whether lost/interrupted sleep accounts for some of this penalty, either as a proximate cause for scaling back on hours or because of lower productivity upon returning to work.
A babyâs sleep may have lasting consequences on her parentsâ earnings if (a) sleep loss continues for several years, (b) sleep loss (of either short of long duration) leads to scaling back of labor force participation, or (c) sleep loss (of either short or long duration) produces worse work and bosses put outsized weight on post-leave work.
The project contains several testable hypotheses:
- Lost/interrupted sleep can account for some of the motherhood penalty
- Lost/interrupted sleep leads to decreased labor force participation
- Lost/interrupted sleep should vary inversely with duration of parental leave since baby sleep is often worse immediately after birth
- If lost/interrupted sleep is particularly important for creative/executive tasks, one may see greater portions of the motherhood penalty explained in jobs that use those faculties.
- The sleep penalty should be smaller if there is paternal/household help
B3390 - Predictors and patterns of self-harm thoughts and behaviours - 11/10/2019
Self-harm in young people is a major problem. As many as 1-in-6 teenagers have self-harmed, but we know little about what happens to them as they get older. We also know little about how much self-harm thoughts and behaviours (SHTB) change from day-to-day, and what factors help to predict this. This project will look at predictors and patterns of SHTB both over long periods of time (from adolescence to adulthood) and over short periods of time (over days/weeks).
Although selfharm is very common in young people, most do not seek help. This makes it difficult to provide support. In this study, I will find out whether young people who self-harm are either (1) not visiting a GP or (2) visiting a GP for other reasons and not telling them about their self-harm. I will also look for factors that will help GPs to better identify young people who have self-harmed.