Proposal summaries
B3416 - Investigating a DNA methylation signature of e-cigarette use - 29/11/2019
Electronic cigarettes (e-cigarettes) have the potential to reduce the harm caused by smoking, but there is currently little information regarding their long-term safety. We propose a novel methodology to quantify aspects of the biological (specifically epigenetic) changes associated with e-cigarette use, and the extent to which these changes are associated with future disease risk. We will determine whether e-cigarette users (âvapersâ) are more comparable to smokers of tobacco cigarettes or to never-smokers with respect to their epigenetic signature. We will then determine whether the epigenetic profile associated with e-cigarette use differentially predicts risk of disease, and whether these epigenetic changes are causally linked to disease, and as such may be targets for preventative interventions. This research will provide key scientific insights, as well as valuable information to both cigarette smokers and vapers regarding the relative safety of these products in relation to their biological impact and future disease risk.
B3414 - The Association between the Natural Environment and Emotional Social and Behavioural Development - 02/12/2019
Exposure to natural environments has been shown to be associated with child development and outcomes later in life. This will be investigated by measuring exposure to the natural environment using a combination of linked spatial environmental indicators and self-reported data. For example, normalized difference vegetation index (NDVI) measurements will be used alongside subjective measurements of parks visits and outdoor time. This will assess exposure multi-dimensionally, by measuring how much an individual visits natural environments as well as the abundance of vegetation in their living environments.
The primary outcome of interest will be emotional, social and behavioural development, primarily assessed using the Strengths and Difficulties Questionnaire. It will be assessed at multiple time points and corroborated from parent and teacher-reported sources. Other mental wellbeing/developmental measures will be used as secondary outcomes. The project will also investigate potential intermediate variables such as air pollution, maternal wellbeing, biomarkers of stress and birth outcomes. Access to the natural environment is often distributed
by social class / socio-economic status. Therefore detailed and multiple dimensional indicators will be used to account for confounding.
B3415 - Investigating the role of genetics in the obese-asthma phenotype in children - 21/11/2019
We now know that children who have asthma and are also obese are more likely to require an urgent visit to the doctor for breathing problems than those who are not obese. Obese children are thought to have a different type of asthma, which is more severe and harder to control. This may be because the current treatments we use to manage daily symptoms do not work very well for this type of asthma. There are many theories that could explain why this is happening. One possible reason could be that the childâs genetic makeup may also play a role in the development of obesity as well as influence their response to treatment.
To address this problem, my proposed project aims to investigate how obesity can affect the response to treatment in children with asthma. In the first phase, I will examine whether obese children with asthma are less likely to respond to standard treatments than those who have normal weight using cutting-edge statistical methods. In the second phase, I will investigate whether certain genetic changes influence the childrenâs ability to respond to asthma treatments and if these same changes are also affected by excess weight.
To do this, I will analyze data that has already been collected from a large number of children with asthma in many different countries, including ALSPAC. The data that will be used for this project forms part of an international collaboration in pediatric asthma, called the Pharmacogenomics in Childhood Asthma (PiCA) Consortium. PiCA is the largest pediatric asthma consortium in the world and has all the necessary data to successfully carry out this research.
I expect the results of this project to help doctors and scientists understand why obese children with asthma are suffering with more severe symptoms than others. Identifying the reasons why they are severe will promote the development of new targeted treatments for children with asthma who have excess weight, with the ultimate goal of improving the management and quality of life for these children.
B3413 - The role of the glycocalyx in cardiovascular and pregnancy health - 22/11/2019
The glycocalyx is a gel-like layer covering the inside surface of all blood vessels. It is essential for normal flow and activity of the blood. Laboratory studies suggest damage to the glycocalyx increases risk of heart disease and pregnancy complications such as preeclampsia, gestational hypertension, gestational diabetes, small and large for gestational age and preterm delivery. Glycocalyx could be a valuable target for disease prevention and treatment. We do not have studies in large numbers of humans that use methods which could help us understand the causal effects of the glycocalyx. The clycocalyx can be measured in two ways: (i) measures in stored blood samples of molecules that are inside the glycocalyx but are shed into the blood when it is damaged (e.g. heparin sulphate proteoglycans, hyaluronic acid and syndecan 1 (SND1) and (ii) microscopic measurement of of small blood vessues under the tongue. We want to add both of these types of measurements to ALSPAC to improve our understanding of how the glycogalix could influence health and well being in pregnancy, during childhood and in adulthood.
B3412 - Environmental exposures in pregnancy and early life influencing cognitive and cardio-respiratory development - 24/11/2019
Exposure to air pollution and road transport noise in pregnancy and early life may affect development of heart, lung and cognitive function that have long-term effects into adult life. However, it is unclear how important this is as there are few studies on the impact of very early life exposures to environmental pollution
B3411 - Using genetically informed designs to disentangle depression - 19/11/2019
Genome-wide association studies (GWAS) have been instrumental in highlighting associations between genetic variants and 1000s of traits. A recent GWAS of major depressive disorder (MDD) by the psychiatric genetics consortium (PGC) has recently identified 102 genetic variants associated with the disorder (Howard et al., 2019). In ALSPAC, genetic liability (indexed by polygenic risk scores) are associated with depression and numerous mood disorder phenotypes. However, genetics are only one side of the story and the interplay between genetic liability and environmental risk factors in the onset and maintenance of depression and related mood disorders is still unclear.
The data will be created by AK and will require a collaborator ID and DAA to have the data stored in Edinburgh on the secure server.
B3409 - The effect of early life exposures on body mass index from early childhood to early adulthood - 19/11/2019
Reducing childhood obesity is a major global public health challenge. However, interventions designed at changing individual or family behaviours often do not show an impact. It is important therefore to better understand the causes of childhood obesity. Whilst there is some evidence that factors in pregnancy are associated with obesity, it is unclear whether these are causes. It is also unclear whether different factors affect obesity at different ages.
For example, there is evidence that children whose mothers had gestational diabetes may have a greater risk of childhood obesity. Studies in Europe and South Asia have also reported that this effect may not emerge until later on in childhood. There is also evidence that infants born preterm are about two-fold more likely to be obese later in life than those born at term. However few studies have examined the association between preterm birth and BMI in later childhood.
In terms of socioeconomic factors, lower family socioeconomic position (SEP) has been associated with higher BMI from as early as 9 months. However, there is inconsistent evidence on the extent as to whether which the effect of SEP increases, decreases or remains constant over time. There is also evidence that neighbourhood exposures in the post-natal period (such as exposure to green spaces and area-level deprivation) are also associated with childhood BMI; however to our knowledge the effect of these exposures before birth has not been investigated.
The LifeCycle project is an EU initiative to harmonise key data from a number of EU studies, including ALSPAC. To maintain participant anonymity, we will be using innovative software called DataSHIELD to analyse the data. DataSHIELD allows the remote analysis of summaries of this harmonised data, but prevents the access of individual data.
The LifeCycle project provides a unique opportunity to examine how early life factors might relate to childhood BMI. In this âproof of principleâ study we will use DataSHIELD to carry out remote analyses of LifeCycle cohorts, selecting variables that have evidence for some effect on childhood BMI (maternal and paternal education, area level deprivation, access to greenspace, gestational diabetes and gestational age at birth). We will conduct analysis on BMI at different points throughout childhood to explore how the effect of these factors emerges over childhood.
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.
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.
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.
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.