Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B3416 - Investigating a DNA methylation signature of e-cigarette use - 29/11/2019

B number: 
B3416
Principal applicant name: 
Rebecca Richmond | University of Bristol (UK)
Co-applicants: 
Matthew Suderman, Paul Yousefi, Marcus Munafo, Caroline Relton, Suzanne Gage
Title of project: 
Investigating a DNA methylation signature of e-cigarette use
Proposal summary: 

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 (“vapers”) 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.

Impact of research: 
These results will be of direct relevance to health professionals and policy makers. If we find vaper methylation patterns similar to those of smokers, this might indicate that long-term health risk is similar. If, conversely, e-cigarette methylation patterns are more akin to patterns seen in non-smokers, this might provide evidence that their use as a smoking-cessation device could be encouraged. This information is important to governments and organisations making e-cigarette policy and legislation decisions.
Date proposal received: 
Wednesday, 20 November, 2019
Date proposal approved: 
Thursday, 21 November, 2019
Keywords: 
Epigenetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, epigenome-wide association study, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics

B3414 - The Association between the Natural Environment and Emotional Social and Behavioural Development - 02/12/2019

B number: 
B3414
Principal applicant name: 
Dr Benedict Wheeler | University of Exeter (UK)
Co-applicants: 
Mr Mark Ferguson, Dr Alison Teyhan, Dr Rosie McEachan, Dr Rebecca Lovell , Mr Andy Boyd, Prof John Macleod
Title of project: 
The Association between the Natural Environment and Emotional, Social and Behavioural Development
Proposal summary: 

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.

Impact of research: 
The primary impact of this research will be to develop the evidence base on the connection between natural environments/ Greenspace and childhood development. Many studies in the field have been cross-sectional. Therefore adding a study with highly detailed temporal data will enhance the evidence base, particularly if submitted for publication in a high-quality journal. The variables available within ALSPAC will allow for the development of greenspace exposure metrics beyond what is often used in greenspace and health studies. This will help to understand which metrics (i.e. geospatial or self-reported metrics) are most appropriate; it will enable a greater understanding of what aspect(s) of the natural environment are likely to influence child development. For example, whether active usage or passive exposure is more prominent and at which stages of the life course may be more sensitive. Utilising this data will be impactful for ALSPAC and PEARL and display the increasing potential of linking cohort studies to geospatial data temporally.
Date proposal received: 
Tuesday, 19 November, 2019
Date proposal approved: 
Thursday, 21 November, 2019
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Development, Environment - enviromental exposure, pollution

B3411 - Using genetically informed designs to disentangle depression - 19/11/2019

B number: 
B3411
Principal applicant name: 
Alex kwong | UoB / IEU / Uni of Edinburgh
Co-applicants: 
Dr Mark Adams, Professor Andrew McIntosh
Title of project: 
Using genetically informed designs to disentangle depression
Proposal summary: 

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.

Impact of research: 
elucidate pathways to depression
Date proposal received: 
Friday, 15 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3409 - The effect of early life exposures on body mass index from early childhood to early adulthood - 19/11/2019

B number: 
B3409
Principal applicant name: 
Tim Cadman | IEU, Bristol University
Co-applicants: 
Professor Deborah Lawler, Dr Ahmed Elhakeem, Johan Lerbech Vinther, Serena Fossati, Anne-Marie Nybo Andersen, Kate Northstone
Title of project: 
The effect of early life exposures on body mass index from early childhood to early adulthood
Proposal summary: 

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 ‘proof of principle’ 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.

Impact of research: 
Date proposal received: 
Thursday, 14 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Epidemiology, Obesity, Statistical methods, BMI

B3413 - The role of the glycocalyx in cardiovascular and pregnancy health - 22/11/2019

B number: 
B3413
Principal applicant name: 
Deborah Lawlor | MRC IEU at the University of Bristol (United Kingdom)
Co-applicants: 
Prof Simon Satchell, Dr Victoria Bills, Dr Colin Down, Dr Tom Richardson
Title of project: 
The role of the glycocalyx in cardiovascular and pregnancy health
Proposal summary: 

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.

Impact of research: 
Increased understanding of the role of the glycocalyx on cardiovascular and pregnancy health. Discovery of a potential target for preventing cardiovascular diseases and pregnancy disorders
Date proposal received: 
Tuesday, 19 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, BMI

B3412 - Environmental exposures in pregnancy and early life influencing cognitive and cardio-respiratory development - 24/11/2019

B number: 
B3412
Principal applicant name: 
Anna Hansell | University of Leicester, Centre for Environmental Health and Sustainability (United Kingdom)
Co-applicants: 
Miss Yingxin Chen, Miss Katie Eminson, Professor John Gulliver, Dr Calvin Jephcote
Title of project: 
Environmental exposures in pregnancy and early life influencing cognitive and cardio-respiratory development
Proposal summary: 

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

Impact of research: 
The findings of this project will provide new knowledge to inform UK and European policy, with relevance to design and placement of new housing, schools and roads, and to noise and air pollution abatement schemes. Dissemination will be through our existing links with the Noise and Nuisance Technical and Evidence Team at DEFRA, through candidate attendance at international conferences (International Commission for the Biological Effects of Noise conference in 2020 and the Internoise conference 2021) and publication of peer-reviewed journal papers. It is intended to publish results in high impact journals at the end of the project, which might contribute to policy decision-making and/or future follow-up studies.
Date proposal received: 
Monday, 18 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Epidemiology, Developmental disorders - autism, Cognitive impairment, Diabetes, Hypertension, Learning difficulty, Mental health, Respiratory - asthma, Speech/language problem, CVDs, lung function, Computer simulations/modelling/algorithms, Statistical methods, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, Offspring, Parenting, Psychology - personality, Physical - activity, fitness, function, Social science, Speech and language, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Development, Environment - enviromental exposure, pollution, Growth, Intelligence - memory, Linkage

B3410 - Testing the role of relative age within school year on mental health in children with neurodevelopmental vulnerability - 24/11/2019

B number: 
B3410
Principal applicant name: 
Stephan Collishaw | Cardiff University (UK)
Co-applicants: 
Mr Tom Broughton, Professor Kate Tilling, Dr Kate Langley, Dr Richard Anney
Title of project: 
Testing the role of relative age within school year on mental health in children with neurodevelopmental vulnerability
Proposal summary: 

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.

Impact of research: 
This project will likely be impactful as it aims to be assess whether age at school entry is causally associated with later mental health difficulties in specific at-risk groups. The project will help identify those children who are at highest risk of later mental health problems, and who are therefore a priority for early support and preventative intervention. Furthermore, identifying a group(s) of children who would benefit from delaying school entry has potentially significant individual, family and societal benefits. Currently, guidance in England and Wales indicates that it is possible to delay school entry if there is a ‘compelling reason’. However, decisions on deferred school entry are often left to individual school admission boards, and policy varies between the devolved nations. The project will provide comprehensive evidence on whether children at risk should be rigidly assigned to school entry based on date of birth or given greater flexibility regarding school entry, taking into account developmental maturity. Therefore, the findings of this project would be of significant interest to parents, carers, and teachers of premature children and children with neurodevelopmental disorders, as well as charities that advocate for these groups. The findings will also be of interest to the Welsh Government, UK Government, and local education authorities.
Date proposal received: 
Friday, 15 November, 2019
Date proposal approved: 
Sunday, 17 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Genetic epidemiology, Statistical methods

B3408 - International Cannabis Consortium - GWAMA of quantity/frequency of cannabis use - 14/11/2019

B number: 
B3408
Principal applicant name: 
Lindsey Hines | Population Health Sciences
Co-applicants: 
Dr Robyn Wootton, Dr Hannah Sallis, Professor Marcus Munafo
Title of project: 
International Cannabis Consortium - GWAMA of quantity/frequency of cannabis use
Proposal summary: 

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.

Impact of research: 
The consortium has published several successful GWAS meta-analyses over the years, including lifetime use and age at initiation. This it the first meta-analysis on the frequency of cannabis use. Frequency of use is a key determinant of the harms of cannabis use, and developing the GWAS for this phenotype is critical for understanding the relationship between cannabis and mental health.
Date proposal received: 
Wednesday, 13 November, 2019
Date proposal approved: 
Thursday, 14 November, 2019
Keywords: 
Genetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, GWAS, Genome wide association study

B3407 - Identifying genetic variants predisposing to overeating behaviour - 10/01/2020

B number: 
B3407
Principal applicant name: 
Fotios Drenos | Brunel University London and University College London
Co-applicants: 
Dr Terry Dovey
Title of project: 
Identifying genetic variants predisposing to overeating behaviour
Proposal summary: 

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 individual’s 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.

Impact of research: 
To identify the genetic predisposition of overeating and the markers predicting the behaviour. To use this information to better understand overconsumption and the potential behavioural interventions that can be used to avoid overeating and associated health problems.
Date proposal received: 
Monday, 11 November, 2019
Date proposal approved: 
Tuesday, 12 November, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Diabetes, Eating disorders - anorexia, bulimia, Obesity, Computer simulations/modelling/algorithms, GWAS, Metabolomics, BMI, Cardiovascular, Genetic epidemiology, Genome wide association study, Mendelian randomisation, Metabolic - metabolism, Psychology - personality

B3406 - Acceptability to participants of novel data linkages ethical issues and the practicalities of obtaining consent Evidence from - 21/11/2019

B number: 
B3406
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
Kate Shiells, Oliver Davis, Andy Skinner, Nic Timposn
Title of project: 
Acceptability to participants of novel data linkages, ethical issues, and the practicalities of obtaining consent: Evidence from
Proposal summary: 

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.

Impact of research: 
To inform funders and longitudinal studies about the potential for novel 'Digital Footprint' data sources and to emphasis the ethical and safeguard dimensions to this.
Date proposal received: 
Monday, 11 November, 2019
Date proposal approved: 
Monday, 11 November, 2019
Keywords: 
Statistics/methodology, study methodology, research ethics, data linkage., Qualitative study, Cohort studies - attrition, bias, participant engagement, ethics

B3404 - Analysing the association between inflammation and scoliosis in a population-based birth cohort a proof of concept study - 11/11/2019

B number: 
B3404
Principal applicant name: 
Emma Clark | University of Bristol
Co-applicants: 
Prof Brian Ciruna
Title of project: 
Analysing the association between inflammation and scoliosis in a population-based birth cohort – a proof of concept study
Proposal summary: 

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.

Impact of research: 
Potentially huge: Scoliosis affects 4% of the population and current treatment options are limited to rigid brace-wearing or surgical correction. We have already demonstrated that over-the-counter anti-inflammatory and antioxidant drugs can prevent severe spinal curve progression in animal models of idiopathic scoliosis. If the results of this study link similar pathogenic mechanisms to human disease, this research could have profound impacts on future treatment and prevention strategies for scoliosis.
Date proposal received: 
Friday, 8 November, 2019
Date proposal approved: 
Monday, 11 November, 2019
Keywords: 
Epidemiology, Bone disorders - arthritis, osteoporosis, Statistical methods, Immunity

B3405 - DNA methylation signatures of aggressive behavior - 11/11/2019

B number: 
B3405
Principal applicant name: 
Matthew Suderman | IEU (United Kingdom)
Co-applicants: 
Title of project: 
DNA methylation signatures of aggressive behavior
Proposal summary: 

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.

Impact of research: 
A publication presenting the best biomarkers from peripheral blood DNA methylation to date for aggression. These will be used to better understand the biological correlates of aggression as well as to understand molecular associations with other phenotypes and exposures.
Date proposal received: 
Friday, 8 November, 2019
Date proposal approved: 
Monday, 11 November, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Genomics

B3402 - Quantitative triangulation in aetiological epidemiology - 07/11/2019

B number: 
B3402
Principal applicant name: 
Julian Higgins | University of Bristol (PHS) (UK)
Co-applicants: 
Kate Tilling
Title of project: 
Quantitative triangulation in aetiological epidemiology
Proposal summary: 

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.

Impact of research: 
Primarily generation of novel quantitative framework for epidemiological triangulation.
Date proposal received: 
Tuesday, 5 November, 2019
Date proposal approved: 
Thursday, 7 November, 2019
Keywords: 
Statistics/methodology, We are currently not able to select a disease/condition., Statistical methods

B3403 - Validation of alcohol score as a negative control - 07/11/2019

B number: 
B3403
Principal applicant name: 
Tom Richardson | MRC Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Ms Si Fang, Prof George Davey Smith
Title of project: 
Validation of alcohol score as a negative control
Proposal summary: 

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.

Impact of research: 
A better understanding of how alcohol influences cardiovascular disease risk.
Date proposal received: 
Wednesday, 6 November, 2019
Date proposal approved: 
Thursday, 7 November, 2019
Keywords: 
Epidemiology, Hypertension, GWAS, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3401 - Associations between experience of sexual violence birth experience and perinatal mental health outcomes - 31/10/2019

B number: 
B3401
Principal applicant name: 
Rebekah Shallcross | The University of Leeds
Co-applicants: 
Professor Liz Hughes, Dr Hein Heuvelman
Title of project: 
Associations between experience of sexual violence, birth experience and perinatal mental health outcomes
Proposal summary: 

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.

Impact of research: 
This work will form the basis of one Work Package in a larger body of work submitted for funding to the NIHR around the experience of childhood sexual abuse (CSA), adult sexual assault, its impact on the birth experience, and subsequent perinatal mental health and wellbeing. Currently there are is no large quantitative evidence on the interaction between previous experience of sexual violence, birth experience and perinatal mental health and thus this piece of research will begin to build an evidence based by utilising already collected data on sexual violence, thus reducing burden upon survivors of assault. In doing so we aim to establish the size and nature of the problem. This work will then feed into a larger body of work with the providing services that meet the needs of survivors of sexual abuse and assault.
Date proposal received: 
Thursday, 31 October, 2019
Date proposal approved: 
Thursday, 31 October, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Mothers - maternal age, menopause, obstetrics

B3399 - Integrating longitudinal and cross-national evaluations of increased community alcohol availability and the health and economic - 08/11/2019

B number: 
B3399
Principal applicant name: 
Frank de Vocht | Population Health Sciences, University of Bristol (United Kingdom)
Co-applicants: 
Dr Bosco Rowland, Professor John Toumbourou, Dr Jon Heron, Professor Peter Miller, Dr Michael Livingston, Professor Matt Hickman, Dr Cheryl McQuire, Dr Inês Henriques-Cadeby, Mr Colin Angus, Dr John Holmes
Title of project: 
Integrating longitudinal and cross-national evaluations of increased community alcohol availability and the health and economic
Proposal summary: 

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 participant’s 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.

Impact of research: 
The detrimental and causal impact of alcohol on non-communicable disease is well understood as are the links between alcohol availability, alcohol consumption and alcohol-related harms in adults. It is much less clear how increasing alcohol availability in local, and especially urban, built environments is causally linked to the uptake and frequency of consumption by children and adolescents, and the extent to which this may impact on health and well-being and consumption later in life. Thus, for this project, the academic impact of publishing high-quality, definitive evidence identifying these links is critical to the societal and policy impact of the proposed research. Using cross-national, longitudinal datasets and novel analyses, we will generate the best available evidence on how increasing alcohol outlets in cities is affecting children and adolescents’ alcohol use, their health and futures and the costs to local and national governments of trends in alcohol consumption among young people. The planned analyses will also identify what factors facilitate or impede the regulation of alcohol outlets in the community. From the first year we will interview stakeholders and policy makers (as part of WP6) to identify key questions that guide current licencing policy and ensure that our analyses addresses these issues. We will use qualitative analyses of interview data, observations of the history of licencing objections and analyses of local legalisation and practices to map out the processes by which policy is translated into licencing practice in Bristol and Melbourne. To maximise the impact of the project we are in the process of establishing an Expert Study Advocacy and Advisory Group (SAAG), for which we already have support from Public Health England, Public Health Association of Australia, the Institute of Alcohol Studies and from academia (Letters of Support included), and we aim to include further representation from stakeholders and the general public. The SAAG will be established to help identify how to best facilitate and promote findings. We anticipate that, we will write a series of brief policy and community information sheets targeting policy makers and community leaders. These will outline the main findings and recommendations arising from our research, including recommendations for policy and legislative change. We will also provide a “managing the process” community resource pack. It is easy to find “what-to-do” guidelines if you want to get a new alcohol licence (e.g., https://impos.com.au/blog/alcohol-licence-guide-australia/) and, for example, the VCGLR, sets out clearly how to object to new licences (https://www.vcglr.vic.gov.au/community-services/objecting-liquor-licence-application). However, it is less clear how community representatives can manage extant processes and advocate for policy and practice change. We will provide evidence-based guidelines to managing these processes that link directly to local policy frameworks. In addition, towards the end of the project we will we will run three workshops, one for community leaders in Melbourne and one for legislators in Canberra, while in the UK one workshop will be organised (location to be decided) for policy makers, local councils, NGOs, other stakeholders and the general public. These workshops will allow us to present not only the results of our data analyses but also our recommendations for policy and practice change that are compatible with a harm minimisation approach to the marketing of alcohol products. These workshops will highlight our findings in terms of the health, community and economic impact of current policies. We will present alternative legislative and policy futures and map out their likely health, community and economic consequences, based on our results. We will also identify road maps to harm minimisation policy development.
Date proposal received: 
Tuesday, 29 October, 2019
Date proposal approved: 
Thursday, 31 October, 2019
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Qualitative study, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Social science, Statistical methods

B3400 - Assessment of lung function decline in young adults identifying and characterising early expressions of COPD - 10/12/2019

B number: 
B3400
Principal applicant name: 
Ramesh Jagath Kurukulaaratchy | University of Southampton (United Kingdom)
Co-applicants: 
Professor Hasan Arshad, Professor John Holloway, Professor Graham Roberts
Title of project: 
Assessment of lung function decline in young adults; identifying and characterising early expressions of COPD.
Proposal summary: 

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.

Impact of research: 
This research has potential to significantly enhance understanding of how COPD develops and what might be done to reduce the impact of that disease. Early identification of COPD through the findings of this research could have a significant impact on individual patient management by focusing early interventions including medication and lifestyle changes. That can have significant impact on the burden of COPD at a wider societal level in due course and mitigate the financial and resource burden of that high morbidity disease state in later life. Awareness of what predisposes declining lung function in early adulthood could also lead to meaningful interventions to prevent that process and associated COPD-risk.
Date proposal received: 
Wednesday, 30 October, 2019
Date proposal approved: 
Thursday, 31 October, 2019
Keywords: 
Clinical research/clinical practice, Lung Function Trajectories COPD risk, Lung Function Measurements, lung imaging., Physiological trajectories

B3398 - Predicting Childhood Language Disorder and Ability using Genome-Wide Polygenic Scores - 28/10/2019

B number: 
B3398
Principal applicant name: 
Umar Toseeb | University of York
Co-applicants: 
Dr Dianne Newbury, Dr Kathryn Asbury
Title of project: 
Predicting Childhood Language Disorder and Ability using Genome-Wide Polygenic Scores
Proposal summary: 

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.

Impact of research: 
Currently, it is difficult to identify children with language disorders until aged 4-5 years old because language is unpredictable before then. This is not ideal. We hope that the proposal will be a major step towards genetic screening for risk of language disorders, which may ultimately allow for interventions to be put in place much earlier than is currently possible.
Date proposal received: 
Thursday, 24 October, 2019
Date proposal approved: 
Monday, 28 October, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Speech/language problem, GWAS, Development, Genetics, Genomics, Genome wide association study, Speech and language

B3397 - Religious belief health and disease a family perspective - 06/11/2019

B number: 
B3397
Principal applicant name: 
Jean Golding | University of Bristol
Co-applicants: 
Dr Kate Northstone, Dr Abigail Fraser, Prof Nicholas Timpson, Prof Yoav Ben Shlomo, Dr Carol Joinson, Prof Alan Eamond, Dr Yaz Iles-Caven
Title of project: 
Religious belief, health and disease: a family perspective.
Proposal summary: 

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.

Impact of research: 
Date proposal received: 
Thursday, 24 October, 2019
Date proposal approved: 
Monday, 28 October, 2019
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Blood pressure, BMI, Cardiovascular, Epigenetics

B3395 - Emotional dysregulation self-harm and eating disorders a mechanistic investigation - 17/10/2019

B number: 
B3395
Principal applicant name: 
Helen Bould | University of Bristol (United Kingdom)
Co-applicants: 
Prof Paul Moran, Prof David Gunnell, Dr Becky Mars, Dr Jon Heron, Dr Anne Stewart, Prof Marcus Munafo, Prof Ian Penton-Voak, Dr Andy Skinner, Dr Lucy Biddle, Dr Naomi Warne
Title of project: 
Emotional dysregulation, self-harm and eating disorders: a mechanistic investigation
Proposal summary: 

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

Impact of research: 
1) Scientific advancement and impact upon the research community: The aim of this research is to enhance understanding about the aetiology of eating disorders and self-harm, and particularly how they relate to a common precursor of emotional dysregulation. Given that the personal and economic burden of eating disorders and self-harm is substantial, there is a pressing need for more effective strategies for treatment and prevention. We envisage that the research will assist in the identification of novel treatment targets, as well as potential prognostic markers. 2) Service users and families: Ultimately, we hope that the research will contribute to better prevention and treatment strategies for people who self-harm and also those with eating disorders. In doing so, we hope that it will help to reduce the suffering and accelerate the recovery of people with these common and burdensome mental health conditions. Increasing understanding of the aetiology of these conditions will, we think, also help to reduce the stigma associated with them. 3) Clinical community: Our findings could lead to the identification of early markers of self-harm and eating disorders risk. This would aid the early identification of young people who are at increased risk of self-harm and eating disorders and enable more efficient targeting of resources to those who are most in need, and most likely to benefit from early intervention. In addition, a better understanding of underlying mediators such as bullying, social cognition and emotion recognition will enable the development of successful novel treatment strategies. 4) Development of capacity and capability: The project will support the career development of a talented new PI in the field of eating disorder research (HB), also enabling her to broaden her research experience into the area of self-harm. Our proposal brings together an outstanding multidisciplinary team of academic experts who will be supporting HB throughout the project. Such a partnership is extremely rare, and the infrastructural funding underpinning this partnership will potentially allow our team to develop further competitive proposals tackling the issue of self-harm and eating disorders. In addition, the two researchers employed on the study will develop new skills through the analysis, write-up and presentation of study findings. These skills will be invaluable in terms of their future career development.
Date proposal received: 
Tuesday, 15 October, 2019
Date proposal approved: 
Tuesday, 15 October, 2019
Keywords: 
Clinical research/clinical practice, Eating disorders - anorexia, bulimia, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

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