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.

Click here to export results in Word format.

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

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

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.

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

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

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

B3394 - Onset of menarche and depressive symptoms from adolescence to adulthood - 11/10/2019

B number: 
B3394
Principal applicant name: 
Abigail Fraser | MRC Integrative Epidemiology Unit (UK)
Co-applicants: 
Miss Claire Prince, Dr Carol Joinson, Dr Jon Heron
Title of project: 
Onset of menarche and depressive symptoms from adolescence to adulthood
Proposal summary: 

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.

Impact of research: 
The findings from this research will building on the evidence and understanding of how pubertal timing affects depression in adolescent girls. This could allow the identification of more at-risk groups of depressive symptoms and therefore inform the development of programmes, particularly in schools, to target these at-risk groups and reduce the risk of depression in young girls.
Date proposal received: 
Friday, 11 October, 2019
Date proposal approved: 
Friday, 11 October, 2019
Keywords: 
Epidemiology, Mental health, Statistical methods, Puberty

B3392 - The interplay of maternal and fetal factors in mechanisms of fetal growth birth timing and related adverse outcomes - 18/10/2019

B number: 
B3392
Principal applicant name: 
Rachel Freathy | University of Exeter (UK)
Co-applicants: 
Dr Robin Beaumont
Title of project: 
The interplay of maternal and fetal factors in mechanisms of fetal growth, birth timing and related adverse outcomes
Proposal summary: 

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.

Impact of research: 
High impact publications improving understanding of mechanisms of fetal growth in human pregnancy, leading to the basis for (i) intervention on modifiable risk factors to reduce adverse pregnancy outcomes, and (ii) stratification of women according to risk, for more appropriate management and treatment in pregnancy.
Date proposal received: 
Tuesday, 8 October, 2019
Date proposal approved: 
Thursday, 10 October, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, Statistical methods, Growth

B3393 - G1 Addition of lung function to G1 clinic 30 - 18/10/2019

B number: 
B3393
Principal applicant name: 
James Dodd | Southmead Hospital, University of Bristol, MRC IEU (United Kingdom)
Co-applicants: 
Raquel Granell, Seif Shaheen, Sailesh Kotecha, Nic Timpson, George Davey Smith
Title of project: 
G1 Addition of lung function to G1 clinic @30
Proposal summary: 

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.

Impact of research: 
Who will benefit? Academic: The principal beneficiaries of this research will be academics who are working in the field of lung development during childhood. There will be opportunities for cross-disciplinary collaborations through the EC COST Action: Developmental Origins of Chronic Lung Disease and we are working on collaborations across the life course, for example, with the ECRHS study to investigate comparative influence of genetic and lifestyle factors on lung function. ALSPAC is a member of several large-scale consortia working on genetic underpinnings of lung function, COPD and asthma, which will benefit from the additional data generated by this research. Data will be shared more widely through the existing ALSPAC data management and dissemination policy. Patients and Public: Increased recognition and understanding of the childhood origins of obstructive lung diseases will benefit patients, their representative organisation, practitioners and the general public understanding of health and disease. Policy Makers: Identification of factors in childhood that can influence life course lung development and resulting adult lung function has policy implications for early recognition of high risk populations, healthcare advice and public health policy to control exposure to adverse factors where possible. Industry: Increased emphasis on early life factors with demonstrable long term influences on lung function potentially opens pathways to modification of current treatment strategies and new therapeutic targets. Linkage to a large repository of biological data has the potential to discover biomarkers of disease phenotypes that could be amenable to personalised approaches to treatment. How will they benefit? Scientific advancement: This proposal will generate new knowledge through understanding some of the important early life influences on the development of lung function. It will also provide the scientific community with data that can be applied to other research questions concerning the genetic and environmental influences on lung function acquisition. This will stimulate further research to identify pathophysiological mechanisms underpinning these associations, contributing to UK scientific capital. Increased understanding and awareness: Patients and Practitioners will benefit from recognition that early life factors are important contributors to the development of obstructive lung diseases in adults. Clinicians will have evidence-based knowledge on which to advise patients about risk factors and interventions, including lifestyle changes. Public understanding about early life risk factors for COPD may shift their attitudes to research in this area, benefiting charitable organisations by increasing available research funding. This work is important to in order to identify interventions to reduce the risk of poor lung health, COPD and associated mortality.
Date proposal received: 
Thursday, 10 October, 2019
Date proposal approved: 
Thursday, 10 October, 2019
Keywords: 
Epidemiology, Respiratory - asthma, COPD, lung health and development, Ageing, Development, COPD, Asthma, lung development, lung health

B3390 - Predictors and patterns of self-harm thoughts and behaviours - 11/10/2019

B number: 
B3390
Principal applicant name: 
Becky Mars | UOB (United Kingdom)
Co-applicants: 
Title of project: 
Predictors and patterns of self-harm thoughts and behaviours
Proposal summary: 

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.

Impact of research: 
work steam 1 will considerably enhance knowledge of the epidemiology of self-harm and will facilitate effective targeting of early interventions to those who are most likely to show a chronic course. It will also improve understanding of the role of adolescent experiences in shaping future health. The knowledge gained from workstream 2 will be important in the design and targeting of interventions aimed at improving help seeking and detection rates for self-harm. This workstream will also inform the early identification of young people who are likely to engage in serious self-harm in the future; a group known to be at high risk for suicide.
Date proposal received: 
Monday, 7 October, 2019
Date proposal approved: 
Tuesday, 8 October, 2019
Keywords: 
Epidemiology, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Development, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3389 - An investigation of the environmental effect of parental genotypes on offspring behavioural problems - 08/10/2019

B number: 
B3389
Principal applicant name: 
Hannah Sallis | School of Psychological Science, University of Bristol (United Kingdom)
Co-applicants: 
Prof Marcus Munafo
Title of project: 
An investigation of the environmental effect of parental genotypes on offspring behavioural problems
Proposal summary: 

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.

Impact of research: 
Date proposal received: 
Monday, 7 October, 2019
Date proposal approved: 
Tuesday, 8 October, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Childhood - childcare, childhood adversity, Genetic epidemiology, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Offspring

B3391 - When Sleeping Like a Baby Isnt So Dreamy - 08/10/2019

B number: 
B3391
Principal applicant name: 
Lawrence Katz | Harvard University (USA)
Co-applicants: 
Kirsten Clinton, Natalia Emanuel
Title of project: 
When Sleeping Like a Baby Isn't So Dreamy
Proposal summary: 

Much of the "Motherhood Penalty" that tips women’s wage trajectories lower than men’s trajectories has been attributed to time out of the labor market – 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 baby’s sleep may have lasting consequences on her parents’ 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

Impact of research: 
We hope that this research will help us understand the causes of the motherhood gap and quantify how important leave policy and paternal involvement are for mitigating this gap. Especially in the US, where the authors are based, the importance of leave and paternal involvement are still hotly debated as there is no national paid leave for mothers, let alone fathers.
Date proposal received: 
Monday, 7 October, 2019
Date proposal approved: 
Tuesday, 8 October, 2019
Keywords: 
Social Science, Statistical methods, Sleep, Social science

B3388 - Dietary intake throughout childhood and adolescence with cardiometabolic health in later life - 04/10/2019

B number: 
B3388
Principal applicant name: 
Kaitlin Wade | MRC-IEU, University of Bristol (United Kingdom)
Co-applicants: 
Dr Emma Anderson, Rosie Fraser
Title of project: 
Dietary intake throughout childhood and adolescence with cardiometabolic health in later life
Proposal summary: 

The aim of this study is to assess the association between dietary intake measured throughout childhood and early adolescence and later cardiometabolic health within a large population.

Impact of research: 
It is currently unclear whether there are sensitive periods during early life that whereby diet has impact cardiometabolic health later in life. Additionally, most studies assessing the impact of childhood nutrition on later health are either of cross-sectional or short-term prospective design, most of which focus on a specific period (e.g., infancy) and are usually restricted to one measure of dietary intake. Repeated measure data is necessary to determine whether there are sensitive periods of early life during which dietary intake is particularly strongly related to later cardiometabolic health to identify suitable target ages for dietary intervention. In parallel, the mechanism by which dietary intake is associated with cardiovascular health requires interrogation, in order to develop more focused strategies aimed to prevent later adverse cardiovascular health.
Date proposal received: 
Thursday, 3 October, 2019
Date proposal approved: 
Friday, 4 October, 2019
Keywords: 
Epidemiology, Obesity, cardiovascular health, Statistical methods, Blood pressure, BMI, Cardiovascular, Childhood - childcare, childhood adversity, Statistical methods

B3387 - Early-life determinants of peak muscle function in adulthood - 22/10/2019

B number: 
B3387
Principal applicant name: 
Alex Ireland | Manchester Metropolitan University (UK)
Co-applicants: 
Prof Jon Tobias, Prof Rachel Cooper
Title of project: 
Early-life determinants of peak muscle function in adulthood
Proposal summary: 

Sarcopenia is defined as the age-related loss of muscle mass and function, occurring in 5-13% of individuals at 60 years of age, leading to increases in premature mortality, functional decline, falls and hospitalisations.

Age-related declines in muscle function are three times greater than those which occur in muscle mass, as changes such as motor unit loss lead to reduced muscle quality. Therefore it is crucial to assess muscle function, mass and quality in order to fully understand the determinants and consequences of sarcopenia.

Studies of sarcopenia to date have focused on identifying factors influencing decline, whereas less well known are the factors which determine peak muscle function. A similar concept of ‘peak bone mass’ is well established in the osteoporosis field, through which several key early-life determinants of bone mass have been identified. Strong relationships exist between muscle and bone, and around a third of individuals with sarcopenia also have osteoporosis. As a result, early-life influences on bone mass accrual may also involve effects on muscle function.

This project will examine whether early-life factors found to influence peak bone mass acquisition, also affect the attainment of peak muscle function. Furthermore, we aim to identify novel factors that contribute to peak muscle function. To do this, we propose to invite attendees to the ALSPAC@30 clinic to undergo a mid-calf peripheral quantitative computed tomography (pQCT) scan, from which muscle mass and density will be derived. We will also use jumping mechanography, a quick, highly-repeatable, sensitive method of assessing muscle function.

Impact of research: 
This application will examine whether early life factors found to influence peak bone mass acquisition, particularly those that are modifiable or amenable to intervention, also affect the attainment of peak muscle function. If true, this would suggest that population based strategies to optimise peak bone mass are likely to be equally effective in optimising peak muscle function, reducing the risk of sarcopenia, osteoporosis and osteosarcopenia in later life. Furthermore, we aim to apply bioinformatics resources such as MR-base (an analytical platform for Mendelian randomisation studies developed by University of Bristol (Hemani et al., 2018)) to identify novel factors and mechanisms that contribute to muscle function.
Date proposal received: 
Wednesday, 2 October, 2019
Date proposal approved: 
Thursday, 3 October, 2019
Keywords: 
Developmental biology, Bone disorders - arthritis, osteoporosis, Sarcopenia, GWAS, Medical imaging, Ageing, Bones (and joints), Development, Physical - activity, fitness, function

B3386 - Impact of parenthood on maternal and paternal neurobiology and subsequent child development - 11/10/2019

B number: 
B3386
Principal applicant name: 
Elanor Hinton | University of Bristol (United Kingdom)
Co-applicants: 
Professor Iain D Gilchrist, Nicholas Timpson
Title of project: 
Impact of parenthood on maternal and paternal neurobiology and subsequent child development
Proposal summary: 

Parenthood is one of the most important events in an adult’s life. Yet there is much to learn about how becoming a parent for the first time influences underlying biology. Researchers have begun to study changes in brain structure and function, as well as functioning of the heart, and pattern of fat and muscle in the body. These changes may help to prepare for the transition to parenthood, but also may have positive and negative consequences for future health. This project aims to study these changes in more detail using magnetic resonance imaging (MRI) by studying adults before and after having their first child. ALSPAC (Avon Longitudinal Study of Parents and Children) is a long-term health project that has studied parents and their children since the early 1990s. The ‘Children of the 90s’ are now having their own children; these births represent an unparalleled time limited opportunity to study the health consequences of pregnancy and parenthood. We will use records collected since birth from the Children of the 90s to predict how their bodies might cope with the challenge of parenthood. There is also much to understand about infant development. By collecting MRI data on the brain and body early in lives of the Children of the Children of the 90s, we will gain greater understanding of how the body develops. By comparing the data from parents with their children, this project will provide a unique opportunity to study the influence of parental biology on their child’s development.

Impact of research: 
Novel and important findings will be made possible through this project by further understanding the changes in body composition and the structure and functioning of the brain and heart during the perinatal period. Thus far, this has been understudied in the literature using small sample sizes. This project has the potential for high impact in this field due to the retrospective analyses made possible by the three generational nature of the dataset and existing detailed phenotypic and genetic records on participants therein. Such analyses will allow us to predict who may be at risk of negative outcomes and to give the possibility of early intervention. Beyond the specific hypotheses specified here, the newly acquired imaging data has huge potential for impact in numerous subject areas through prospective analyses. For example, by imaging the G2 babies early in life, precursors of many health and disease outcomes can be elucidated, including obesity and depression.
Date proposal received: 
Tuesday, 1 October, 2019
Date proposal approved: 
Tuesday, 1 October, 2019
Keywords: 
Neuroscience, Mental health, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Medical imaging, Combining medical imaging data with data already collected on the G1 participants, as well as future data collected on G1 and G2 during clinics., BMI, Cardiovascular, Parenting, Psychology - personality, Childhood - childcare, childhood adversity, Equipment - MRI, Fathers, Genetic epidemiology, Mothers - maternal age, menopause, obstetrics, Neurology, Nutrition - breast feeding, diet, Offspring

B3385 - Spatial Analytics to Prevent Population Health Inequalities in Residential Environments The SAPPHIRE study - 10/10/2019

B number: 
B3385
Principal applicant name: 
James Kirkbride | UCL (United Kingdom)
Co-applicants: 
Prof Eirini Flouri, Prof David Osborn, Prof Gianluca Baio, Prof Ed Manley
Title of project: 
Spatial Analytics to Prevent Population Health Inequalities in Residential Environments: The SAPPHIRE study
Proposal summary: 

Adverse built, social and physical environments are associated with worse mental health outcomes which first emerge in adolescence, offering potentially modifiable population-level targets for prevention. While early detection has become the cornerstone of UK and Australian youth mental health provision, which has led to improved downstream clinical and social outcomes for young people, primary prevention remains an elusive goal, resulting in lifelong physical and mental health disparities which affect whole communities. Hitherto, most studies of the environment and mental health have considered selected indicators from a single domain (built, social or physical), making unobserved and residual confounding major obstacles to causal inference and primary prevention. Methods to characterise the way in which the exposome affects mental health and well-being are now required.

We will address this in two phases.

First, by linking large, geocoded epidemiological and clinical data from ALSPAC with a comprehensive set of built, social and physical environmental exposures via the ALSPAC-PEARL/ALGAE linkage, we will identify the pathways through which these factors affect various mental health outcomes. We will also consider how physical health and activity in childhood may mediate the relationship with later mental health, and vice versa. Environmental data will be linked from multimodal sources available in PEARL/ALGAE and via integration of other available environmental data to characterise the built (building quality, indoor air quality, density, land use, overcrowding, transportation links), social (population density, social isolation and cohesion, inequality, deprivation, ethnic diversity, homelessness, crime) and physical (air, light & noise pollution; accessibility to and quality of green or blue spaces, walkability) environment.

Second, we will develop a simulation platform (SAPPHIRE) to evaluate putative intervention strategies in the built environment to prevent selected adverse mental health outcomes and physical health comorbidities. We will develop a simulation approach based on the ALSPAC sample and the wider population of the Bristol region. We will synthesise theoretical and empirical evidence to build this platform via a hybrid Dynamics/Agent-Based Modelling approach, consistent with capturing the interplay between geospatial, household and individual factors which affect mental health. SAPPHIRE will be open-source, so that decision makers can readily adapt, deploy and test prevention strategies in different contexts based on parameter values representing their local circumstances. This has the potential to unlock primary or secondary prevention strategies in the built environment, which would otherwise be prohibitively expensive, time-consuming or impossible to deploy in the wild.

Impact of research: 
We will identify the most plausible, modifiable targets for prevention of mental health disorders associated with the built environment. We will also produce an open-source spatial analytics simulated environment so that decision makers can readily adapt, deploy and test prevention strategies in different contexts based on parameter values representing their local circumstances. This has the potential to unlock primary or secondary prevention strategies in the built environment, which would otherwise be prohibitively expensive, time-consuming or impossible to deploy in the wild.
Date proposal received: 
Monday, 30 September, 2019
Date proposal approved: 
Monday, 30 September, 2019
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Computer simulations/modelling/algorithms, Childhood - childcare, childhood adversity, Cognition - cognitive function, Environment - enviromental exposure, pollution, Physical - activity, fitness, function, Sleep, Social science

Pages