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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B3530 - Health and wellbeing in surviving congenital heart disease patients - 14/05/2020

B number: 
B3530
Principal applicant name: 
Lucia Cocomello | MRC Integrative Epidemiology Unit, University of Bristol
Co-applicants: 
Professor Deborah A Lawlor, Dr Rosie Cornish, Mr Kurt Taylor, Professor Massimo Caputo
Title of project: 
Health and wellbeing in surviving congenital heart disease patients
Proposal summary: 

Patients with congenital heart (CHD) disease now live longer and therefore they are more likely to experience common aging condition.
One of these are cardiovascular disease (CVD) with relative morbidity and mortality.However, whether the established risk factors for CVD in the general population are the same with CHD is unclear.
In addition, there is a substantial evidence that risk for CVD begins in early life and that risk factors (e.g. obesity, high blood pressure, dyslipidaemia)measured in childhood and adolescence track and relate to adult risk, but the prevalence of these in children with CHD and their future risk on CVD is unknown and may differ from the general population.
Another issue for the aging CHD population is regarding their educational achievement. Academic performance represent a main area of interest as this is anticipated to have major impact in their quality of life. It's well recognised that some children with CHD can present neurocognitive impairment when compared to the general population. However, whether this has a significant effect in their overall academic performance remains unclear with discordant results reported.
To our knowledge there are no study that investigate the trajectories of cardiovascular risk factor and neurocognitive development (in term of educational achievement)from early childhood to adulthood life.

Impact of research: 
There will be a better understanding of cardiovascular risk factors prevalence and trajectories, that could emphasize the importance of primary cardiovascular prevention in the CHD population, irrespective of age. In addition, results on educational outcome and trajectories will provide information to counsel patients, their parents and to provide appropriate support.
Date proposal received: 
Wednesday, 6 May, 2020
Date proposal approved: 
Thursday, 7 May, 2020
Keywords: 
Clinical research/clinical practice, Congenital abnormalities, Statistical methods, Cardiovascular

B3532 - The role of neighbourhood conditions in mental health responses to the Covid-19 lockdown - 15/05/2020

B number: 
B3532
Principal applicant name: 
Joanne Newbury | Population Health Sciences (United Kingdom)
Co-applicants: 
Dr Rebecca Pearson, Andy Boyd
Title of project: 
The role of neighbourhood conditions in mental health responses to the Covid-19 lockdown
Proposal summary: 

The Covid-19 lockdown has shone a light on the importance of where we live for our health and wellbeing. Living in the countryside; having a garden; living in a cohesive neighbourhood; being within walking distance of a park: these factors create very different lockdown experiences, even between neighbours living a stone’s throw apart.

Research into neighbourhood factors and mental health is not new. However, lockdown has created a natural experiment in which people’s activities outside the home are largely being confined to their immediate neighbourhoods. Lockdown has thus amplified the potential detrimental – and protective – effects of neighbourhood conditions on our mental health. Investigating this relationship is not simple. It is important to take into consideration potential factors that might confound associations (e.g., prior mental health). It is also important to take into consideration how individual-level factors such as housing type might modify any associations of neighbourhood characteristics with mental health.

The current project will explore the relationship between neighbourhood characteristics during lockdown – including population density, greenspace, deprivation, and social fragmentation – and people’s symptoms of anxiety and depression during and after lockdown. Analyses will control for key confounders of the association. Moderation of associations according to household composition, housing type, garden access, and perceived access to nature will be explored.

Impact of research: 
The findings will be informative for immediate Covid-19 policy and longer-term policy. In terms of Covid-19 policy, public health experts warn that persistent or intermittent lockdown measures may be required until a Covid-19 vaccine is available – which is not anticipated until 2021. Understanding the role of neighbourhood conditions in mental health during lockdown is therefore an urgent priority that could help to tailor lockdown and social distancing guidance to mitigate impacts on mental health for the most vulnerable and disadvantaged. Longer term, the findings will provide valuable new data on neighbourhood conditions and mental health, and this evidence-base will help policymakers to make the economic case for healthier urban design.
Date proposal received: 
Wednesday, 6 May, 2020
Date proposal approved: 
Thursday, 7 May, 2020
Keywords: 
Epidemiology, Mental health, Statistical methods, Social science

B3527 - Serological testing for COVID19 - 26/05/2020

B number: 
B3527
Principal applicant name: 
Alice Halliday | University of Bristol (United Kingdom)
Co-applicants: 
Professor Adam Finn, Professor Kathleen Gillespie, Dr Alistair Williams, Dr Anna Long, Dr Ashley Toye
Title of project: 
Serological testing for COVID19
Proposal summary: 

There is currently a pandemic of a new disease, COVID19, which is caused by a virus called SARS-CoV-2.

Impact of research: 
Reliable serological tests for SARS-CoV-2 infection are urgently needed to allow us to ascertain the true burden of infection and to develop ways to come out of the current lockdown measures in place to control the pandemic. Vaccination programs will take months/years to implement therefore establishing evidence of natural immunity through antibody testing may be the quickest way back to normal. In addition, this work has huge potential for research tools to allow us to better understand the natural history of SARS-CoV-2 infection in different groups of individuals.
Date proposal received: 
Monday, 4 May, 2020
Date proposal approved: 
Tuesday, 5 May, 2020
Keywords: 
Immunology, Infection, Proteomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Immunity

B3524 - The association between different modes of delivery for childbirth and sexual health a studying using ALSPAC data - 04/05/2020

B number: 
B3524
Principal applicant name: 
Harriet Forbes | Bristol University (UK)
Co-applicants: 
Dr Abigail Fraser, Florence Martin
Title of project: 
The association between different modes of delivery for childbirth and sexual health: a studying using ALSPAC data
Proposal summary: 

Sexual health can impact upon a person’s quality of life. Being pregnant and having a child can affect a woman’s body and mind in a way that may affect their sexual health. We know that when couples have babies, their sexual activity is likely be low in the first few months after the birth. Yet what we don't know is if the mode of delivery (in other words having a vaginal or a ceasrean delivery) affects female sexual health, particularly in the medium to long-term.

Impact of research: 
With some women’s motivation for elective cesarean a perception that their sexual health will be better maintained, and elective cesarean now becoming available on maternal request, better data in this area may help to disprove the link between delivery mode and sexual function, and thereby help curb the rise of cesarean within certain women.
Date proposal received: 
Thursday, 30 April, 2020
Date proposal approved: 
Monday, 4 May, 2020
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes

B3525 - Young adults gambling behaviour in lockdown - 12/05/2020

B number: 
B3525
Principal applicant name: 
Alan Emond | University of Bristol (United Kingdom)
Co-applicants: 
Dr Linda Hollen, Prof Agnes Nairn , Prof Sharon Collard
Title of project: 
Young adults’ gambling behaviour in lockdown
Proposal summary: 

The ALSPAC Gambling study is an ongoing investigation of gambling behaviour in young people, and the antecedents and consequences of problem gambling. The young participants in ALSPAC have previously completed gambling questionnaires and the Problem Gambling Severity Index, at 17, 20- and 24-years.
This proposal will survey the ALSPAC cohort again during the COVID 19 lockdown. This is an excellent opportunity to investigate in real time the effects of COVID-19 mitigation on gambling activities at home by young adults, and to compare individual’s behaviour with what was previously reported at 24 years.

Impact of research: 
These will be unique data, collected during 'real time' of the COVID 19 mitigation, from a well characterized cohort which has answered identical questions previously. The project will provide an insight into the behaviour of young adults during the lockdown.
Date proposal received: 
Friday, 1 May, 2020
Date proposal approved: 
Monday, 4 May, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, gambling, addiction

B3526 - Linking research and routine data to explore childhood asthma eczema and allergic rhinitis in the Born in Bradford birth cohort - 13/05/2020

B number: 
B3526
Principal applicant name: 
Lucy Pembrey | London School of Hygiene and Tropical Medicine (UK)
Co-applicants: 
Dr Gillian Santorelli, Prof John Wright, Prof Neil Pearce, Prof Sinead Langan, Ms Amy Mulick, Dr Raquel Granell
Title of project: 
Linking research and routine data to explore childhood asthma, eczema and allergic rhinitis in the Born in Bradford birth cohort
Proposal summary: 

Asthma, eczema and hay fever and are common diseases in childhood and responsible for a significant burden on families and health services. Atopic eczema, hay fever (allergic rhinitis) and atopic asthma often co-exist. Early diagnosis and appropriate management can reduce progression and severity of these diseases.
The Born in Bradford (BiB) birth cohort includes over 13,500 children born between 2007 and 2011, with around half born to women of Pakistani ethnicity. Linked primary care and hospital admission data are available for 97% of BiB children. Two sub-studies within BiB, the Allergy and Infection Study (ALL IN, n=2559) and Mechanisms of the Development of ALLergy (MeDALL, n=1814), have collected detailed parental questionnaire data at age 1 and 2 years (ALL IN) and at 4 years (MeDALL). The current data collection phase for the whole BiB cohort, Growing Up, at ages 7-11 years is ongoing and also includes questions on these outcomes.
The BiB data provide an opportunity to investigate trajectories of allergic disease and asthma through childhood, by ethnic group. The linked primary care and hospital electronic health records (EHR) will contribute a wealth of data which can be analysed with machine learning methods. There is uncertainty over the validity of routine data but the extensive BiB questionnaire data at different ages provide a rare opportunity to test this.
The aims of this proposed study are:
1) to link research and routine data to explore early life and childhood longitudinal trajectories and describe clinical phenotypes of asthma, eczema and hay fever;
2) to investigate ethnic inequalities in access to care and presentation of these diseases
3) to investigate early life risk factors for these diseases
Questionnaire data are available from the BiB ALL IN sub-study at age 1 year, including questions on pets, family history of asthma/eczema/hay fever, housing conditions (damp, heating, flooring, bedding etc.), and at 2 years (as for age 1 plus eczema, hay fever, food allergy). Detailed data relevant to asthma, eczema and hay fever are available for the MeDALL sub-study participants at 4 years, including skin prick testing for 2269.
BiB receive regular extracts of primary care EHR data on diagnoses and prescriptions for BiB children, which will be linked to the BiB maternal baseline questionnaire data, including socio-demographic and household characteristics. Linked hospital admissions data are available from the Bradford Royal Infirmary. We will also compare EHR data and questionnaire data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
Latent class analysis or other cluster methods, such as k-means clustering, will be used to identify clinical phenotypes of asthma, eczema and hay fever. Longitudinal extensions of these cluster methods will be used to describe trajectories over age.
This study will provide important data on the validity of routine primary care EHR for asthma and allergic diseases, which is relevant as EHR are increasingly used for research studies. The comparison of questionnaire and EHR data will indicate whether there are ethnic differences in access to primary care for these diseases. Identification of clinical phenotypes of asthma, eczema and hay fever will inform appropriate treatment and management and the identification of factors associated with disease progression or severity could indicate potential prevention strategies.

Impact of research: 
This study will provide important data on the validity of routine primary care EHR for asthma and allergic diseases, which is relevant as EHR are increasingly used for research studies. The comparison of questionnaire and EHR data will indicate whether there are ethnic differences in access to primary care for these diseases. Identification of clinical phenotypes of asthma, eczema and hay fever will inform appropriate treatment and management and the identification of factors associated with disease progression or severity could indicate potential prevention strategies.
Date proposal received: 
Sunday, 3 May, 2020
Date proposal approved: 
Monday, 4 May, 2020
Keywords: 
Epidemiology, Allergy, Computer simulations/modelling/algorithms, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3522 - The Healthier Together Population Data Platform - 01/05/2020

B number: 
B3522
Principal applicant name: 
Rachel Denholm | University of Bristol (UM)
Co-applicants: 
Prof. John Macleod, Dr Philip Harfield, Andrew Boyd, Prof. Nicholas Timpson
Title of project: 
The Healthier Together Population Data Platform
Proposal summary: 

Health and care services are increasingly planned and provided using patient data shared securely across multiple health-care settings. However, we know that people’s health is influenced by a wide range of things, including social, cultural, and economic factors. Unfortunately, we don’t currently have data resources that link information about these things to improve service planning, individual care and research.
Our project will fund the information technology and people to bring together information from multiple sources, including, local councils and other services such as the police, as well as the detailed data collected as part of research studies. We will do this using secure technologies and protecting patients’ confidentiality.
By combining and analysing data, we will be able to work with public services to help identify people at higher risk of a condition or disease, and deliver better, more joined up care that is both more effective and offers better value.

Impact of research: 
This application is centred on an existing partnership across NHS organisations, local government, and academia, brought together through the BNSSG Population Health Management (PHM) Steering group to support “Healthier Together” the regional ICS that will succeed the BNSSG Sustainability and Transformation Partnership (STP) over the next two years. As emphasised in the NHS Long-term Plan, the viability and value of an ICS will depend on the availability of a readily analysable person level view of the population and its interactions with the health and care system(5). The BNSSG Systemwide dataset was established for this purpose. The proposed data platform would extend available BNSSG Systemwide dataset linkages beyond the health care system, to include a view of wider determinants of health, such as social care and criminal justice, as well as research data, broadening the application of the resource. Such an integrated data resource would support: a) mapping of patients’ pathways across multiple services b) evaluation and improvement of service delivery across multiple organisations c) understanding of the efficiencies and effectiveness of a whole care system d) understanding public need across the whole system e) the effective rapid response to emerging threats f) understanding wider influences on well-being The opportunities provided with this linkage, and the availability of retrospective and prospective data, have huge potential to inform the effective system response to public health emergencies, such as the COVID-19 pandemic.
Date proposal received: 
Tuesday, 28 April, 2020
Date proposal approved: 
Friday, 1 May, 2020
Keywords: 
Health Services Research/Health Systems Research

B3523 - Fine-mapping of vascular reactivity loci using human artery multi-omics analyses - 01/05/2020

B number: 
B3523
Principal applicant name: 
Clint Miller | University of Virginia (USA)
Co-applicants: 
Title of project: 
Fine-mapping of vascular reactivity loci using human artery multi-omics analyses
Proposal summary: 

Vascular diseases such as hypertension, migraine, and atherosclerosis (hardening of arteries) involve changes in vascular cell function with reduced ability to contract and relax in response to different stresses. This results in chronic alterations in artery blood flow and maladaptive structural changes to the vascular wall leading to injury, tissue damage, and increased risk for life-threatening diseases such as stroke and heart attacks. Given that naturally occurring genetic variation contributes to changes in vascular function along with environmental risk from early life stages, it is now critical to evaluate the effects of these genetic associations at this stage using more systematic approaches. We plan to integrate these vascular phenotype data with high resolution molecular data to better understand how these genetic risk factors impact vascular disease risk at an early age.

Impact of research: 
The results of these analyses will lead to high impact publications and valuable summary datasets to enable the development of novel diagnostic, prognostic and therapeutic strategies to mitigate a range of debilitating vascular diseases.
Date proposal received: 
Tuesday, 28 April, 2020
Date proposal approved: 
Friday, 1 May, 2020
Keywords: 
Genetics, Endothelial dysfunction/artery stiffness (subclinical vascular disease) , Computer simulations/modelling/algorithms, DNA sequencing, Gene mapping, GWAS, Genetic epidemiology, Genetics, Genomics

B3518 - Using a machine learning approach to develop and validate a prediction model for the onset of hypomania - 12/05/2020

B number: 
B3518
Principal applicant name: 
Steven Marwaha | University of Birmingham
Co-applicants: 
Dr Pavan Mallikarjun, Dr Sam Leighton, Miss Danielle Hett, Professor Daniel Smith, Mr Joey Ward
Title of project: 
Using a machine learning approach to develop and validate a prediction model for the onset of hypomania
Proposal summary: 

Bipolar disorder (BD) is a debilitating mental health condition, characterised by severe shifts in mood, that can range from disabling highs (i.e., mania/hypomania) to extreme lows (i.e., depression). Approximately 1% of the population are affected by bipolar (Pini et al., 2005), with most people experiencing the onset of mood symptoms prior to their 20s (Geoffroy et al., 2013). Despite this, little is known about the predictors to bipolar disorder and hypomania symptoms, particularly among young people. Intervening early in the development of bipolar is a top clinical priority, and one that may have the potential to limit its functional and symptomatic impact on those affected. Thus, predicting the onset of bipolar/hypomania prior to its onset, may help clinicians/researchers to develop novel, tailored preventative strategies and interventions for young people.

Impact of research: 
These results will have direct clinical implications for young people who wish to know their risk of developing hypomania, a strong signal of bipolar disorder. Currently, due to the overlap in symptoms, people presenting with bipolar symptoms are often being managed within early intervention services developed for the treatment of psychosis. This could be preventing young people presenting with bipolar symptoms from receiving adequate diagnosis and appropriate treatments early on in their care. Indeed, research suggests that, compared to out-patient treatment, early intervention may be a more clinically and cost-effective tool in managing bipolar. Thus, developing a prediction model for the onset of bipolar, novel preventative/ early intervention programmes— that are tailored to young people specifically—can be developed. This research remains a key clinical priority and will ultimately help towards reducing the psychological suffering of those with bipolar disorder. A prediction model could also enable clinicians to avoid potentially harmful treatments for people at heightened risk of bipolar, such as antidepressants which are known to trigger hypomania in people who are vulnerable to the condition.
Date proposal received: 
Monday, 27 April, 2020
Date proposal approved: 
Friday, 1 May, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3521 - HDR-UK South West Better Care Partnership - 01/05/2020

B number: 
B3521
Principal applicant name: 
Jonathan Sterne | University of Bristol
Co-applicants: 
Prof John Macleod, Dr Rachel Denholm
Title of project: 
HDR-UK South West Better Care Partnership
Proposal summary: 

Better Care South-West Partnership is a collaboration of NHS commissioners, primary, secondary, community and mental health care providers, local authorities, and academia. They look to address real-world health problems using the Bristol, North Somerset and South Gloucestershire (BNSSG) Systemwide health and social care dataset and have an ambition to use individual-level, linked routine care and administrative data to deliver a learning, Integrated Care System for the local population.
The Partnership represents a step change in using advanced analytics to deliver Better Care Loops across a care system and benefit patients and partner organisations. Its results will be scalable across the region and nationally.
Research Projects
· P-NEWS: personalised early warning scores for preventing unplanned critical care admission
· Precision antimicrobial prescribing: safeguarding patient outcomes and preserving future efficacy
· Using operation research methods to improve flow between acute and social care: modelling the responsiveness of system-level expenditure to changes in social care capacity
· Improving hospital efficiency by forecasting demand for hospital beds
· Underpinning infrastructure to the BNSSG Systemwide dataset

Impact of research: 
Date proposal received: 
Tuesday, 28 April, 2020
Date proposal approved: 
Friday, 1 May, 2020
Keywords: 
Health Services Research/Health Systems Research

B3519 - The impact of COVID-19 Lockdown on family interactions and infant behaviours - 30/04/2020

B number: 
B3519
Principal applicant name: 
Rebecca Pearson | Dr (United Kingdom)
Co-applicants: 
Dr Andy Skinner , Professor Paul Moran , Dr Helen Bould , Dr Iryna Culpin
Title of project: 
The impact of COVID-19 Lockdown on family interactions and infant behaviours
Proposal summary: 

The impact of the public health measures adopted to control the COVID-19 pandemic on young infants and family interactions is unknown. New information is vital to inform future policies and recovery for families and aid infant development. Infants may show more unsettled and
restless behaviours even if they are not aware of the situation, however, they may also show positive behaviours benefiting from more parental attention if parents are home. Understanding of both is important to manage further transitions in an ever changing home environment. Furthermore , young children will have been separated from wider family and friends. Online chats may provide a helpful substitute to retain attachments, but how young infants respond to such interactions is unknown . Using our existing methods to code indepeth parent and infant verbal and non-verbal behaviours we can compare parent and infant behaviours in interactions at this time to already collected and coded interactions of ALSPAC-G2 families pre-pandemic. We can also compare infant behaviours towards parents in the same room and a mimicked online interaction (where the one parent joins a chat from another room).

Impact of research: 
A secure adaptation of our current methods would a) allow us to continue to collect these valuable data and b) support the development of a platform for the collection of high-resolution data on family mental health and family interactions at this time of national crisis. The resource being requested would allow us to refine this process with professional experts in product design with whom we already had already begun to forge a successful partnership before the pandemic. The remote solution is also of benefit to our partner projects using the cameras in Africa, Chile and Brazil. Impact: Identifying key sources of changes in risk and resilient behaviours can inform strategies to support families and guide policies for future traumas, including the possibility of a second COVID-19 peak.
Date proposal received: 
Tuesday, 28 April, 2020
Date proposal approved: 
Thursday, 30 April, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition

B3517 - Longitudinal prevalence of covid-19 symptoms in the ALSPAC cohorts - 28/04/2020

B number: 
B3517
Principal applicant name: 
Nic Timpson | ALSPAC / University of Bristol
Co-applicants: 
Dr. Kate Northstone, Dr. Simon Haworth
Title of project: 
Longitudinal prevalence of covid-19 symptoms in the ALSPAC cohorts
Proposal summary: 

Infection by the sars-cov-2 virus (coronavirus) causes a range of flu-like symptoms which can be mild or serious. To date, testing for coronavirus in the Bristol area has focussed on people with severe symptoms. This means that existing test results do not give a full picture of how many people in the Bristol area have already had coronavirus infection.

Rather than using tests, it may be possible to track the spread of coronavirus over time by looking at how many people are experiencing flu-like symptoms. This analysis plans to divide flu-like symptoms into two groups (those which are specific to coronavirus and those which are common in many types of cold or flu) and compare how the rate of these has changed between October 2019 and June 2020. This may give more information about the posible true rate of mild infection in the Bristol area, as well as how the number of people with coronavirus is changing over time.

Impact of research: 
This research should help characterize; a) the approximate proportion of people living in the Bristol area who have reported symptoms of covid-19 and b) the timing (emergence and peak) of these symptoms
Date proposal received: 
Monday, 27 April, 2020
Date proposal approved: 
Tuesday, 28 April, 2020
Keywords: 
Epidemiology, Infection, Statistical methods, Immunity

B3520 - Host genetic effects on covid-19 susceptibility and outcomes - 01/05/2020

B number: 
B3520
Principal applicant name: 
Nic Timpson | ALSPAC / University of Bristol
Co-applicants: 
Dr. Gibran Hemani, Dr. Simon Haworth, Dr. Tom Dudding, Dr. Alex Kwong, Dr. Samuel Neaves, Dr. Kerry Pettigrew
Title of project: 
Host genetic effects on covid-19 susceptibility and outcomes
Proposal summary: 

It is not clear why some people who are exposed to sars-cov-2 (the coronavirus) only develop mild symptoms while others go on to have life-threatening infections. Age and pre-existing medical problems are important, but it is likely that genetic factors also explain why some people are more susceptible to infection. One way to identify the most relevant genetic factors is to screen millions of points across the whole human genome and see which markers are more or less common in people with infection.

This type of analysis (called a genome-wide association study) needs very large studies to generate reliable results, and it is common to run the anlaysis in multiple different studies and then combine results. A global consortium has recently been set up to co-ordinate analysis of host genetic factors and coronavirus. This proposal plans to run genome-wide analysis in ALSPAC and share the results of this anlaysis which can then be combined with other studies globally. To do this it will be necessary to re-impute (re-process) the existing ALSPAC genetic data into an updated format so the results of analysis matches other studies.

Impact of research: 
Results from genetic association anlaysis may help improve understanding of the interplay between host factors and virus which lead to infection or immunity, and lead to mild or severe symptoms during infection. This information may help inform a range of future anlaysis ranging from vaccine development to drug development for patients with severe infection.
Date proposal received: 
Tuesday, 28 April, 2020
Date proposal approved: 
Tuesday, 28 April, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Infection, GWAS, Genetic epidemiology, Genome wide association study

B3515 - Non-invasive Characterisation Diagnosis Prognosis of COVID-19 Respiratory Infection - 27/04/2020

B number: 
B3515
Principal applicant name: 
Dek Woolfson | University of Bristol (UK)
Co-applicants: 
Adam Finn, Dr Catherine Hyams, Professor Stephen Harper
Title of project: 
Non-invasive Characterisation (Diagnosis & Prognosis) of COVID-19 Respiratory Infection
Proposal summary: 
Impact of research: 
COVID-19 diagnostic testing
Date proposal received: 
Wednesday, 22 April, 2020
Date proposal approved: 
Monday, 27 April, 2020
Keywords: 
Immunology, Infection, COVID-19 testing Serological testing Infection Pandemic epidemiology, Biological samples -e.g. blood, cell lines, saliva, etc.

B3514 - Quantifying social contact patterns during the COVID-19 epidemic - 24/04/2020

B number: 
B3514
Principal applicant name: 
Ellen Brooks-Pollock | University of Bristol
Co-applicants: 
Dr Leon Danon, Dr Hannah Christensen, Dr Amy Thomas
Title of project: 
Quantifying social contact patterns during the COVID-19 epidemic
Proposal summary: 

Quantifying social contacts is essential for understanding how a disease will spread in a population. We have measured contact patterns using surveys that have formed the basis of predictive modelling presented at the UK Government Modelling advisory group on COVID-19. Here, we will measure social contact patterns during this unprecedented time of social distancing in the UK and compare to other studies and settings.

Impact of research: 
This work will contribute to predictive COVID-19 modelling in the UK
Date proposal received: 
Tuesday, 21 April, 2020
Date proposal approved: 
Friday, 24 April, 2020
Keywords: 
Epidemiology, COVID19, Mathematical modelling, Reproduction Number, COVID19, mathematical modelling, social contact patterns

B3516 - Exploring the associations between paternal postnatal depression aspects of involvement and parenting and child development - 24/04/2020

B number: 
B3516
Principal applicant name: 
Iryna Culpin | Centre for Academic Mental Health, Population Health Sciences, University of Bristol (United Kingdom)
Co-applicants: 
Xingyu Wang, Dr Jonathan Evans , Dr David Kessler
Title of project: 
Exploring the associations between paternal postnatal depression, aspects of involvement and parenting and child development
Proposal summary: 

There is strong epidemiological evidence to suggest that paternal postnatal depression (PPD) is associated with adverse offspring developmental outcomes in early childhood. However, few large prospective longitudinal studies have examined whether these adverse outcomes persist into later childhood (7 years of age). Furthermore, the offspring outcomes are heterogenous and effect sizes are small to moderate. Thus, it is important to elucidate putative mechanisms, i.e. mediating factors, that underly associations between PPD and offspring adverse developmental outcomes. Such insights are crucial to highlight those at greater risk and develop targeted interventions to reduce adverse outcomes in offspring of depressed fathers. A substantial body of evidence suggests that an important potential mediator is the quality of parenting. Specifically, evidence suggests that PPD disrupts paternal levels of involvement with the offspring and quality of parenting (e.g., bonding, enjoyment, confidence), which, in turn, is associated with adverse offspring outcomes, including emotional and behavioural problems. However, few population-based studies have examined potential explanatory role of fathers’ involvement and parenting in the association between PPD and offspring development using longitudinal mediation models.

Impact of research: 
The role of fathers continues to be overlooked in developmental research, thus, the impact of these findings is likely to be high across several disciplines, including public health, epidemiology and sociology. Although the link between PPD and adverse child development is now well-established, the understanding of mechanisms that underly this association is still lacking. Longitudinal population-based study examining such mechanism is likely to impactful.
Date proposal received: 
Thursday, 23 April, 2020
Date proposal approved: 
Friday, 24 April, 2020
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Parenting

B3512 - What are the dietary lifestyle and socio-demographic predictors of metabolically healthy obesity in adolescence - 21/04/2020

B number: 
B3512
Principal applicant name: 
Genevieve Buckland | Centre for Academic Child Health (United Kingdom)
Co-applicants: 
Dr. Caroline Taylor, Sophie Edwards, Louise Jones
Title of project: 
What are the dietary, lifestyle and socio-demographic predictors of metabolically healthy obesity in adolescence?
Proposal summary: 

The on-going childhood obesity epidemic is accompanied by dramatic increases in childhood metabolic disorders, such as paediatric type 2 diabetes and a cluster of metabolic complications. However, children with obesity are not all equally prone to developing these metabolic disorders; research has shown that there is a subset of obese children who have a more ‘favourable’ health profile, including good insulin sensitivity and normal blood pressure, glucose regulation and blood lipid levels. This has been termed metabolically healthy obesity (MHO), which contrasts with metabolically unhealthy obesity (MUO), where excess body fat is accompanied by metabolic disorders. Since most of the research to date on MHO and MUO has focused on adults, the specific determinants of MHO and MUO in paediatric groups are still not clearly understood.

The concept of metabolically unhealthy and metabolically healthy profiles can also be applied to individuals of ‘normal’ weight, since normal-weight individuals can also have the metabolic and/or inflammatory abnormalities commonly observed in obese people. This group has been termed normal-weight metabolically unhealthy (NWMU). NWMU adults are also at increased risk of cardiometabolic diseases, however, little is known about the health profile and predictive characteristics of NWMU in children.

The relatively high proportion of metabolically healthy individuals in the obese (ranging from 4-60%) and metabolically unhealthy individuals in the lean population suggests that besides from total calories, diet quality could be an important influencing factor on metabolic health. However, few studies have looked at how dietary patterns in children might influence the sub-groups of obesity. Therefore, this study aims to identify which dietary patterns, lifestyle behaviours and socio-demographic factors in children are related to MHO and MUO, as well as NWMU in adolescents. Gaining a clearer understanding of the health profile, characteristics and potential determinants of MHO and MUO in paediatric groups could be valuable in developing more efficient and targeted treatment approaches for these groups of children with obesity.

Impact of research: 
Childhood obesity is associated with increased risk of cardiometabolic disease, type II diabetes, metabolic syndrome and premature mortality. Defining the sub-group of overweight/obese children who remain metabolically healthy (and lean children who are metabolically unhealthy) is important as it can aid in understanding which factors protect against the clustering of metabolic alternations in these sub-groups. Specifically, this study should improve our understanding of the health profile, socio-demographic characteristics and dietary patterns that are associated with metabolic health status in overweight/obese and lean children. This will add to the information available when updating public health guidelines and when developing more efficient personalised approaches for interventions and treatment of obese adolescents based on metabolic health status.
Date proposal received: 
Monday, 20 April, 2020
Date proposal approved: 
Tuesday, 21 April, 2020
Keywords: 
Epidemiology, Obesity, Prospective association analysis, BMI

B3513 - Record Linkage to support Covid-19 Research in ALSPAC Immediate Covid-19 research objectives - 24/04/2020

B number: 
B3513
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
Prof. John Macleod, Prof. Nic Timpson, Dr Catherine Hyams, Dr Ashley Toye
Title of project: 
Record Linkage to support Covid-19 Research in ALSPAC & Immediate Covid-19 research objectives
Proposal summary: 

ALSPAC is well-placed to contribute to the national/international Covid-19 research effort given it has an extensive archive of data about participants health and wellbeing and circumstances prior to the Covid-19 outbreak and is now collecting data specifically related to Covid-19. These data can be used with our biobank and genetic data.

This project seeks to enhance these data with NHS and other Covid-19 records. These will bring timely information about symptoms, help-seeking and care and disease outcomes. It will allow ALSPAC to look at Covid-19 specific health (i.e. the health of those with the virus) and wider general physical and mental health (which may be impacted by stretched NHS resources during the outbreak, or due to the 'lock-down' and social distancing).

This data will sit alongside the other health records ALSPAC have collected. The same security mechanisms will be used to keep the data confidential, and ALSPAC will not extract records from participants who have objected to this use of their data.

The records will be sourced from:

1) A new NHS national (English) repository of Covid-19 data (GP records, Hospital Records, Pharmacy data, NHS 111 call records, Ambulance Records, Mortality Records, Covid-19 testing records).
2) Respiratory care records from databases at NHS University Hospital Bristol Trust and NHS North Bristol Trust hospitals.
3) Records from the 'Zoe' symptom tracker app.

ALSPAC will immediately use the data to help understand more about the factors that influence the susceptibility and severity of Covid-19. We will also examine whether Blood Group and the FUT2 gene (and other genes) are associated with Covid-19 susceptibility.

Impact of research: 
To contribute Covid-19 records to ALSPAC's research program. To help facilitate research insights to the NHS & government policy makers.
Date proposal received: 
Tuesday, 21 April, 2020
Date proposal approved: 
Tuesday, 21 April, 2020
Keywords: 
Epidemiology, Infection, Record lInkage, Linkage

B3511 - Environment DNA methylation and risk of childhood acute lymphoblastic leukaemia a novel two-sample MR study - 24/04/2020

B number: 
B3511
Principal applicant name: 
Aayah Nounu | The University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
Environment, DNA methylation and risk of childhood acute lymphoblastic leukaemia: a novel two-sample MR study
Proposal summary: 

Acute lymphoblastic leukaemia (ALL) is the most common cancer in children. Whilst a range of genetic abnormalities have been identified as crucial in disease initiation, these abnormalities alone are not sufficient for transformation. Maternal exposures during pregnancy such as smoking, or folate intake have the potential to impact on offspring DNA methylation. This epigenetic mark has also been shown to be altered in ALL. We have previously identified 5 CpG sites that have altered DNA methylation due to maternal smoking and folate intake and we aim to identify whether changes to DNA methylation at these sites affects risk of ALL.

Impact of research: 
The exact reasons and risk factors associated with childhood ALL is still not well understood. Through this analysis, we might be able to understand how maternal exposures during pregnancy may impact risk of ALL in offspring. This has the potential to be used in policy making, especially when advising mothers on smoking and folate intake during pregnancy.
Date proposal received: 
Monday, 20 April, 2020
Date proposal approved: 
Tuesday, 21 April, 2020
Keywords: 
Epidemiology, Cancer, Statistical methods, Mendelian randomisation

B3508 - A robust micro-assay to determine the prevalence of COVID-19 antibodies in the general population using capillary sample collect - 24/04/2020

B number: 
B3508
Principal applicant name: 
Kathleen Gillespie | University of Bristol (UK)
Co-applicants: 
Title of project: 
A robust micro-assay to determine the prevalence of COVID-19 antibodies in the general population using capillary sample collect
Proposal summary: 

The Diabetes and Metabolism Unit at Southmead has a long history of measuring antibodies. Over the last three years we have focused on a particular type of assay which works on very small samples of blood. We have also good systems for sending small tubes by post which allow people to take a small blood sample from their finger and post it safely back to the laboratory for antibody testing. Since the recent COVID-19 pandemic we do not know how many people have been infected by the virus and this is a very important question. We have been working closely with a research group in Milan who have developed a test to work out who has been infected with Covid-19 because they have antibodies to the virus. Initial tests suggest that this assay works well on very small blood samples. We are now setting up this assay in Bristol and are requesting to access some samples from ALSPAC for
1. a University of Bristol study to test different assay platforms using the same samples
2. to prospectively and safely collect low volume samples by post and use the assay to estimate the infection rate in the general population and link this to questionnaire based data regarding symptoms.
This study should allow us to work out quickly and reliably how many people in the ALSPAC population have had COVID-19.

Impact of research: 
We thick it could be very important as our assay allows samples to be safely collected and tested under lockdown conditions.
Date proposal received: 
Friday, 17 April, 2020
Date proposal approved: 
Monday, 20 April, 2020
Keywords: 
Immunology, Infection, Immunoassay , Immunity

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