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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B3540 - Wellcome Longitudinal Population Study LPS COVID-19 Steering Group Secretariat - 17/05/2020

B number: 
B3540
Principal applicant name: 
Nic Timpson | University of Bristol
Co-applicants: 
Professor David Porteous
Title of project: 
Wellcome Longitudinal Population Study (LPS) COVID-19 Steering Group & Secretariat
Proposal summary: 

Seeking financial support to enable a secretariat for a newly formed steering group aimed at most effectively using UK population research resources to address questions relevant to the ongoing COVID-19 pandemic (£120585 over 12 months).

Impact of research: 
The COVID pandemic has already demonstrated that population research resources can be aligned around a common research goal and that a modest infrastructure investment can yield an efficient response which levers value from previous funder investment. This proposal is focused on the bringing together of UK population-based resources through the explicit and real generation, administration and analysis of a multi-study COVID-19 questionnaire. It is purposefully limited to this objective, but will create a model of agile, coordinated responses to emergent questions of high public interest that no one cohort can adequately address. This is beyond the scope of the immediate priority and capacity of the Secretariat, but the box below outlines one obvious extension to the concept.
Date proposal received: 
Friday, 15 May, 2020
Date proposal approved: 
Sunday, 17 May, 2020
Keywords: 
Research management., Infection, RNA, LPS

B3535 - Atopic dermatitis filaggrin null mutations and COVID-119 - 17/05/2020

B number: 
B3535
Principal applicant name: 
Sinead Langan | London School of Hygiene and Tropical Medicine (United Kingdom)
Co-applicants: 
Ms Amy Mulick, Professor Alan Irvine
Title of project: 
Atopic dermatitis, filaggrin null mutations and COVID-119
Proposal summary: 

Atopic Dermatitis (AD, also known as atopic eczema and eczema) is a common disease affecting 20% of children in the UK and other high-income countries. The major genetic risk factor for AD is loss of function mutations in filaggrin, a critical skin barrier protein. There are many theories around the high prevalence of filaggrin mutations in European and Asian populations and of eczema including some proposals that having a leaky skin barrier and an overactive skin immune system might lead to skin immune cells being activated through the skin resulting in protection against pandemics. The COVID-19 pandemic is associated with substantial COVID-related health problems and deaths.

We will use data from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective birth cohort study questionnaires and clinical visits to identify people with evidence of eczema in childhood, and genetic data to identify people with filaggrin null mutations. We are very familiar with these data in ALSPAC and have very recently analysed these data. We will then determine if people in early adulthood (the age of the cohort at the time of pandemic emergence) with evidence of childhood eczema are at reduced risk of reporting symptoms suggestive of COVID-19. The subsequent analysis will involve assessing if those with filaggrin null mutations (with and without eczema) have reduced risk of reporting COVID-19 symptoms. We will stratify by the presence or absence of asthma to see if the risks vary in these subgroups.

Impact of research: 
This study is hypothesis testing. We will test the hypothesis that young people who had eczema in childhood have reduced risk of reporting symptomatic COVID-19 infection during the first weeks of the pandemic, and the hypothesis that having filaggrin null mutations might be protective against symptomatic COVID-19 infection in young people during the first weeks of the pandemic. If we do discover that eczema and filaggrin null mutations are protective, this could have important implications for the wider population in relation to shielding advice but also potential novel therapeutic interventions taking advantage of the skin barrier to prime the immune system. This work will result in high impact papers, conference presentations.
Date proposal received: 
Monday, 11 May, 2020
Date proposal approved: 
Sunday, 17 May, 2020
Keywords: 
Epidemiology, Allergy, Statistical methods, Dermatology

B3539 - Family background and the intergenerational transmission of educational attainment A multi-cohort analysis - 28/05/2020

B number: 
B3539
Principal applicant name: 
Jasmin Wertz | Duke University (USA)
Co-applicants: 
Avshalom Caspi, PhD, Terrie E. Moffitt, PhD, Karen Sudgen, PhD , David Corcoran, PhD, Renate Houts, PhD, Sophie von Stumm, PhD, Sophie Cave
Title of project: 
Family background and the intergenerational transmission of educational attainment: A multi-cohort analysis
Proposal summary: 

The overall aim of this project is to study how family background influences children’s attainment. We are interested in two questions. The first question is, how do ‘nature’ and ‘nurture’ combine to influence children’s attainment? To answer this question, we will test whether parental education-associated genetics are associated with the quality of parenting they provide to their children. We will test associations with parental behaviour from before a child is born (e.g., smoking, alcohol use during pregnancy), through infancy (e.g. breastfeeding), childhood (e.g. warm, sensitive parenting; cognitive stimulation), and adolescence (e.g. parental monitoring). We hypothesise that parents’ education-associated genetics are positively associated with these changing forms of parental investment across time. These analyses are a replication and extension of two previous papers from our lab (Wertz et al., 2018; Wertz et al., in press). In the proposed study, we will extend our previous work by a) analysing parenting across a wider age range of the child; b) replicating prior findings across several datasets (including ALSPAC); and c) incorporating measures of genetics and parenting from both mothers and fathers. The second question is, how do links between family socioeconomic status (SES) and children’s educational attainment change across time? To answer this question, we will test if the influence of family SES on children’s school performance has remained stable in Britain over time. We will test associations between family SES and children’s educational attainment across childhood, and compare estimates across different cohorts -- including ALSPAC -- from different historical periods. We hypothesise that the effect of family SES on children’s education will be relatively stable across time. Overall, this project will advance our understanding of the intergenerational transmission of educational attainment.

Impact of research: 
We believe this research will have impact in at least three ways. First, this research will create a better understanding of how genes and environments work together to shape child development. Second, this research will provide insights about how changing educational systems within the UK affect links between family background and children's attainment. Third, this research will contribute to a better understand of the mechanisms underlying and modifying the intergenerational transmission of educational attainment.
Date proposal received: 
Wednesday, 13 May, 2020
Date proposal approved: 
Thursday, 14 May, 2020
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Parenting

B3533 - Association between childhood trauma cognitive styles and depression - 12/05/2020

B number: 
B3533
Principal applicant name: 
Alex Kwong | UoB
Co-applicants: 
Dr Rebecca Pearson, Meera Bazaz
Title of project: 
Association between childhood trauma, cognitive styles and depression
Proposal summary: 

Existing research on depression vulnerability shows that early experiences such as exposure to childhood abuse could leave “cognitive scars”, which could increase vulnerability in later stages of life. Childhood emotional maltreatment is found to be strongly associated with vulnerability to psychopathology in comparison to physical and sexual maltreatment.(1) Adolescents having experienced childhood maltreatment were shown to depict reduced positive spontaneous thought, a feature of ruminative thinking constituting a risk factor for depression.(2) However, the role of mediating factors like cognitive styles in the association between childhood trauma and depression could be further explored. Various trauma types excepting physical neglect, predict depressive rumination, which predicts depression.(3) The differential association between age of exposure to trauma or specific trauma types and depression could be further researched as exposure to trauma in adolescence may have a greater effect size than that during early childhood with regard to developing increased odds of psychotic experiences. Examining the influence of mediating factors could be beneficial for preventing mental health issues such as distress and impairment at the population level by targeting negative cognitive styles.(4) Age groups requiring further support and intervention could be identified for addressing specific types of childhood trauma

Impact of research: 
Impact on policy/insight into mechanisms
Date proposal received: 
Thursday, 7 May, 2020
Date proposal approved: 
Tuesday, 12 May, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B3534 - Depressogenic thinking in adolescence and depressive mood across early adulthood - 12/05/2020

B number: 
B3534
Principal applicant name: 
Alex Kwong | UoB
Co-applicants: 
Dr Rebecca Pearson, Anugraha Chandraekaran
Title of project: 
Depressogenic thinking in adolescence and depressive mood across early adulthood
Proposal summary: 

Depression has become a common mental illness, and It is crucial to establish and study depressive symptoms through early adolescence across adolescence to early adulthood. It is vital to characterize specific causes and certain types of depression in populations to help identify critical points for intervention and treatment. Studies on Depressogenic thinking (i.e., negative cognitive styles) in early adolescence suggest there is an association with the development of depressive mood in this age group. However, the long-lasting effect of depressogenic thinking is not known, especially in early adulthood or later ages. This project will examine how different profiles of depressogenic thinking are associated with varying types of depression and depressive mood (e.g., irritability, anhedonia, depressive thoughts, fatigue or sleeping) and identify the mechanisms underlying negative thoughts (styles) and later depression. Although CBT and medication are used in treatment for diagnosed cases of depression, this study may potentially develop early intervention strategies that may target early adolescence to improve depressogenic thinking to prevent depression in early adulthood and beyond.

Impact of research: 
Could help elucidate mechanisms underpinning depression
Date proposal received: 
Thursday, 7 May, 2020
Date proposal approved: 
Tuesday, 12 May, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B3536 - Effect of adverse childhood experiences on adolescent depression anxiety and self harm An analysis in the ALSPAC cohort - 12/05/2020

B number: 
B3536
Principal applicant name: 
David Troy | University of Bristol (UK)
Co-applicants: 
Meghana Ratna Pydi, Dr Robyn Wootton
Title of project: 
Effect of adverse childhood experiences on adolescent depression, anxiety and self harm: An analysis in the ALSPAC cohort
Proposal summary: 

Adverse childhood experiences (ACEs) have been consistently linked to psychiatric difficulties in adolescents. Individuals with at least 4 ACEs are at four times the risk of experiencing mental distress and disorder in their lives. ACEs have been estimated to contribute to approximately 30% of cases of anxiety and 40% of depression in adults in a North American sample and more than a quarter for both conditions in Europe. The combined annual costs of depression and anxiety attributed to ACEs were approximately $51 billion in Europe and $82 billion in North America. Adolescence is a tumultuous time, with significant life events and high rates of mental disorder occurring during this life stage. It is essential to assess the effect of exposure to ACEs on the severity of mental disorders at this stage in the life course.

Impact of research: 
Date proposal received: 
Monday, 11 May, 2020
Date proposal approved: 
Tuesday, 12 May, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity, Parenting

B3537 - Relationship between early school experiences and adolescent self harm an analysis using the ALSPAC birth cohort - 12/05/2020

B number: 
B3537
Principal applicant name: 
David Troy | University of Bristol (UK)
Co-applicants: 
Miss Nitika Nitika, Dr. Judi Kidger
Title of project: 
Relationship between early school experiences and adolescent self harm: an analysis using the ALSPAC birth cohort
Proposal summary: 

Improving the mental health of children and young people is a national priority in the UK. The rate of self-harm amongst adolescents ranges from 6.9 to 18.8 % in the UK. Schools can provide an environment that encourages positive mental health at an early age and prevents poor mental health in later years. Positive relationships with peers and positive perceptions of school connectedness (that is, adolescents’ sense of belonging and attachment to school) are associated with increases in adolescents’ psychosocial wellbeing and decreases in the number of mental health issues. School absenteeism is also associated with an increased risk of self-harm. Levels of school absenteeism may be reduced if early school experiences are of a positive nature. There is also an association of suicidal and non-suicidal self-harm with adverse experiences at school and even minor events like not enjoying school or class work and the feeling about teachers being unclear with respect to their behaviour. We will investigate if early school experiences are associated with adolescent self-harm in the ALSPAC cohort.

Impact of research: 
Date proposal received: 
Monday, 11 May, 2020
Date proposal approved: 
Tuesday, 12 May, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Social science, Statistical methods

B3538 - Early metabolic features of adiposity-related cancer susceptibility - 12/05/2020

B number: 
B3538
Principal applicant name: 
Joshua Bell | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Dr Caroline Bull, Dr Emma Vincent, Prof Nicholas Timpson, Dr Marc Gunter
Title of project: 
Early metabolic features of adiposity-related cancer susceptibility
Proposal summary: 

Cancers develop for many years before they are diagnosed. Using data from first-generation ALSPAC offspring, we aim in this study to estimate the effects of being more genetically susceptible to obesity-related cancers that commonly emerge in adulthood on metabolic traits measured in blood across early life; this should help to reveal what early stages of cancer development look like and when they occur. More specifically, we will examine associations of genetic risk scores for different cancers that are known to be influenced by obesity, e.g. colorectal cancer, with traits from targeted metabolomics measured in childhood (age 8y), adolescence (age 15y), and young adulthood (age 18y and 25y). This allows us to view subtle changes in metabolism over time which precede the onset of clinically detectable cancer by several decades. Recognizing the early signs of cancer development is vital for informing early detection, preventing its onset in older age, and improving survival.

Impact of research: 
The likely output of this research will be at least one publication in a general medical or epidemiology journal, the impact of which may be theoretical advancement in active research fields of metabolism and cancer, and recommendations for clinical practice.
Date proposal received: 
Monday, 11 May, 2020
Date proposal approved: 
Tuesday, 12 May, 2020
Keywords: 
Epidemiology, Cancer, Metabolomics, Metabolic - metabolism

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

B3529 - Exploring the text data provided by participants completing the COVID Q - 07/05/2020

B number: 
B3529
Principal applicant name: 
Kate Northstone | University of Bristol (United Kingdom)
Co-applicants: 
Dr Katrina Turner, Dr Lucy Biddle
Title of project: 
Exploring the text data provided by participants completing the COVID Q
Proposal summary: 

In response to the COVID-19 pandemic, a questionnaire was put together and sent out to ALSPAC participants. A number of free text responses have been collected as part of that questionnaire and that data will be immensely valuable in understanding the circumstances of the participants during the pandemic. We plan to code this data in order to make the data usable in quantitative analyses and explore recurring themes in this additional data.

Impact of research: 
The text data is telling us additional stories that we are not obtaining from the questionnaire tick box data alone. It is therefore vital it is taken into account as best we can to inform analyses undertaken using the data.
Date proposal received: 
Tuesday, 5 May, 2020
Date proposal approved: 
Thursday, 7 May, 2020
Keywords: 
Epidemiology, Mental health, Qualitative study

B3531 - Socioeconomic inequalities in mental health and cognitive trajectories - 07/05/2020

B number: 
B3531
Principal applicant name: 
Tim Cadman | University of Bristol (UK)
Co-applicants: 
Deborah Lawlor, Laura Howe, Kate Northstone
Title of project: 
Socioeconomic inequalities in mental health and cognitive trajectories
Proposal summary: 

Whilst it is established that children of lower socioeconomic position (SEP) generally have worse mental health outcomes, most existing research is cross-sectional. Longitudinal studies are important for understanding when inequalities first emerge and the course they take (e.g. stable, widening or decreasing). Whilst longitudinal approaches are now commonly used to model inequalities in height and weight they have rarely been used for mental health outcomes. The aim of this project is use data from multiple EU studies to describe how inequalities in key mental health and cognitive outcomes emerge across childhood.

The aim of this project is to investigate the effect of socioeconomic position on trajectories of key mental health and cognitive outcomes across childhood. It will also serve as a ‘proof of concept’ for using DataSHIELD to conduct multilevel analyses. Our specific aims are to (1) to identify the age at which inequalities emerge for different mental health outcomes, and (2) to describe whether inequalities decrease, remain stable, or widen over time.

Impact of research: 
Greater understanding of how socioeconomic inequalities emerge across childhood, which outcomes show greater social patterning and how inequalities differ across Europe
Date proposal received: 
Wednesday, 6 May, 2020
Date proposal approved: 
Thursday, 7 May, 2020
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Mental health, Statistical methods, Childhood - childcare, childhood adversity, Development

B3528 - Transmission Distortion in the Human Genome - 07/05/2020

B number: 
B3528
Principal applicant name: 
David Evans | University of Bristol; University of Queensland
Co-applicants: 
George Davey Smith, Dr Gib Hemani, Shannon D'Urso, Dr Alex Havdahl, Dr Gabriel Cuellar Partida, Dr Neil Davies, Dr Laurence Howe
Title of project: 
Transmission Distortion in the Human Genome
Proposal summary: 

Transmission distortion refers to deviation from the normal 50:50 transmission of alleles from parents to offspring. Departures from this ratio can arise from a number of processes including ‘meiotic drive’ where one allele is preferentially transmitted during meiosis, differences in the fertility or viability of gametes, differences in the survival of the embryo, and artefacts due to the selection of the study sample. The identification of loci which exhibit transmission distortion is not only of substantial biological interest, but is also desirable for the correct interpretation of genetic linkage and association studies.

NB. To be clear we already have the ALSPAC GWAS data required to perform the analyses listed as part of this project and so do not need to be sent any additional data. We are merely requesting permission to conduct analyses and for new staff to access the data.

Impact of research: 
Date proposal received: 
Tuesday, 5 May, 2020
Date proposal approved: 
Thursday, 7 May, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), GWAS, Genetic epidemiology, Genetics, Genome wide association study, Offspring

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

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.

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

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

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

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