Proposal summaries
B3623 - The impact of Adverse Childhood Experiences on social and health inequalities a life course perspective - 06/10/2020
Adverse Childhood Experiences (ACEs) are stressful events that occur during childhood and adolescence, and include child maltreatment (i.e. emotional, physical, and sexual abuse and neglect) as well as measures of family dysfunction (e.g. parental divorce/separation, intimate partner violence, substance misuse, mental illness, and imprisonment). People who experience ACEs are less likely to do well in school, more likely to become unemployed, and more likely to have poor health. Furthermore, since people who live in socioeconomic deprivation are more at risk of experiencing ACEs, and also more at risk of poor health, ACEs are one mechanism that could drive socioeconomic inequalities in health. However, most of the research to date has looked at ACEs as a whole, and not asked whether experiencing ACEs at different points during infancy, childhood and adolescence might have different impacts. This is important, because it affects decisions about how we best support people who experience ACEs. If ACEs in infancy have the biggest effect on later outcomes, then focusing support on the early years will be most beneficial. Whereas if ACEs at older ages also cause problems, potentially ‘derailing’ people from their previous educational level for example, that would imply that continued support across the whole of childhood and adolescence is important. At a time when local government budgets are severely stretched, generating evidence to help support the justification and prioritisation of interventions is crucial. At present, our ability to carry out high-quality cost-effectiveness analysis of interventions to mitigate the effects of ACEs is limited by a lack of good evidence on the effects of ACEs on key economic outcomes, and how these effects differ across the life course. In this project, we will plug this gap, using extremely detailed data about experiences of ACEs across the life course, linked with detailed family and socioeconomic data, and repeated measures of educational attainment, employment, and health. We will explore the links between ACEs and education and employment, whether these are affected by the timing, duration and recency of ACE exposure, and the mechanisms underlying the associations.
The 2020 SARS-Cov-2 pandemic is likely to have severe implications for children experiencing ACEs and adults who have experienced ACEs. The ‘lockdown’ measures are likely to lead to increased occurrence of ACEs. Missed schooling is likely to be more detrimental for already vulnerable children, and many children who were entitled to continue attending school during lockdown did not do so. Job losses and reductions in income have been concentrated in the already disadvantaged, and the uncertain job market going forwards will pose a greater risk to young adults without the cushioning of a stable family environment and educational success. Using new data collected during the pandemic, we will assess whether young adults who have experienced ACEs are more vulnerable to the economic consequences of the pandemic, e.g. reduced income, furlough, or job loss. This evidence could provide support to the continued and increased need for the provision of services for people experiencing ACEs at this time.
We will work with key academic and non-academic collaborators to ensure that the results from this project are used to support the case for services designed to support people who have experienced ACEs, including with our results being used directly to improve the quality of cost-effectiveness analyses for interventions.
B3618 - The role of genetics in body size at different life stages longitudinal study in ALSPAC - 29/09/2020
B3617 - Association of maternal thyroid dysfunction with cardiometabolic traits in offspring - 05/10/2020
Previous studies have demonstrated that maternal thyroid dysfunction is associated with a number of neurodevelopmental disorders, such as attention deficit hyperactivity disorder and epilepsy. However, the association between maternal thyroid dysfunction and other health outcomes in offspring were either investigated in single study, or not examined. One single study conducted in 998 maternal-child pairs in Canada demonstrated that maternal hypothyroidism was associated with increased risk of congenital heart disease (CHD) in offspring (OR=1.68; 95% CI: 1.02-2.78). Another retrospective cohort study showed that children born to mothers with hypothyroidism have increased risk of hypoglycemia (RR=2.9; 95% CI: 1.4-6.2) and total endocrine morbidity (RR=2.1; 95% CI: 1.2-3.8). It was also observed that offspring of mothers with subclinical hypothyroid during the third trimester of pregnancy had higher systolic blood pressure. It remains unclear if the above associations exist in other populations. Whereas, inconsistent findings were observed for the risk of diabetes in children born to mothers with various thyroid diseases. It is known that thyroid dysfunction in adults may affect a number of cardiometabolic traits. This project aims to evaluate the observational and causal association between maternal thyroid dysfunction and various cardiometabolic traits in offspring.
B3619 - Depositing data with DPUK a trial dataset - 22/09/2020
As part of our commitment to DPUK (https://www.dementiasplatform.uk/) we are developing a trial dataset to be classified using the DPUK ontology and for the variable list to be uploaded to the DPUK data portal. Further developments may take place if hte trial proves successful.
B3616 - Implications of covid-19 lockdown for inequalities in health student mini project - 22/09/2020
Stark inequalities in health already exist in the UK, with people from lower socioeconomic backgrounds suffering from greater levels of ill health across multiple domains. The covid-19 pandemic potentially threatens to worsen these health inequalities. The ‘lockdown’ changed people’s behaviour radically, but the socioeconomic differences in these experiences are not well understood. Some groups of society may have increased health-promoting behaviours – for example, engaging in more physical activity and preparing more food within the home. Other groups may have experienced adverse changes in health-related behaviours – for example, smoking more or consuming more alcohol in response to the stress and anxiety induced by the pandemic. It is possible these differences are socioeconomically patterned, and could therefore worsen pre-existing inequalities. Another key factor likely to influence patterns of behaviour change during the pandemic is household/family structure. For example, parents with children and individuals shielding or living with a household member who was shielding may have been less able to engage with health-promoting behaviours.
Data from the Office for National Statistics demonstrate that between 23rd March and 5th April 2020, 27% of the UK workforce were furloughed due to the COVID-19 lockdown. Many others lost jobs, or had working hours and income reduced. The adverse financial and employment consequences of the covid-19 lockdown are concentrated in already vulnerable groups of society – they are more likely to be experienced by people in insecure or low-paid jobs. The young adults in ALSPAC are in the age groups most likely to have been affected by furlough, job losses, and loss of pay or hours (https://www.resolutionfoundation.org/publications/young-workers-in-the-c...). Detailed pre-pandemic data from the ALSPAC cohort offers the opportunity to better understand which groups of society were more likely to be impacted financially by the lockdown. We will explore whether SEP, adverse childhood experiences, pre-existing mental health problems, obesity, smoking, alcohol use, shielding or living with a household member who was shielding, and family structure are associated with greater likelihood of adverse financial changes during covid-19, and hence whether the lockdown is likely to exacerbate health challenges for these groups.
B3615 - Research-on-research Blinded data analysis to improve the robustness and reproducibility of health research - 08/10/2020
Bias in scientific research can lead to research waste and useless or even harmful health care and policy interventions. To reduce bias, researchers commonly employ experimental designs that blind both participants and outcome assessors. Data analysts, however, are rarely blinded. Here, we propose to test whether blinding data analysts improves the reliability of published research findings. To execute the study, we will randomize researchers who request the Avon Longitudinal Study of Parents and Children (ALSPAC) dataset, and consent to partake in the research, to receive either data from only 10% of participants, or data from all participants. Researchers who receive 10% of the data will develop their analysis based on this subset and be asked to register their analysis plan. After registering their analysis plan, the full dataset will be provided. We call this “Blind Access”. Researchers who receive the full dataset will not be required to register their analysis. We call this “Standard Access”. We will then compare the reliability of the published findings between the Blind Access and Standard Access groups.
B3613 - Deep phenotyping of cardiovascular systems physiology in adults born to hypertensive pregnancies - 10/09/2020
New-onset hypertension during pregnancy occurs in up to 10% of women. People born to pregnancies complicated by hypertension (i.e. gestational hypertension and preeclampsia) are at increased risk for cardiovascular disorders, including hypertension and stroke, in later life. The underlying disease process is identifiable in the first decades of life with evidence of emerging damage to their hearts and blood vessels. Phenotypic changes that have been observed in early postnatal life and as they reach young adulthood include higher blood pressure, altered heart structure and function, as well as a reduced number, size, and function of small blood vessels. However, to date, longitudinal data in the same individuals, as well as a multi-systems, deep phenotyping approach to characterizing cardiovascular physiology in offspring of hypertensive pregnancies, remains limited. By using ALSPAC, we will be able to make use of the previously collected demographic, anthropometric, and phenotypic data collected. We will also design a new study in 200 young adults, of which 100 will be born to hypertensive pregnancies and 100 born to normotensive pregnancies. These participants will be invited by the ALSPAC team to travel to Oxford for a 3 hour study visit, including blood sample collection, exercise stress testing, blood pressure and imaging of the small blood vessels in the eye, brain MRI, as well heart scans using both MRI and echocardiography at rest and during exercise. By studying and tracking changes both temporally and spatially across multiple organs, we will be able to better describe and quantify the multi-dimensional landscape of hypertensive disease progression.
B3612 - Using detailed cohort data to investigate collider bias in mental health outcomes - 08/09/2020
The need for comprehensive and representative data collection on populations for epidemiological research has been brought into sharp focus by the COVID-19 pandemic. This has resulted in the generation of many COVID-specific modules within existing cohorts and datasets (e.g. Henderson et al, 2020, Kwong et al, 2020). These datasets are going to be invaluable in understanding the mental health response of individuals to the COVID-19 pandemic. These studies reflect individuals responding under unique circumstances, presenting unique selection effects, which have the capacity to substantially bias results (Griffith et al. 2020). These selection effects are likely to be particularly stark with respect to mental health, which is known to be associated with non-response (Kwong, 2019). The data and analysis will be carried out by GG and DS, and data stored on the University of Bristol RDSF.
B3608 - Do poverty-reduction fiscal policies reduce childhood obesity A study based on microsimulations and scenario evaluations - 29/09/2020
B3610 - Understanding the relationship between autism and personality disorder an epidemiological study - 04/09/2020
People with autism and those with personality disorder often experience difficulties in understanding and responding to their emotions and managing relationships with others. The overlapping nature of these symptoms means that health professionals sometimes find it difficult to distinguish the presence of autism from personality disorder in an individual. To date, very little research has examined the diagnostic overlap between autism and personality disorder and the potential links, as well as the differences between these two conditions, are not well understood. For example, it is unclear whether any features of autism are associated with the future development of personality disorder.
We propose to undertake the first robust scientific study of these issues, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a world leading cohort study. We will accelerate knowledge in the field by clearly establishing whether a link exists between autism and personality disorder. We will explore a wide range of biological, psychological and social factors that might be driving the association, ranging from genes through to the experience of being bullied as a child. Our study has the potential to make a difference to the lives of people with personality disorder and autism. This is because the knowledge that we will develop about the potential pathways between autism and personality disorder will improve the support and care offered to people with these conditions in the future.
B3600 - Investigating the effects of autism related exposures on BMI and disordered eating behaviours in adulthood - 02/09/2020
Autism is a lifelong condition characterised by difficulties with social interaction, social communication and repetitive behaviours. In recent decades, the number of children and adults diagnosed with autism has increased. As autism is heritable, genetic risk may explain why there are some individuals with mild autistic traits but they may not meet the criteria for an autism diagnosis and subsequent treatment or other support requirements. As more children with autism and mild autistic traits reach adulthood, the need for support from health and other services will likely increase. However, few large, population based longitudinal studies involving adults with autism/autistic traits exist, representing a research gap.
During this phase of my PhD project, I will study how autism and autism traits, including genetic risk for autism, may be associated with BMI and disordered eating behaviours in adulthood. Children with autism often having sensory issues and unusual eating preferences, which could have an effect on growth and health in adult life. It has been reported that social communication difficulties may increase the risk of disordered eating patterns in adolescence. This implies that maintaining a healthy BMI may be challenging during this period and that there is a possible increased risk of disordered eating behaviours and eating disorders in adulthood for those with social communication difficulties. This phase of my PhD project is focussed on whether autistic individuals are more likely to have high BMI and disordered eating behaviours in adulthood. Changes in growth during late childhood into late adolescence will also be studied to assess whether there are critical periods that are suitable for intervention.
B3607 - The relationship between sedentary time sedentary patterns and cognitive functions in adolescents and young adults - 02/09/2020
Previous research has shown that time spent viewing TV or in self-reported sedentary behaviors is related to suboptimal cognitive functioning in older adults. However, not all sedentary behaviors show negative relationship with cognitive functions and most studies focused on leisure time sedentary behaviors. Consequently, these studies were unable to assess the relationship between daily volume of sedentary time and cognitive functions. Physiological adaptations to sedentary lifestyle include adverse cardio-metabolic profiles and low-grade inflammation. These physiological responses contribute to suboptimal brain and cognitive functions. Chronic stress has been negatively related to cognitive functions in youth and adults. Socio-economic status is one of the correlates of sedentary behaviors and higher levels of chronic stress have been observed among individuals with low socio-economic status. Thus, individual differences in chronic stress may help explain the associations between sedentary time, physical inactivity and suboptimal cognitive functioning. Furthermore, it is important to ascertain which biological pathways may be specific to excessive engagement in sedentary time. Adolescence and young adulthood are the most opportune periods to study these relationships due to low prevalence of chronic disease and comorbid conditions compared to middle-aged and older adults, high levels of sedentary time (adolescents are the most sedentary group after older adults, and European adolescents spend on average 7.5 hours per day sedentary) and protracted development of higher order cognitive functions yielding them amenable to behavioral interventions during these developmental periods.
B3605 - Genetic influences on infant and childhood growth - 02/09/2020
The obesity epidemic is one of the most important health challenges of the 21st century.
Identifying genetic factors predisposing to weight gain is crucial for identifying biological processes important for weight-control and help identify individuals already at young age that might benefit from health interventions and thereby reducing their risk for disorders such as type 2 diabetes that follow in its footpath.
While there is great progress deciphering the genetic factors influencing weight in in adulthood, and at birth, there is a huge knowledge gap on the role of the genomes of the child and its parents in infancy and childhood into puberty. This is very unfortunate, as it is firmly established that the BMI-development during the first 6 years of life are strong predictors of obesity in adolescence . Results from our own ongoing work in the Norwegian Mother, Father and Child and work of others show that it is possible to find novel genetic variants with specific and substantial effect on weight development during infancy with high quality data and large GWAS sample sizes.
B3604 - Positive and adverse childhood experiences and cardiovascular disease risk - 25/08/2020
Cardiovascular diseases (CVDs) are a significant public health concern and are a leading cause of mortality, representing 31% of all global deaths in 2017. These diseases often have their origins in childhood. Ample evidence suggests that exposure to childhood adversity, such as experiences of violence, parent imprisonment, household mental illness or substance use, has harmful effects on cardiovascular and other non-communicable diseases. Experiencing two or more adversities is associated with higher risk of cardiovascular disease in Europe and North America, respectively, corresponding to US$150 and US$164 billion in associated costs. Whilst there is evidence that adverse childhood experiences are associated with higher cardiovascular risk, whether socioeconomic inequalities in cardiovascular risk might be explained by childhood adversities. Understanding the extent to which adverse experiences in childhood could potentially explain socioeconomic inequities in CVD risk would help to inform the targeting of resources.
Further, the milieu of the family environment includes not just adverse experiences, however, but also positive experiences, which have been understudied. Positive experiences do not simply reflect the absence of risk factors, but instead are independent attributes or assets that enhance health and resilience over time. For example, the absence of abuse in the household does not necessary imply optimal parenting. The Health Outcomes from Positive Experiences (HOPE) is a complimentary framework to childhood adversity that organises positive childhood experiences into four broad categories: Being in nurturing, supportive relationships; Living, developing, playing, and learning in safe, stable, protective, and equitable environments; Having opportunities for constructive social engagement and to develop a sense of connectedness; and Learning social and emotional competencies.
Emerging evidence suggests that positive childhood experiences â variably defined â are associated with better adult cardiovascular health. These studies are suggestive that positive experiences in childhood also have relevance for cardiovascular health. To fully understand childrenâs experiences in the early years and how environments can be optimised to promote cardiovascular health in later life, however, we need to capture both adverse and positive experiences in childhood; otherwise, we just look at half the picture. For example, no previous studies have examined whether the effect of positive experiences was evident over and above that of adverse experiences in childhood. While adverse and positive experiences are not the inverse of one another, they are negatively correlated. Do positive experiences actually matter for cardiovascular health, or are they just a proxy indicator for the absence of adverse experiences? If they do matter, can they help to promote resilience in the presence of childhood adversity; that is, good health despite the presence of adversity?
B3606 - Genetic determinants of neonatal hyperbilirubinemia - 25/08/2020
Neonatal jaundice is a yellowish discoloration of the eyes and skin in a newborn baby as a consequence of high bilirubin levels. While jaundice in most newborn is normal, a subset of patients with elevated bilirubin levels may develop excess sleepiness or poor feeding, whereas patients with excessive bilirubin levels are at risk for severe brain damage. In this project we aim to identify genetic risk factors for the development of high bilirubin levels in the newborn. This information can aid in risk prediction and the onset of early treatment for hyperbilirubinemia in the newborn.
B3601 - The genetic basis of acne vulgaris - 02/09/2020
B3317 - Visual Impairment in Psychosis Cause Consequence or Biomarker - 25/08/2020
Eyesight Problems and Psychotic Illnesses: Whatâs the Link?
Psychotic illnesses affect just under 1% of people in England. Symptoms include hearing voices and experiencing confusing and distressing thoughts. These often begin in early adulthood, and can have a major effect on peopleâs lives.
People with psychotic illnesses seem to have more eyesight problems. We are not sure why, but it might be because:
⢠Possibility 1: Some people with psychotic illnesses find it harder to look after their health including their eyes, for example by going to the opticianâs.
⢠Possibility 2: The same brain changes cause eyesight problems and psychotic illnesses.
⢠Possibility 3: Eyesight problems increase a personâs chances of having a psychotic illnesses.
I plan to look at which of these best explains the link between eyesight problems and psychosis. If people with psychosis have less eye care (possibility 1), we need to improve this. If possibility 2 is correct, eye research might hold the key to understanding more about the brain changes that cause psychosis. Or, if eyesight problems lead to psychosis, then improving eye health could be a way of preventing or reducing psychosis.
I will start by reviewing past research, to make sure I base my work on the most up-to-date information. I will then carry out research using two large datasets: UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC).
UK Biobank has information on over half a million 40 to 69-year-olds including questionnaires, eyesight tests and genetic tests.
ALSPAC has information on 14,500 UK families. The children have been followed up since before birth and will be 25.
I will look at UK Biobank and ALSPAC because older and younger people are most at risk of developing psychosis. In these datasets, I will see if people with short-sight genes have more psychotic illnesses. If so, this would be evidence that poor eyesight can lead to psychosis. Genes are present before birth, so I will know that they came before any psychotic illness began. I will also find out if genes for psychotic illnesses are linked with eyesight problems. This would suggest the reverse: that psychosis leads to poor eyesight.
I will also use a third, Israeli dataset. All Israeli 17-year-olds have health checks to decide if they can join the armed forces. I will use this data to find out if teenagers with eyesight problems are more likely to have a psychotic illness over the following years. If so, I will see what level of eyesight problems are associated with developing psychosis. This will allow me to test the theory that perfect eyesight and complete blindness both protect against psychosis, with moderate eyesight problems carrying the highest risk.
Throughout this research, I will chair a group every 6 months. It will include people with psychosis, people with eyesight problems, carers, charity members and doctors. We will discuss study findings and think about how to use them to improve the experiences of people with eyesight problems and psychosis. This will include plans to publicise findings, influence healthcare and plan new studies.
When the research is finished, I will tell healthcare professionals and researchers about the results at meetings and in journals. I will also write about them in publications read by people with mental health and eyesight problems. I will offer to present findings to public groups, through links with the Royal National Institute for the Blind (RNIB) and a forum of mental health service users.
People with eyesight problems and mental health service users helped to write this summary.
B3602 - Linking observed mental health data with record linkage in ALSPAC - 21/08/2020
The purpose of this project is to provide additional data for the project B3550 (antidepressant use and mental health) and collect new data as part of ALSPAC's mental health response to the COVID-19 pandemic. This data will allow further examinination for the ongoing mental health work by ASPAC and can be used alongside record linkage data to examine patterns of mental health before and during the COVID-19 pandemic. We are interested in examining if observed data from COVID-19 and the annual Questionnaire match patterns taken from health record data (i.e., are people who report poorer mental health accessing services). If these patterns do not match, it is important to determine why not and how people with poorer mental health are managing if not by accessing services. This will provide insights into alternative forms of treatment for poorer mental health in the pandemic. We have three main objectives. The first is to further describe patterns of mental health by building upon our earlier work using COVID 19 mental health data. The second is to link the observed mental health data with the health record linkage and examine outcomes from the COVID-19 pandemic. The third is to provide additional data for B3550.
B3598 - Psychosocial mechanisms of persistent pain Expression of Interest - 28/08/2020
The remit of the Advanced Pain Discovery Platform funding call is to better understand the mechanisms associated with pain. Our Expression of Interest is focused on psychosocial mechanisms of pain, and as part of this we wish to see how these impact on individuals across the lifespan. We wish to explore potential psychosocial correlates of pain, and build on work already conducted by members of our consortium on pain. Details of this project will be updated in due course.
B3597 - Resilience and Susceptibility to Chronic Pain in ALSPAC - 28/08/2020
Pain which lasts for more than 3 months is termed chronic or persistent pain. It often occurs in the absence of obvious injury. It can be very difficult to treat. The UK is home to several large databases that contain information about subjectsâ life history of pain and their genetic âmake-upâ. We plan to use the largest of these (UK Biobank) to help identify the genes that are related to the presence of a chronic pain condition (e.g. pain of duration >3 months) and the related symptoms experienced by sufferers e.g. low mood, poor sleep, lack of motivation, (pain) anxiety or pain depression. By gaining confidence that these genetic markers are related to the presence of a chronic pain condition, we will then use this information to recruit two small (each <200) groups of ALSPAC subjects who may or may not already have a pain condition. The beauty of this approach, is that by identifying the genes that make people susceptible to developing a pain condition, we will see how this interacts with health factors e.g. weight, blood pressure, and events that shape a personâs psychology e.g. adverse life events such as bereavement, to try to provide a means for people to modify their risk, or identify people for whom early intervention might be most beneficial following an injury â to hopefully avoid them going on to suffer life-long pain.
To achieve this goal, we would ask those subjects to undergo a series of pain tests (which of themselves cause only temporary discomfort) and undergo an MRI scan of their brain and spinal cord.
To better characterise pain present in the ALSPAC cohort, we propose to add pain-specific questionnaires (and tasks) to the upcoming age 30 clinics and questionnaires, which would target all participants. These questionnaires/tasks would explore the incidence of pain in the cohort, which will provide a more complete picture than is currently available. By adding information to this time point, we will gain insight to the cohort and to which genetic and biological factors can influence the development of a chronic pain condition. The availability of this window, where the majority of the cohort are still (hopefully) pain-free, will provide a baseline from which future studies will be able to reflect on the factors that ultimately led some participants to develop a chronic pain condition.