Proposal summaries
B3579 - Associations of COVID-19 Risk Perceptions with Mental Health Wellbeing and Risk Behaviours - 24/07/2020
Risk perceptions are subjective judgements that people make about the characteristics and severity of a risk (Darker, 2013), and they can influence emotions and behaviours (Ferrer & Klein, 2015; Paek & Hove, 2017). Accuracy is critical; underestimating or overestimating the level of threat and danger can have negative consequences. For example, underestimation of risk in a pandemic can reduce adoption of protective and preventative health behaviours (Dryhurst et al., 2020; Khosravi, 2020; Leppin & Aro, 2009). While overestimation of risk can increase hoarding behaviour, potentially leading to shortages of medications and personal protective equipment (Abrams & Greenhawt, 2020). Overestimation of risk may also lead to reluctance to return to normal activities as national lockdowns ease.
As well as influencing behaviour, risk perceptions can negatively impact mental health and wellbeing. Among young adults in the Avon Longitudinal Study of Parents and Children (ALSPAC), wellbeing has reduced, and anxiety levels have almost doubled during the COVID-19 pandemic, compared to pre-pandemic levels (Kwong et al., 2020). This is an important public health issue, given that anxiety is associated with maladaptive coping strategies such as increased alcohol use (Dyer, Heron, Hickman, & Munafò, 2019). High risk perceptions may be one factor associated with this increase in anxiety and reduction in wellbeing. In this project, we will examine the bi-directional associations of COVID-19 risk perceptions with mental health, wellbeing, and risk behaviours, using genetic and self-report data. It is also important to examine the mental health and behavioural precursors of COVID-19 risk perceptions, given their influence on health behaviours.
B3581 - Dissecting PCOS Physiology by Defining Phenotypes Associated with PCOS Genetic Risk Factors in Children - 24/07/2020
Polycystic ovarian syndrome (PCOS) is a major health concern that affects up to 10% of reproductive-aged women. This complex, heterogeneous condition is often characterized by a triad of ovulatory dysfunction, hyperandrogenism, and cardiometabolic dysfunction. Despite extensive physiologic and genetic studies, the treatment of PCOS remains limited by an incomplete understanding of the pathophysiology of the disorder. Identification of the genetic variants and pathways associated with PCOS susceptibility may provide insights into the pathogenesis of the condition and potential targeted treatments.
We propose to study phenotypes in children that may be associated with PCOS, including obesity, dyslipidemia, and premature adrenarche. Premature adrenarche is a pediatric condition characterized by early production of adrenal androgens such as DHEAS and androstenedione and has been proposed to be a precursor to PCOS in girls. We will calculate a polygenic risk score for PCOS in prepubertal children and test for associations with premature adrenarche and associated cardiometabolic and hyperandrogenic outcomes and biochemical and anthropometric traits. In addition, we will examine these outcomes during the pre-pubertal period in girls who later develop a diagnosis of PCOS in adolescence and young adulthood.
The extension of PCOS genetics to prepubertal children provides the unique opportunity to 1) classify the PCOS pathways into ovarian-dependent factors and nonovarian-dependent factors and 2) characterize the pediatric phenotypes associated with PCOS genetic risk factors, and 3) understand the pre-pubertal manifestations of a future PCOS diagnosis. Overall, investigations in prepubertal children have the potential to provide valuable insights into the mechanisms of pathogenesis and targets for treatment for PCOS.
B3577 - Understanding the relationship between adverse childhood experiences and later mental health outcomes - 23/07/2020
Adverse childhood experiences (ACEs) such as abuse, bullying or family disruption are increasingly recognised as one of the most potent determinants of later mental health problems. Estimates suggest that mental health problems, including depression and self-harm are at least double among those who have been exposed to ACEs. Despite the recognised importance of ACEs to later mental health outcomes, relatively little is known about the characteristics of ACEâs that have the greatest impact. Firstly, many studies have relied on cumulative scores, whereby ACEâs are simply dichotomised and summed. This approach assumes that each ACE contributes equitably to the outcome of interest and that they operate via the same mechanisms. Other research has focused on the relationship between individual ACEsâ and mental health. Although such studies have provided useful insights, it is known that ACEâs often co-occur and most have failed to take account of this clustering. Person centred approaches such as Latent Class Analysis (LCA) could be used to identify variability in ACE profiles between individuals and investigate potential differential associations with mental health, demographic factors, and mechanisms. Secondly, little attention has been paid to the role of timing, chronicity, or recency of exposure in relation to mental health, and findings from existing studies have been inconclusive. Disentangling these effects is challenging as it may be that those who have been exposed earlier in childhood have also been exposed for longer. This PhD will address these limitations and generate valuable new insights into the relationship between ACEs and two mental health outcomes â depression and self-harm.
B3578 - Genetic and non-genetic influences on the development of psychiatric outcomes in children born with cleft lip and/or palate - 23/07/2020
Cleft of the lip and/or palate is a common birth defect worldwide and occurs at a rate of one in 650 live births in the UK. Being born with cleft places a significant burden on children, their families and the health system as they require surgery (multiple times depending on cleft type), and other interventions to improve appearance, speech, hearing, dentition and other adverse outcomes. They are also at increased risk of psychological, psychiatric and cognitive problems [1]. There are several possible mechanisms underlying these associations that may be operating alone or together. First, they may reflect the psychological, developmental and social impacts of clefting and its treatment. Second, they may reflect genetic factors either as pleiotropic outcomes of genetic susceptibility to clefting or as independently inherited genetic risk.
The aetiology of both cleft and of psychiatric disorders is complex, with common risk alleles [3] [4] of individually small effects as well as rare genetic mutations of large effect and environmental factors playing roles. One group of rare mutations of large effect are Copy Number Variants (CNVs), referring to deletion or duplication of a part of the genome leading to differences between individuals in the number of copies of genes within the affected region. CNVs are known to increase risk of neurodevelopmental disorders (ND-CNVs), such as ADHD and autism, as well as mental health disorders but the presence and the impact of CNVs have not been studied in cleft [5].
The PhD project will provide the first detailed description of neurodevelopmental and mental health outcomes in children with cleft and examine the contributions of genetic and environmental factors. For this we will use two unique genetically informative clinical cohorts of children; the Bristol University Cleft Collective and the Cardiff University longitudinal ExperiencCes of people witH cOpy number variants (ECHO) study. Control samples will consist of the Avon Longitudinal Study of Parents and Children (ALPSAC) and the Millennium cohort which are deeply-phenotyped cohorts of typically developing children.
B3580 - Investigating the Activity of Transposon-Derived Regulatory Sequences in the Human Placenta - 04/08/2020
The placenta is crucial for the initiation and maintenance of pregnancy. Common complications of human pregnancy, such as preeclampsia, often have unknown etiology but feature contributions from genetic and non-genetic causes. DNA exists in the cell bound by proteins and other molecules, forming a structure known as chromatin. The structural conformation of chromatin is just as important as the DNA code itself, since chromatin structure dictates which components of DNA are active, and therefore able to regulate the cell. Formalin-fixed placentas maintain the structural conformation of their chromatin, making them a uniquely valuable resource to identify the location and activity of regulatory DNA. My proposal seeks to investigate the causes of preeclampsia by comparing the chromatin structure in formalin-fixed placentas from control pregnancies and those complicated with preeclampsia. I will focus on regions of non-coding DNA that regulate gene activity, so-called gene promoters and enhancers, including a special subset of these regions known as transposons. Placental chromatin exhibits a unique structure compared to other tissues, featuring an open conformation around transposons, indicative of their activity in placenta. The activity of gene-regulatory DNA provides the basis of tissue and organ-specific developmental programs. As such, the development and function of the placenta is dictated by the activity of regulatory DNA, and structural variation at these regions can cause disease. I will test the hypothesis that chromatin structure variation of DNA regulatory sequences contributes to the causes of preeclampsia.
B3575 - Socioeconomic disparity placental pathology and child development - 07/10/2020
Socioeconomic disadvantage and stress are associated with adverse pregnancy and child health outcomes. There is some evidence to suggest that these associations may be mediated by changes in placental development and function. However, studies of the placenta are often small or limited to pathologic samples, which may not be representative. ALSPAC routinely collected placentas of participants, including term deliveries, and ALSPAC has rich parental sociodemographic information and longitudinal follow-up on child health and development. This presents a unique opportunity to estimate associations between socioeconomic disadvantage and child development and to examine the mediating role of placental pathology in a well-characterized, representative sample.
B3576 - Religious belief and reaction to Corvid-19 pandemic - 21/07/2020
To provide exemplar analyses for inclusion in a grant application
B3574 - Causes of Chronic Pain in ALSPAC - 28/08/2020
Pain which lasts for more than 3 months is termed "Chronic Pain". It often occurs in the absence of obvious injury. It can be very difficult to treat.
We believe that the body may produce antibodies (part of the natural defence against infections) that can activate "pain" nerves. This may contribute to Chronic Pain.
Antibodies, produced by the body are known to sometimes interfere with the nerves in diseases such as Myaesthenia Gravis.
If we can demonstrate that these antibodies can cause chronic pain, we will be able to treat patient with chronic pain much more effectively.
B3572 - Does attachment style in childhood predict mental health difficulties in early adulthood - 20/07/2020
Attachment theory explains social, relationship and personality development across the lifespan (Bowlby 1969) and has been shown to provide a psychological framework for understanding mental ill health (Mikulincer & Shaver, 2007). The basic postulation is that very early childhood social interactions with primary caregivers are internalised to create and maintain conscious and unconscious mental representations of the self and others. These form the basis of âattachment stylesâ, which have an impact on close relationships and ability to regulate emotions. There is extensive evidence that attachment style is a predictor of coping strategies, adjustment in response to stressors and therefore a vulnerability to mental health problems (see Mikulincer & Shaver 2012 for a review). Research has widely demonstrated an association between secure attachment style and well-being and positive mental health, whilst both insecure attachment styles (anxious and avoidant) have been associated with poor relationship quality, psychological vulnerability and maladjustment, and mental health difficulties (e.g. Sroufe et al., 1999; Hankin et al., 2005; Mikulincer & Shaver 2007; Groh 2016; Spruit 2019). However, the direction of causality is less well established as most studies rely on cross-sectional design and measure attachment style as a discrete variable at a single point in adulthood.
By using a large prospective birth cohort, we will be able to (a) investigate the prospective relationship and (b) use latent variable modelling of repeated measures of attachment to create a more robust and detailed measure of attachment style. This will aid more nuanced explanations of how and when insecure attachment style may lead to mental ill health, such that the association can be interrogated to identify possible intervention targets.
This proposal has implications for healthcare provision and public health policies around childhood and parental interventions to support research to address the growing number of mental health difficulties in later adolescence.
B3573 - The impact of loneliness in your adults - 20/07/2020
Recent data show young adults (age 16-30) experiencing extreme loneliness. Loneliness has a detrimental impact on health and wellbeing, however existing studies largely focus on older adults, meaning the full impact in young adults is unclear. Of particular concern is the likely adoption of negative health behaviours (including addictions), the harmful overuse or underuse of NHS services, and potential for self-harm or suicide in young adults experiencing loneliness. Also, of concern is the negative impact on milestones such as finishing school, further education and getting a first job, which contribute to household wealth and wellbeing. This research aims at using the ALSPAC data to assess the impact and cost of young adult loneliness in the UK with respect to health status, over or under use of health care resources, education attainment and unemployment. Regression analysis will identify correlations between variables, while causal relationships will be investigated through instrumental variable analysis and propensity score matching. Results will be used to update existing costs estimates that have focused only on older adults. Analysis will be conducted on data before, during and after COVID-19 to consider the prevalence and impact of young adult loneliness through COVID-19, given the likely exacerbation of loneliness in the context of social distancing. This research will develop understanding and inspire greater consideration of loneliness in young adults promoting cross-sector involvement and improved support.
B3571 - Genomic determinants of Multiple Sclerosis susceptibility in an ethnically diverse population - 19/08/2020
Multiple Sclerosis (MS) is a disorder of the brain and spinal cord which affects about 1 in 1000 people worldwide. In people with MS (pwMS), the immune system attacks the lining of nerve (myelin), leading to âattacksâ of disability which can last days-months, and a gradual accumulation of disability over time. Although there are many effective treatments for MS, there is still no cure. MS was previously thought to mainly affect White people, but recent evidence suggests this is untrue: in the USA, the number of newly-diagnosed people with MS is now higher among African American individuals than individuals of White European ancestry.
Most of our understanding of what causes MS comes from studies of European individuals. The largest genetic association study to date revealed over 200 sites in the genome associated with MS, but it remains unclear whether these insights - from an exclusively European cohort - apply to individuals from different ethnic backgrounds.
In this study, we attempt to perform the largest genetic association study of MS among Black, Asian, and Minority Ethnic (BAME) individuals to date in the UK. We will collect genetic data from people with MS and healthy controls from BAME backgrounds, and we will systematically search for genetic variants more common in the pwMS. We anticipate that this research will advance our understanding of what causes MS in BAME individuals, and may have important implications for our understanding of the causes of MS more broadly.
B3570 - Role of inflammation and psychosocial variables in the associations between prenatal maternal stress and offspring mental health - 14/07/2020
Risk towards poor mental health is impacted by a number of biological, psychological, and social factors that work together throughout the lifespan and across generations. A large body of research supports the influence of the prenatal environment on childrenâs developmental and mental health outcomes. For example, prenatal depression has been linked to later risk of depression in children, and prenatal depression, prenatal anxiety, and stressful life events during pregnancy have all been associated with risk of anxiety disorders in children. There is also growing interest in understanding the potential biological causes that may drive these relationships. In particular, inflammation has been suggested as a potential factor that may influence these associations, due to its role in the onset of depression and other mental and physical health disorders. However, few studies to date have examined the role of inflammation in relationships between prenatal maternal stress and child and adolescent mental health outcomes, calling for continued research in this area.
In addition, although the relationships between prenatal stress and child and adolescent mental health outcomes are well-established, children continue to be exposed to a number of influences, both positive and negative, after birth. For example, research suggests that the relationships between prenatal stress and child outcomes may differ depending on how mothers are able to cope with the stress they experience, including their degree of partner and social support, and availability of psychological resources including higher self-esteem and self-efficacy. Furthermore, a growing number of studies suggest that parenting behaviours may play an important role in these associations. For example, children exposed to parental warmth and positive relationships with their mothers and fathers may be buffered to the impacts of early adversity; conversely, children exposed to maltreatment or harsh parenting may exhibit increased vulnerability. Considering how both maternal coping resources and parenting further increase or reduce the risk towards chronic inflammation and later mental health outcomes in children exposed to prenatal stress, however, is an area that requires further investigation. In addition, the influence of many coping resources and parenting behaviours on later inflammation is an understudied area.
B3568 - The genetics of speech sound disorder - 13/07/2020
There is variation in when and how children develop speech in early childhood. Some children experience difficulties in the process but many of these have speech which is well developed by the time they start school. Some children have persistent problems which continue into early childhood. These problems can be associated with problems with educational attainment in older childhood as well as having difficulties in making themselves understood. Some of these children will have problems with their speech as a result of subtle problems with the coordination of the movements required for speech while others will have difficulties associated with the cognitive skills involved in developing speech. Some will have problems with both.
Genes have been identified which are associated with some types of speech and language difficulties but it is not yet clear what part genes may play in persistent speech sound disorder. The analysis outlined in this proposal will enable us to determine to what extent children's problems with speech after they have started school may be associated with genetic factors rather than environmental factors. This information will help us identify how best to help children who present with these difficulties to speech and language therapists and in school.
B3569 - Do asthma and ADHD have shared developmental origins - 13/07/2020
Children with asthma are more likely to suffer from attention deficit hyperactivity disorder (ADHD), but we do not understand why; it may be because the two conditions are influenced by similar risk factors early in life or by similar genes which affect lung and brain development. We will investigate this in ALSPAC. Gaining a better understanding of the causes of these common childhood conditions could ultimately lead to ways to prevent them.
B3567 - The intergenerational continuity of intimate partner violence an exploration of possible mechanisms - 07/07/2020
Intimate partner violence (IPV) is closely associated with the more commonly used term âdomestic violenceâ but is often considered to include a wider range of contexts and behaviours specifically with regard to partners in dating, cohabiting and marital relationships. IPV can be conceptualised as a continuum of abuse, including homicide, minor and severe physical assault, sexual assault, psychological abuse, including threats, harassment, coercion and intimidation. Various studies have demonstrated that both men and women can act as perpetrators and victims. IPV is increasingly reported and is thus a huge burden for public health as it occurs regardless of age, socio-economic status, gender and sexuality and it can result in a number of negative outcomes. These can include but are not limited to substance misuse, post-traumatic stress disorder, depression and suicidal ideation. Not least, and perhaps of greatest concern, is the possibility of intergenerational transmission of IPV. The relationships, particularly those between parents and children, are highly influential and life course events, drug and alcohol abuse and IPV can have a huge impact on their lives. This intergenerational transmission is a widely studied explanation of how family characteristics can impact on the development of aggression and violence in adult relationships. Children raised in households where they are exposed to acts of violence may in turn learn that violence is an appropriate reaction in interpersonal conflictual situations and act accordingly in their own relationships in adulthood. There is currently robust evidence to support this proposition, but there are inconsistencies. Children may have differential responses to this experience, and this may be explained by whether a child experiences abuse directly or only witnesses parental violence. There is currently a dearth of studies that use multiple waves of data garnered from prospective longitudinal studies that address the limitations of prior research. These limitations are the use of cross-sectional or short-term follow-ups, male only studies, female only studies and measurement anomalies. Further exploration of the intergenerational transmission of IPV is therefore warranted taking into consideration the limitations of prior research. A birth cohort provides ideal data to investigate this alongside the possibility of developing further knowledge of the underlying mechanisms involved. There are a number of factors that are known to increase the vulnerabilities for being involved as either victims or perpetrators of IPV. Some psychosocial factors such as family breakdown, maltreatment, mental and physical health, drug and alcohol abuse, personality traits and socio-economic disadvantage have all been shown to be associated with individual variations in IPV. Whether there is a direct relationship between any one of these factors and IPV is unclear, and it is likely that these factors and others may have interactive or sequential effects.
B3566 - Serological testing for COVID-19 in ALPSAC G0/G1 - 12/07/2020
The work is an effort to collect serological data on past infection status within the population based cohorts of the UK â in particular a set of cohorts which have been selected to report on 4 important axes of variation â ethnicity, age, socio-economic status and geography. The key thing for us is that we are able to move swiftly to capture the signature of infection and that we are able to exercise the cohorts (and all they bring re. retrospective data and new sample and data collection capacity) whilst being complementary to the efforts of existing studies â importantly REACT 2 and UKBB. We have been focusing on LFT and talking to those testing and developing kits. We have been pursuing the Orient gene kit as a strong option here â given performance, testing and our aim to use this as an epidemiological tool rather than an individually relevant test solution. Paul Elliott has been extremely generous with time and details re. the REACT 2 study and we are now proceeding with Orient gene as a viable option (home-based lateral flow antibody testing). We have been able to work with Peter Diggle (Lancaster) to develop the structure of our sampling frame across the 6 cohorts and now are primed to get approval locally (a process already started re. the PPI around these tests) in order to deliver kits to participants.
B3565 - Exome sequencing of ALSPAC children and parents - 14/07/2020
We wish to sequence the genes of ~7,000 ALSPAC children and parents for ~2,000 of them. We will use these data to identify rare genetic variants, combine these with existing data on common genetic variants, and then investigate the effects of these variants on the cognitive and behavioural development of ALSPAC children.
The rationale for this project comes from previous work which has shown that rare genetic variants in some genes affect children's risk of severe neurodevelopmental disorders (e.g. intellectual disability, autism), but these variants are often inherited from parents who appear to have normal cognitive functioning. We have shown that, on average, these variants affect the normal spectrum of cognition in adults, as well as mental health traits and reproductive success. We suspect that the effect of these rare genetic variants might be modified by other more common variants in individualsâ genomes, which have also been shown to affect cognitive ability, as well as environmental factors. Furthermore, these effects may change across a personâs lifetime, and may be modified by the parentsâ behaviour and genes.
We wish to use the rich longitudinal data on cognitive development, behaviour and educational achievement of ALSPAC children at different ages to investigate the joint impact of rare and common genetic variants on cognitive development, and whether these are modified by the parentsâ behaviour. We will also look at genetic effects on mental health, as well as behavioural and personality traits relevant to reproductive success.
B3564 - Implications of covid-19 lockdown for inequalities in health - 01/07/2020
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 âlockdownâ changed peopleâs behaviour radically, but the socioeconomic differences in these experiences are not well understood. Some groups of society may have increased health-promoting behaviours â 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 â 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 â 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.
B3562 - Exploring self-harm and disordered eating as risk factors for poorer mental health during the COVID-19 pandemic - 30/06/2020
Individuals with either disordered eating or self-harm are already at increased risk of mortality and psychiatric comorbidity, and this is likely exacerbated by the pandemic.
During COVID-19, young adults with disordered eating or self-harm are at increased risk of mental health problems (https://www.medrxiv.org/content/10.1101/2020.06.16.20133116v1).
However, little is known about whether specific sub-groups (e.g. binge-eating, suicide attempt) are at particular risk, and what factors could mitigate this risk. Investigation using high-quality data sources is vital to help develop targeted interventions and inform policy for these vulnerable groups.
This study examines whether individuals with different types of disordered eating (fasting, binge-eating, purging, excessive exercise) and self-harm (non-suicidal self-injury, suicide attempt) are at particular risk of poorer mental health (depression, anxiety, mental wellbeing) during the COVID-19 pandemic. Furthermore, this study examines what mitigating factors (e.g. social interactions, visiting green space) may help with COVID-related mental health problems in those with different types of disordered eating and self-harm.
B3563 - The effectiveness of public health advice about healthy eating on dietary change and associations with cardiovascular profiles i - 30/06/2020
Public health messages about what constitutes a healthy diet have been promoted by the UK government since the early 1990s. These messages have been based on developing knowledge about foods and eating patterns that result in better health. The ways in which these messages actually influence the diet of the population and the effect on the risk of diseases such as heart disease have not been studied over the long-term. We plan to use data on diet collected from mothers in ALSPAC to see how their diet changes over time in parallel with changes in public messages about nutrition, and whether any changes have reduced their risk of heart disease. This will help policymakers to develop guidance for maximum impact on women's health.