Proposal summaries
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.
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.
B3557 - Exploring shared genetic associations between risk behaviours and educational attainment - 07/07/2020
People who participate in risky behaviours such as drug use, physical inactivity and criminal behaviour have lower educational attainment than people who abstain from such behaviour. The effects of participating in risky behaviours have been estimated at around a one grade reduction at GCSE or 23% lower odds at attaining five of more A*-C GCSE grades, for each additional behaviour the young person engages in. This can have a detrimental knock on effect on subsequent education and employment chances in later life causing lasting socioeconomic damage. Genome Wide Association Studies have revealed that participation in risky behaviours and educational attainment both have highly polygenic architecture, suggesting an important role of many variants across the genome. The extent to which risky behaviours and educational attainment have shared genetic overlap is unknown, yet knowledge of this could help understand how these traits co-operate.
B3558 - Investigating Resilience Mechanisms in Neurodevelopmental Conditions - 01/07/2020
Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are neurodevelopmental conditions affecting ~10% of people. Young people with ASD and ADHD experience substantial adversity (e.g. bullying, maltreatment) which is linked with poor adult outcomes. However, some people may show resilience, demonstrating adaptive outcomes, for example positive wellbeing, despite this adversity.
I will explore resilience in ASD and ADHD, from childhood to young adulthood. I will conduct a qualitative study to determine what adaptive outcomes look like to young people with ASD/ADHD. Then, using data from two large studies that follow young people over time, I will investigate factors linked with adaptive outcomes in ASD and ADHD. Using innovative statistical analyses, I will test the roles of child characteristics, the family and social environment, and genetics.
The findings will inform future interventions to reduce adversity and boost resilience amongst young people with neurodevelopmental conditions.
B3482 - Factors associated with third molar pathology and treatment in a representative population - 30/06/2020
Changes in dental practice as a result of NICE âGuidance on the Extraction of Wisdom Teethâ, mean that fewer adults now have prophylactic removal of their wisdom teeth. However, recent studies have demonstrated an increase in the risk of infection, dental decay and gum disease in angled wisdom teeth or in the neighbouring teeth since the implementation of NICE guidance.
This means we are seeing an increasing number of patients who may present with disease affecting wisdom teeth or the neighbouring teeth, so there is a need therefore to identify those who are at risk of developing wisdom tooth complications and who may benefit from removal. In addition, we will better our understanding of the potential barriers to receiving appropriate wisdom tooth treatment.
B3556 - Associations between physical activity risk of alcohol-related harm in adolescence cross-sectional and longitudinal analysis - 23/06/2020
Adolescence is a critical stage of life for the formation of both physical and mental health. Health behaviours and health status developed in adolescence often endure into adulthood and influence life expectancy. Health-risk behaviours such as excessive alcohol consumption and physical inactivity are not only linked with mental health, but are also two major contributors (globally) to disease in adulthood such as cancer, diabetes and cardiovascular disease. Adolescence is a time when physical activity levels decline, alcohol consumption increases and mental health states can deteriorate. However, conversely, research shows links between higher physical activity levels and higher levels of alcohol consumption (although largely this has been derived from non UK-based University/College populations). Advice given by a former UK Chief Medical Officer is that children should not drink at all before the age of 18 but certainly not before the age of 15. Excessive alcohol consumption can result in unwanted consequences (particularly in adolescence) such as being a perpetrator or victim of violence or other criminal activity, or unprotected (or regretted) sexual activity. Alcohol has been strongly linked to suicide in adolescence (the number one cause of preventable death); as well as more generally impacting or impeding healthy brain development. Other factors (which contribute to or cause inequalities in health outcomes) also should be considered when looking at health behaviours in adolescence e.g. socioeconomic status (SES), educational attainment, gender and psychosocial health. Those with a lower SES (SES - being typically derived from household income and education levels) tend to fare worse in health outcomes. Despite higher levels of physical activity being associated with higher SES in adolescence (as is a higher level of alcohol consumption), it appears that higher educational attainment (also correlated with higher SES) reduces the occurrence or frequency of binge-drinking. While those from lower SES backgrounds are more likely to experience greater harms from alcohol consumption. Gender contributes significantly to health inequalities, disadvantaging girls. In early adolescence, girls are more likely to be diagnosed with an anxiety or depressive disorder, more likely to have lower levels of physical activity and are more likely to be at risk of alcohol-related harm than their male equivalents. Mental health is becoming one of the biggest issues we face globally and has been strongly linked to physical activity/inactivity. Those that undertake regular physical activity are less likely to be depressed, but conversely are more likely to consume alcohol at higher levels (and in particular binge-drink). This research will seek to untangle the links between risk of alcohol-related harm and levels of physical activity at ages 13.5, 15.5 and 17.5 using data in the âChildren of the 90âs cohortâ from the Avon Longitudinal Study of Parents and Children (ALSPAC). The research will determine associations or patterns at each time-point (age in years) and also make comparisons of changes over time. The individual-level analysis (longitudinal) will also utilise data for 24.5 year olds to compare with 17.5 year olds The following factors will be used as a means of explaining findings at each time-point, individually, and collectively: SES, educational attainment, gender and psychosocial health. The aim is to create new knowledge on the associations and patterns between physical activity and alcohol consumption levels across early to late adolescence in a UK population. Findings will inform further UK-based research on this topic.
B3542 - Sensory Sensitivity Misophonia Hyperacusis and Tinnitus - 10/06/2020
Most people have a comfortable tolerance for incoming sensory information (sounds, tastes, smells etc.) while others have sensory sensitivities which can make daily life difficult. One example is sensitivity to sounds, and there are several ways this can present. For people with MISOPHONIA, certain sounds such as chewing cause an extreme emotional response such as anger, disgust or anxiety; and for people with HYPERACUSIS, loud sounds cause the ears to physically hurt. Sensory sensitivity can have a negative impact on mental well-being, and also plays a role in a number of conditions including autism spectrum conditions, anxiety disorders, and synaesthesia. In turn, poor well-being can have significant financial costs with over £12 billion invested annually by the NHS. Our study has become all the more relevant given the COVID crisis because we are interested in a condition that triggers anxiety/anger/distress, and has particular resonance for family relationships in confined spaces.
These sound sensitivities are poorly understood in adults, and even less so in children. In our project we ask, how do sound sensitivities such as misophonia affect mental well-being, education and attainment? Does misophonia get progressively worse over time? What other mental heath conditions commonly co-occur with misophonia? In answering these questions we can better understand the underlying aetiologies, which in turn will allow us to develop targeted treatments for misophonia.
B3550 - Long-term outcomes of antidepressant use a machine learning approach - 01/06/2020
This project aims to understand the long-term effects of antidepressant use in the adult population.
There is currently a gap in the literature regarding the longitudinal effects of pharmaceutical
interventions for depression, so there is not great clinical understanding of the impact of
antidepressants on health outcomes long-term. For example, some longitudinal studies suggest that
the symptoms of depression improve overall after long term antidepressant use, but this is reported
in tandem with adverse psychological and physical health outcomes like weight gain, sexual
dysfunction, and emotional numbness (Dehar et al. 2016). In the psychiatric literature, there is an
impoverished understanding of depression causality, with multiple competing hypotheses
suggesting genetic, psychological, neurochemical, and neurostructural correlates of the illness. This
suggests that depression as an overarching umbrella term could include multiple phenotypes, that if
captured, could explain different illness trajectories and predict differential health outcomes after
pharmaceutical intervention.
The long-term effects of antidepressant use on a wide range of health outcomes should be explored
to ascertain whether they are an optimal intervention for people who present with mild to
moderate depression and anxiety.
B3552 - Methods of recruitment and retention of fathers in cohort and longitudinal studies - 05/06/2020
In research projects focussed on children and families, information about children is often gathered via a single parent, often the child's mother or female caregiver. For many such studies, there are valid scientific reasons why involvement of the child's father or male caregiver is also important. For cohort studies, which follow families over time, early recruitment and ongoing engagement of fathers can be particularly important. However, recruiting and engaging fathers to such studies can be challenging, especially if fathers and mothers do not live together. As a result fathers are widely under-represented in such research. A scoping review of recruitment and engagement methods suggests that involving fathers may require a different approach to that used for mothers. This study seeks to review how fathers are recruited and engaged in the ALSPAC G2 cohort, to propose tailored recommendations to improve recruitment and engagement and test the feasibility and acceptability of the revised, tailored approach with participants and research staff. The general learning from this process is expected to be relevant to many similar research projects.
B3551 - Risky Business Understanding intergenerational persistence in entrepreneurship - 05/06/2020
Entrepreneurship is with good reason viewed as a driver of economic growth, employment creation, and social mobility: in 2018, there were 5.7 million small-medium enterprises in the UK, accounting for 99.9% of all businesses, 60% of employment and 52% of the gross value added in the UK private sector. Of these, 96% were micro-businesses with less than 10 employees (Business Statistics, Standard Note, SN/EP/6152, House of Commons Library, December 2018). In fact, policymakers advocate support to entrepreneurship as a way forward for socioeconomic development at regional and national level, therefore helping these firms to form is key to UK prosperity. Government support for entrepreneurs often takes a macro perspective of intervention through subsidies and infrastructure. There is, however, increasing recognition in the entrepreneurship field that the decision to become an entrepreneur and start new ventures is strongly embedded in the close and personal space surrounding an individual, starting from their family relationships. It is well known that self-employment and business ownership choices are highly persistent across generations: entrepreneurial parents tend to have entrepreneurial children. We know much less, however, about the underlying mechanisms that transmit and shape those choices. This is what our project will address. We will examine the ways in which entrepreneurial parents affect their childrenâs entrepreneurial preferences and behaviours directly â through being role models and providing advice â and indirectly â through shaping attitudes to risk and uncertainty, and exposing the stresses and wellbeing impacts inherent in starting a business. Our findings will identify new ways in which policy can encourage and nurture entrepreneurialism.
B3549 - EWAS of Green Spaces - LifeCycle - 24/06/2020
The urban exposome (built environment, air pollution, road traffic noise, meteorological, natural space and road traffic) affects health outcomes. For instance, associations between increasing green space exposure and increased birth weight and decreased term low birth weight in 32,000 mother-child pairs have been previously reported (Nieuwenhuijsen et al. 2019).
Here we aim to investigate the epigenetic mechanisms that might mediate this association. We will evaluate the relationship between exposure to green spaces during pregnancy and offspring cord blood DNA methylation at over 450,000 methylation sites (CpG sites) across the genome. This project will contribute epigenome-wide association study summary results to a meta-analysis as part of an ongoing large consortium.
B3548 - Investigating the influence of natural selection on metabolites - 28/05/2020
Environmental and genetic factors both play a role in shaping individual variation. Characteristics that increase an individualâs chance of survival and reproduction are more likely to be passed onto the next generation. This process is known as natural selection and it is reflected at the genetic level. Negative selection is a form of natural selection whereby rare genetic factors with harmful effect on survival and reproduction are removed from populations. Recent studies have found evidence of negative selection acting on complex traits such as body mass index (BMI), blood pressure and height.
This project will explore how natural selection influences molecular traits. Metabolites are intermediates or end products of biological processes and they are linked to numerous diseases. Gaining a better understanding of how metabolites are related to survival and reproduction will enable researchers to prioritise specific research avenues. This prioritisation may improve human health.
B3547 - A UK underpinning platform to study immunology and immunopathology of COVID-19 The UK Coronavirus Immunology Consortium - 03/06/2020
B3546 - UKRI Future Leaders Fellowship The heart-brain connection in ALSPAC30 cardioaggression and neuroselection - 02/06/2020
As more people live to old age, dementia is on the rise, but there is currently no effective treatment. This comes at enormous personal, societal and economic cost. I and others have previously shown that a decrease in heart function is associated with early cognitive impairment, however the underlying cause is not clear. It is possible that poor heart function may lead to poor blood flow in the brain, which may be the link. Another possible link between the heart and the brain runs in the opposite direction. Instead of heart problems leading to brain problems, it could be that lower cognitive function as a child leads to heart problems later in life. I will investigate the direction of the heart-brain association in 30yr olds from the ALSPAC cohort, that have had data collected since birth, including genetic, cognitive and heart measures. I will collect new detailed data on the heart and the brain during rest and during exercise. The results of this study are important as dementia is a public health priority. The clinical implications of reduced cognition among people with impaired heart function are considerable. By understanding the underlying mechanisms, we can reduce the burden of both of these conditions.
B3545 - School starting age the role of gene-environment interactions - 03/06/2020
It is well known that September-born children perform better on school tests than August-borns, most likely because they are "older in the year". This project aims to explore the importance of gene-environment interplay within this context. More specifically, it will investigate whether this September-effect, or the effect of being "old in the academic year", varies with an individual's genetic predisposition, as proxied by a polygenic score for cognitive ability, for educational attainment, and for 'non-cognitive' skills. We will examine the effects on cognitive outcomes such as academic achievement, as well as on non-cognitive skills, such as the children's "strength and difficulties".