Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B3568 - The genetics of speech sound disorder - 13/07/2020

B number: 
B3568
Principal applicant name: 
Yvonne E Wren | University of Bristol (UK)
Co-applicants: 
Professor Angela Morgan, Dr Dianne Newbury
Title of project: 
The genetics of speech sound disorder
Proposal summary: 

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.

Impact of research: 
An understanding of the genetic basis for persistent speech sound disorder
Date proposal received: 
Thursday, 9 July, 2020
Date proposal approved: 
Monday, 13 July, 2020
Keywords: 
Genetics, Speech/language problem, Gene mapping, Speech and language

B3567 - The intergenerational continuity of intimate partner violence an exploration of possible mechanisms - 07/07/2020

B number: 
B3567
Principal applicant name: 
Delphine Theobald | Kingston University (UK)
Co-applicants: 
Dr Sania Shakoor, Professor David P. Farrington
Title of project: 
The intergenerational continuity of intimate partner violence: an exploration of possible mechanisms
Proposal summary: 

Intimate partner violence (IPV) is closely associated with the more commonly used term ‘domestic violence’ 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.

Impact of research: 
This project will provide deeper aetiological knowledge and provide an insight into the behavioural profiles of those exposed to intimate partner violence (IPV). It will be of interest to academics as it will add to knowledge with regard to the continuity of IPV from one generation to the next and explore possible underlying pathways. It will be of relevance to public health practitioners and policy makers as IPV is robustly associated with negative health outcomes . Furthermore, through the identification of mediators, findings from this project could be used to inform interventions aimed at supporting and reducing the impact of IPV.
Date proposal received: 
Tuesday, 7 July, 2020
Date proposal approved: 
Tuesday, 7 July, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Social science

B3566 - Serological testing for COVID-19 in ALPSAC G0/G1 - 12/07/2020

B number: 
B3566
Principal applicant name: 
Nicholas Timpson | University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
Serological testing for COVID-19 in ALPSAC (G0/G1)
Proposal summary: 

The work is an effort to collect serological data on past infection status within the population based cohorts of the UK – in particular a set of cohorts which have been selected to report on 4 important axes of variation – 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 – 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 – 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.

Impact of research: 
This work has the chance to assess antibody response VS infection rate VS clinical presentation in Bristol with a home-based test able also to compare patters in Bristol to those in other (demographically different) cities/areas. Careful interpretation of the data will be required, however this work does have the chance to inform understanding of infection, prevalence, age differences, socio-demographic gradients, life course contributions to outcomes and susceptibility and the utility of this form of testing.
Date proposal received: 
Monday, 6 July, 2020
Date proposal approved: 
Monday, 6 July, 2020
Keywords: 
Immunology, Infection, serological testing, COVID-19, Infection, serology

B3565 - Exome sequencing of ALSPAC children and parents - 14/07/2020

B number: 
B3565
Principal applicant name: 
Hilary Martin | Wellcome Sanger Institute
Co-applicants: 
Prof Matthew Hurles
Title of project: 
Exome sequencing of ALSPAC children and parents
Proposal summary: 

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 individuals’ genomes, which have also been shown to affect cognitive ability, as well as environmental factors. Furthermore, these effects may change across a person’s lifetime, and may be modified by the parents’ 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 parents’ behaviour. We will also look at genetic effects on mental health, as well as behavioural and personality traits relevant to reproductive success.

Impact of research: 
Our research will lead to a greater understanding of how different types of genetic factors affect cognitive development, and the extent to which these are modified by parental phenotypes. This may help to understand the conundrum of incomplete penetrance in the context of neurodevelopmental disorders and ultimately may lead to improvements in genetic counselling for these disorders. Furthermore, our research will increase our understanding of the mechanisms by which rare, damaging genetic variants affect fertility, and hence the nature of negative selection acting on these variants.
Date proposal received: 
Thursday, 2 July, 2020
Date proposal approved: 
Thursday, 2 July, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Fertility/infertility, Learning difficulty, Mental health, Speech/language problem, DNA sequencing, GWAS, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Sex differences, Speech and language

B3564 - Implications of covid-19 lockdown for inequalities in health - 01/07/2020

B number: 
B3564
Principal applicant name: 
Laura Howe | MRC IEU (United Kingdom)
Co-applicants: 
Amanda Hughes, Kate Northstone, Beki Langford
Title of project: 
Implications of covid-19 lockdown for inequalities in health
Proposal summary: 

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.

Impact of research: 
will hopefully feed into local and potentially national efforts to address inequalities resulting from covid
Date proposal received: 
Tuesday, 30 June, 2020
Date proposal approved: 
Wednesday, 1 July, 2020
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Obesity, Social science

B3562 - Exploring self-harm and disordered eating as risk factors for poorer mental health during the COVID-19 pandemic - 30/06/2020

B number: 
B3562
Principal applicant name: 
Naomi Warne | Population Health Sciences, Bristol Medical School, University of Bristol (England, UK)
Co-applicants: 
Dr Helen Bould, Dr Jon Heron, Dr Becky Mars, Dr Francesca Solmi, Professor Paul Moran
Title of project: 
Exploring self-harm and disordered eating as risk factors for poorer mental health during the COVID-19 pandemic
Proposal summary: 

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.

Impact of research: 
This project will lead to a greater understanding of the mental health of young adults with disordered eating and self-harm during the COVID-19 pandemic. We hope to identify factors that could help reduce pandemic-related mental health problems in these vulnerable groups.
Date proposal received: 
Sunday, 28 June, 2020
Date proposal approved: 
Tuesday, 30 June, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Eating disorders - anorexia, bulimia, Mental health, COVID-19, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Epidemiology

B3563 - The effectiveness of public health advice about healthy eating on dietary change and associations with cardiovascular profiles i - 30/06/2020

B number: 
B3563
Principal applicant name: 
Caroline Taylor | Dr (United Kingdom)
Co-applicants: 
Dr Pauline Emmett, Dr Genevieve Buckland
Title of project: 
The effectiveness of public health advice about healthy eating on dietary change and associations with cardiovascular profiles i
Proposal summary: 

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.

Impact of research: 
The unique longitudinal data available in ALSPAC will be used to assess changes in diet at a time when the possible impact of diet on long-term health had been widely publicised to the general public. The results will allow us to assess whether general publicity about ‘healthy’ diet leads to any meaningful change in dietary habits and whether this has any long-term effect on CVD risk. We will also be able to assess whether the use of dietary index scores is able to detect meaningful dietary change and which of the four scores tested are most able to predict a heart healthy diet in English women. If the impact of general advice is demonstrated to have improved eating habits and improved CVD risk this will encourage further general publicity. However, if no effect on diet or CVD risk is detected it will indicate that more finely targeted measures to improve diet should be developed.
Date proposal received: 
Tuesday, 30 June, 2020
Date proposal approved: 
Tuesday, 30 June, 2020
Keywords: 
Epidemiology, Nutrition Cardiovascular disease, Statistical methods, Nutrition - breast feeding, diet

B3557 - Exploring shared genetic associations between risk behaviours and educational attainment - 07/07/2020

B number: 
B3557
Principal applicant name: 
Tim Morris | MRC Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Dr Caroline Wright, Miss Michelle Arellano Spano
Title of project: 
Exploring shared genetic associations between risk behaviours and educational attainment.
Proposal summary: 

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.

Impact of research: 
This research
Date proposal received: 
Tuesday, 23 June, 2020
Date proposal approved: 
Tuesday, 23 June, 2020
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, Genetics

B3558 - Investigating Resilience Mechanisms in Neurodevelopmental Conditions - 01/07/2020

B number: 
B3558
Principal applicant name: 
Lucy Anne Livingston | Cardiff University (United Kingdom)
Co-applicants: 
Professor Anita Thapar, Professor Francesca Happé, Professor Stephan Collishaw, Dr Jon Heron, Dr Meng-Chuan Lai
Title of project: 
Investigating Resilience Mechanisms in Neurodevelopmental Conditions
Proposal summary: 

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.

Impact of research: 
Studying resilience has potential to improve clinical and educational support, and thereby outcomes, for people with neurodevelopmental conditions; for example, interventions that aim to boost resilience amongst young people with neurodevelopmental conditions.
Date proposal received: 
Monday, 15 June, 2020
Date proposal approved: 
Tuesday, 16 June, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Developmental disorders - autism, Statistical methods, Development

B3482 - Factors associated with third molar pathology and treatment in a representative population - 30/06/2020

B number: 
B3482
Principal applicant name: 
Rebecca Richmond | University of Bristol (United Kingdom)
Co-applicants: 
Dr Tom Dudding, Dr Simon Haworth, Douglas Bruce, Mark Gormley
Title of project: 
Factors associated with third molar pathology and treatment in a representative population
Proposal summary: 

Changes in dental practice as a result of NICE “Guidance on the Extraction of Wisdom Teeth”, 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.

Impact of research: 
The results from this study will be used to help identify those patients who are at risk of third molar (wisdom tooth) related pathology and who require prophylactic removal. As part of this we will establish the importance of host genetic factors in third molar symptoms. Prediction of third molar pathology could be very cost-effective, identifying those most in need in order to prevent the cost of managing future problems i.e. periodontitis (gum disease), dental caries (decay), infection and even sepsis. There may be similar associations with risk factors for third molar pathology and other dental diseases which would enhance the applicability of this risk prediction model.
Date proposal received: 
Friday, 12 June, 2020
Date proposal approved: 
Monday, 15 June, 2020
Keywords: 
Dentistry, Third molar (dental) pain/ infection/ treatment., Statistical methods, Dental

B3556 - Associations between physical activity risk of alcohol-related harm in adolescence cross-sectional and longitudinal analysis - 23/06/2020

B number: 
B3556
Principal applicant name: 
Lesley Smith | University of Hull (United Kingdom)
Co-applicants: 
Ms Saphsa Codling, Professor Thomas S Phillips, Professor Colin R Martin
Title of project: 
Associations between physical activity, risk of alcohol-related harm in adolescence: cross-sectional and longitudinal analysis
Proposal summary: 

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 ‘Children of the 90’s cohort’ 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.

Impact of research: 
Currently there is an absence of evidence in UK adolescents on the association between physical activity levels and alcohol consumption (particularly in early adolescence). This research will not only contribute to empirical evidence in this area but will also help to identify a population (or populations) that could benefit from early preventative measures to delay or prevent the onset of alcohol consumption during the critical early adolescence period.
Date proposal received: 
Wednesday, 10 June, 2020
Date proposal approved: 
Wednesday, 10 June, 2020
Keywords: 
Biostatistics, behavioural science and prevention, Alcohol related harm Health risk behaviour Mental health, Statistical methods, Health risk behaviours Adolescent mental health Physical activity Alcohol consumption

B3542 - Sensory Sensitivity Misophonia Hyperacusis and Tinnitus - 10/06/2020

B number: 
B3542
Principal applicant name: 
Julia Simner | University of Sussex (United Kingdom)
Co-applicants: 
Dr Louisa Rinaldi, Prof. Jamie Ward, Dr James Alvarez, Ms Rebecca Smees
Title of project: 
Sensory Sensitivity: Misophonia, Hyperacusis and Tinnitus
Proposal summary: 

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.

Impact of research: 
The impact of our research will be considerable, both in the field of auditory sensitivities, but also sensory sensitivities more widely, as well as in related conditions (autism) and more broadly in the field of education. Misophonia was first identified as recently as 2001 (Jastreboff & Jastreboff, 2001). As a new area of research, there is still much to learn. We will come to understand how/when misophonia initially presents, how it impacts school life, education, mental health, and overall well-being. Our findings will have important implications for developing targeted diagnostics and treatments for childhood populations. We will better understand schooling (Do children with misophonia have poorer attendance? Lower attainment? Difficulties paying attention in class?). And we will also better understand the prevalence of these conditions. We will then use our findings to raise awareness of the conditions, to inform parents and educators, and ultimately improve the lives of both children and adults with misohponia/hyperacusis.
Date proposal received: 
Tuesday, 9 June, 2020
Date proposal approved: 
Tuesday, 9 June, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Eating disorders - anorexia, bulimia, Learning difficulty, Mental health, sensory differences; sensory sensitivities, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Intelligence - memory, Mothers - maternal age, menopause, obstetrics, Parenting, Psychology - personality, sensory differences; sensory sensitivities

B3550 - Long-term outcomes of antidepressant use a machine learning approach - 01/06/2020

B number: 
B3550
Principal applicant name: 
Rebecca Pearson | Digital Health
Co-applicants: 
Holly Fraser , Bittany Davidson , Ryan Mcconville, Dr Alex Kwong
Title of project: 
Long-term outcomes of antidepressant use, a machine learning approach
Proposal summary: 

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.

Impact of research: 
To inform use of antidepressants in certain populations
Date proposal received: 
Monday, 1 June, 2020
Date proposal approved: 
Monday, 1 June, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Psychology - personality

B3552 - Methods of recruitment and retention of fathers in cohort and longitudinal studies - 05/06/2020

B number: 
B3552
Principal applicant name: 
Paul Bradshaw | Scottish Centre for Social Research (United Kingdom)
Co-applicants: 
Lynn Molloy, Line Knudsen, Rebecca Goldman, Adrienne Burgess
Title of project: 
Methods of recruitment and retention of fathers in cohort and longitudinal studies
Proposal summary: 

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.

Impact of research: 
As well as potentially offering a set of tailored recommendations which may improve the participation of fathers in ALSPAC G2, this research will also be relevant for other cohort studies and related projects which are seeking to better involve and engage fathers in research about their children. In particular, it may have a role in informing the design of any future UK national or other large cohort study.
Date proposal received: 
Monday, 1 June, 2020
Date proposal approved: 
Monday, 1 June, 2020
Keywords: 
Statistics/methodology, Methods for the recruitment and engagement of research participants, Cohort studies - attrition, bias, participant engagement, ethics, Fathers

B3551 - Risky Business Understanding intergenerational persistence in entrepreneurship - 05/06/2020

B number: 
B3551
Principal applicant name: 
Matt Dickson | University of Bath (UK)
Co-applicants: 
Prof. Orietta Marsili
Title of project: 
Risky Business: Understanding intergenerational persistence in entrepreneurship
Proposal summary: 

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 children’s entrepreneurial preferences and behaviours directly – through being role models and providing advice – and indirectly – 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.

Impact of research: 
Our project emphasises the dual relationship linking the family context and entrepreneurship. On one side, the family can facilitate the emergence of preferences for entrepreneurship in the children by providing the ‘learning space’ in which children observe how entrepreneurs live and operate through the experience of their entrepreneurial parents. On the other side, the family can be the ‘resounding space’ of the successes but also the frustrations of being an entrepreneur, which may lead to the development in the children of negative emotions in association with entrepreneurship. Understanding the complex role of the family in entrepreneurship is of interest for different constituencies, starting from the public and the entrepreneurial parents more specifically. Thanks to the internet, setting up a business from home has become a choice increasingly available to people, parents in particular. Indeed, the Government is committed to making the UK the best place to start and grow a business, with particular initiatives – such as the £1million Women and Broadband Challenge and the ASPIRE fund – aiming to encourage more women to set-up their own businesses. For mothers especially, the decision to become entrepreneur is often motivated by the prospect of achieving a better work-life balance. One of the expected outcomes of this project is to highlight the implications of being an entrepreneurial parent on the wellbeing of their children. Our findings can thus enhance awareness among parents of the implications of their employment choices not only from a business perspective but also more broadly in relation to the impact on the family lifestyle. This can lead to a better understanding of the challenges of achieving a work-life balance and can inform a broader discussion about how to meet and mitigate these challenges. This discussion involves not only entrepreneurial parents as direct subjects, but also policymakers who want to pursue a more holistic approach to entrepreneurship policy, in which the entrepreneur is regarded not only as a driver of change and wealth creation, but also as an individual embedded in a social context of personal relationships. In this type of policy approach, it is key to ask how to support children in families in which there is a risk that the uncertainties of entrepreneurship resonate too loudly. Given the policy relevance of this work for a number of areas, we will engage with the Department for Business, Energy and Industrial Strategy (BEIS) as a primary research user, and also with the Department for Work and Pensions as there are implications for the design of work-related benefits. Another implication of our argument is that entrepreneurship needs a supporting environment that goes beyond the provision of incentives and infrastructure, and which finds its root in the family. Illustrating how entrepreneurial parents can be positive role models that inspire younger generations, helping them to take on board the challenges of an entrepreneurial career, aids understanding of how to create a broader learning environment for entrepreneurship. Entrepreneurship education mostly takes place in dedicated programmes at universities, generally at Masters level and in Business Schools. Yet the family is the most immediate and personal environment in which children can learn about ‘the way of life of the entrepreneur’. Furthermore, while university entrepreneurship education tends to focus on the business principles underlying the creation of a new venture, a more broadly defined notion of entrepreneurship education involves enabling the development of creative mind-sets and the capacity to embrace uncertainty. Families and schools are likely terrain for this type of learning. From this perspective, our project can inform the discussion about the design and impact of practices for extending entrepreneurship education to children and young people. Indeed, a number of recent initiatives have been implemented in the last five years by the Government with the purpose of promoting entrepreneurship by engaging with young people early on through the education system. Our work will inform these initiatives, with parties involved in this discussion including formal and informal education providers (schools, parents, and charities) as well as government policy-related agencies and the Department for Education.
Date proposal received: 
Monday, 1 June, 2020
Date proposal approved: 
Monday, 1 June, 2020
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Hypertension, Mental health, Obesity, Statistical methods, Blood pressure, BMI, Childhood - childcare, childhood adversity, Cognition - cognitive function, Offspring, Psychology - personality, Social science, Statistical methods

B3549 - EWAS of Green Spaces - LifeCycle - 24/06/2020

B number: 
B3549
Principal applicant name: 
Kimberley Burrows | MRC IEU (United Kingdom)
Co-applicants: 
Dr. Ahmed Elhakeem, Prof. Debbie Lawlor, Mr Andy Boyd, Mr Richard Thomas
Title of project: 
EWAS of Green Spaces - LifeCycle
Proposal summary: 

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.

Impact of research: 
To contribute to the wider understanding of the effects of the urban exposome on health outcomes; specifically, in how DNA methylation may mediate these effects. Potential results may lead to significant new understanding and possibly have translatable benefits for improving human health. Such benefits would be to determine new pathways influencing disease that could be potential therapeutic targets.
Date proposal received: 
Friday, 29 May, 2020
Date proposal approved: 
Friday, 29 May, 2020
Keywords: 
Epidemiology, No direct analysis of diseases as such, we will be exploring the associations of the environment on DNA methylation. , Statistical methods, Birth outcomes, Environment - enviromental exposure, pollution, Epigenetics

B3548 - Investigating the influence of natural selection on metabolites - 28/05/2020

B number: 
B3548
Principal applicant name: 
Tom Gaunt | MRC IEU University of Bristol (United Kingdom )
Co-applicants: 
Charlie Hatcher , Dr Santi Rodriguez , Dr Josine Min , Dr Daniel Lawson
Title of project: 
Investigating the influence of natural selection on metabolites
Proposal summary: 

Environmental and genetic factors both play a role in shaping individual variation. Characteristics that increase an individual’s 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.

Impact of research: 
This work will investigate whether selection at the complex trait level is reflected at the molecular trait level (specifically metabolites), thus enabling us to better understand the relationship between complex traits, molecular traits and fitness. Understanding selection on molecular traits such as metabolites will ultimately help to identify biological pathways that can be intervened on to prevent and/or cure disease. Additionally, detecting regions of the genome under selection can also be used to help prioritise GWAS hits.
Date proposal received: 
Wednesday, 27 May, 2020
Date proposal approved: 
Thursday, 28 May, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Statistical methods, Genetic epidemiology

B3547 - A UK underpinning platform to study immunology and immunopathology of COVID-19 The UK Coronavirus Immunology Consortium - 03/06/2020

B number: 
B3547
Principal applicant name: 
Paul | Birmingham University
Co-applicants: 
Nicholas Timpson, Sue Ring, Adam Finn, Laura Rivino, Linda Wooldridge
Title of project: 
A UK underpinning platform to study immunology and immunopathology of COVID-19: The UK Coronavirus Immunology Consortium
Proposal summary: 
Impact of research: 
Understanding of COVID-19 immune response
Date proposal received: 
Wednesday, 27 May, 2020
Date proposal approved: 
Thursday, 28 May, 2020
Keywords: 
Immunology, Infection, Serological testing for COVID-19 (remote blood collection), detailed followup and immunology following blood collection. , Immunity

B3546 - UKRI Future Leaders Fellowship The heart-brain connection in ALSPAC30 cardioaggression and neuroselection - 02/06/2020

B number: 
B3546
Principal applicant name: 
Chloe Park | UCL (UK)
Co-applicants: 
Professor Alun Hughes, Professor Nish Chaturvedi
Title of project: 
UKRI Future Leaders Fellowship: The heart-brain connection in ALSPAC@30: cardioaggression and neuroselection?
Proposal summary: 

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.

Impact of research: 
Dementia is the greatest global health and social challenge in current times, there is no cure and its impact is devastating, but it does not have to be an inevitable consequence of aging. If we can understand the mechanisms then we can intervene and prevent/delay its effects. I propose that there is a bidirectional association between cognition and cardiovascular disease and by applying sophisticated methodologies and techniques to assess cardiac and brain function and haemodynamics, and by applying a life-course approach, this investigation will significantly advance our understanding of the causal mechanisms underlying both cardiac and cognitive decline. No previous study has assessed the heart-brain connection during dynamic testing in this age group or with a bi-directional, RbG approach before. The results could highlight the potential for early life intervention to preserve both cognitive function and cardiovascular health.
Date proposal received: 
Tuesday, 26 May, 2020
Date proposal approved: 
Wednesday, 27 May, 2020
Keywords: 
Physiology, Cognitive dysfunction and Cardiac dysfunction, Medical imaging, Cardiovascular

B3545 - School starting age the role of gene-environment interactions - 03/06/2020

B number: 
B3545
Principal applicant name: 
Stephanie von Hinke | University of Bristol (UK)
Co-applicants: 
Title of project: 
School starting age: the role of gene-environment interactions
Proposal summary: 

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".

Impact of research: 
We are writing a "practitioners' paper" on estimating gene-environment interplay in economics. This paper will focus on how the environment as well as genetic information can be incorporated within this framework, highlighting the role of endogeneity, measurement error, the interpretation of polygenic scores, and the inter-relatedness of genes and the environment. We would like to include the above application in this paper, investigating the importance of gene-environment interactions in the timing of birth relative to 1 September. With the increasing availability and use of genetic information in social science research, we believe this paper will be read widely across the social sciences.
Date proposal received: 
Monday, 25 May, 2020
Date proposal approved: 
Tuesday, 26 May, 2020
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Social science, Statistical methods

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