Proposal summaries
B4302 - Mediating pathways between childhood autistic traits and adolescent disordered eating behaviours - 24/04/2023
Research suggests that children with autistic symptoms have an increased risk of experiencing symptoms of eating disorders in adolescence. However, it is still not clear which experiences lead to this increased risk. Previous studies have shown that autistic children are more likely to be bullied and have symptoms of depression. These are also plausible risk factors for eating disorders and could be addressed by interventions, but no research has investigated these pathways yet.
B4303 - Using statistical and machine learning approaches to predict study drop-out in ALSPAC - 24/04/2023
In longitudinal cohort studies such as ALSPAC, participants may decide to leave the study or become inactive (not replying to questionnaires or attending clinics). This can both reduce the statistical power of studies using these data and introduce bias as the remaining participants tend to be a non-random subsample. We will use machine learning and statistical approaches to determine the extent to which study dropout can be predicted at different ages, and what participant characteristics predict it.
B4309 - The relationship between behaviour/emotional problems and paediatric incontinence - 24/04/2023
Observational studies in children and adolescents have found evidence for prospective associations between behaviour/emotional problems and incontinence. Although prospective studies reduce the likelihood of reverse causation, they are limited by residual confounding.
B4301 - Guidelines for releasing de-identified synthesised data from the Avon Longitudinal Study of Parents and Children - 12/04/2023
The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective birth cohort, based in and around Bristol, UK. Maintaining data security and participant anonymity and confidentiality are key principles for the study, hence why data access is restricted to bona fide researchers and ALSPAC data are not openly available. Despite these valid reason for restricting data availability, this position is somewhat in conflict with emerging best scientific practices, which encourage making data openly available to facilitate reproducible and replicable open scientific research.
Given the rich nature of the resource, ALSPAC data may also be valuable as a educational tool, such as for teaching methods such as longitudinal modelling or approaches to modelling missing data. To aid these efforts, we want to assess methods for generating and making openly-available synthesised ALSPAC data; these synthesised datasets are modelled on the original ALSPAC data, thus maintaining variable distributions and relations among variables, while at the same time preserving participant anonymity and confidentiality. We will explore how data can be synthesised using the ‘synthpop’ package in the R statistical programming language, and aim to present a list of guidelines which all researchers wishing to release such synthesised ALSPAC data must follow.
B4305 - Primary prevention of depression and anxiety in youth Which at-risk groups to target and when - 12/04/2023
Depression and anxiety are debilitating conditions that often start in late adolescence and young adulthood.
Understanding who is at the most risk of these conditions is important because it can help to target and tailor preventative approaches.
This project will aim to identify the smallest group associated with the largest amount of new cases of depression and anxiety.
B4307 - The role of cognitive and emotional processing in the association between adverse childhood experiences and crime in adulthood - 12/04/2023
Crime in adulthood is a well-established long-term consequence of childhood adversity, but the exact mechanism underlying this process is not well known. One mechanism suggested by research is that childhood adversity results in impaired neurobiology, emotional and executive functioning, and self-regulation. Disrupted emotional processing is linked to behavioural problems such as conduct disorders due to an impaired ability to recognise certain emotions, namely anger and fear, with the latter being linked to increased violence. Impaired executive functioning is hypothesized to lead to decreased inhibitory control and cognitive flexibility, while disrupted self-regulation is linked to increased aggressiveness due to an inability to regulate one’s thoughts, actions, and emotions. These deficiencies and their outcomes have been linked to crime, especially violent crime. However, other factors such as genetics, socioeconomic status and alcohol use can increase the likelihood of experiencing additional adversity while also influencing the nature and extent of these impairments. The resulting differences in cognitive and emotional impairments may result in different types of crimes being committed. We hope that better understanding of the processes mediating adverse childhood experiences (ACEs) in children and crime in adulthood can inform more precise therapy employed by clinicians treating these ACEs, as well as more cost-effective measures for policymakers to target the effects of these ACEs in vulnerable populations.
B4308 - The relationship between autistic traits continence problems and constipation - 12/04/2023
Autistic traits refer to characteristics commonly seen in individuals with autism spectrum disorder (ASD), such as difficulties with social interaction and communication, repetitive behaviours, and restricted interests (1). Some studies have suggested that individuals with ASD may have a higher risk of experiencing constipation and continence problems (2, 3). This may be due in part to sensory processing difficulties that can affect the way individuals with ASD perceive and respond to bodily sensations, including those related to bowel and bladder function (3). In addition, some individuals with ASD may have dietary restrictions or preferences that could contribute to constipation such as avoiding certain textures or types of food (3).
Further research is needed to better understand the relationships between these problems (constipation and continence) and autism and to develop effective interventions for individuals who experience these problems. Although several clinical studies have been conducted in the past to investigate these relationships (4), to the best of our knowledge, no population-based studies have been done. This research will examine relationships between autistic traits and continence and constipation in children and adolescents in the ALSPAC cohort.
B4304 - Human fetal and postnatal brain size scaling and function effects of a constrained intrauterine resource environment - 15/05/2023
This project aims to understand growth during and after a pregnancy in which the placenta is faulty and less able to nourish the fetus, and its impact on the key developmental brain function of sleep, via mathematical modelling.
Growth is a crucial part of healthy development. So, it is important to understand what happens when growth is impaired. In some pregnancies, the placenta cannot transfer as much oxygen and sugar to the fetus as required. To deal with this, the fetus prioritises its most important organ - the brain - and directs most oxygen and sugar there. This results in the size of the brain relative to the body being larger than usual.
Sleep is a key developmental brain function, supporting the formation of memories. This is why babies spend up to 97% of their time asleep. Because sleep occurs to help our brain but also the rest of our body, the size of the brain relative to the body explains for how long we need to sleep. We believe that the brain growing too large relative to the body may disorganise sleep, and make it less good at helping to form memories. This could explain why infants who grow like this sometimes have later learning difficulties.
In this project, we are going to collate and collect data which will allow us to mathematically test our theory that faulty growth impairs sleep. The results will help to understand this condition better, and could suggest new ideas for personalised therapies, e.g. that strengthen sleep.
B4295 - Looking through the epigenome to better understand ADHD and co-occurring psycho-neuro-behavioural traits - 06/04/2023
Attention-Deficit Hyperactivity Disorder (ADHD) has symptoms of inattention, hyperactivity, or both. However, patients with ADHD often experience symptoms of other disorders such as autism spectrum disorder (ASD), epilepsy, conduct disorder, or anxiety symptoms. Previously, it was reported that there are shared heritability and cognitive process across the conditions, implying that there are common underlying biopsychological factors that have not been identified.Epigenetic biomarkers, especially blood DNA methylation (DNAm) became significantly important in understanding neurodevelopmental disorders such as ADHD. Even though the associations between DNAm and each condition were investigated, there is a limited amount of research on DNAm biomarkers across ADHD-related phenotypes (ADHD and co-occurring symptoms). We hypothesized that the underlying biological factors would be specific to clusters of conditions and could be used as a diagnosis factor for children. Therefore, we propose to investigate the relationships between each of the individual traits linked to ADHD and DNAm to reveal their epigenetic similarities and differences. The epigenetic similarities and differences will give in-depth insight to understand ADHD. We will use a series of computational methods including EWAS and machine learning to investigate the DNAm biomarkers of complex ADHD-related phenotypes from around 1500 participants from the Avon Longitudinal Study of Parents and Children.
B4293 - The role of individual differences in pro-environmental behaviour - 06/04/2023
There are several studies that have examined the role of personality in pro-environmental attitudes or behaviours. However, they typically investigate either attitudes or behaviours. Environmental attitudes and behaviours have been identified as an area with a significant gap between attitude and behaviour. We wish to address this gap by examining whether personality traits are predictive of both attitude and behaviour, and whether those who have pro-environmental attitudes and perform pro environmental behaviours differ from those who do not. Using the ALSPAC dataset will allow us to examine personality and its role in pro-environmental variables longitudinally.
B4294 - The role of childhood personality traits in adult mental health symptoms - 06/04/2023
Previous research has found partial evidence for a role of personality traits in mental health outcomes. However, many of these studies do not examine all of the big 5 personality traits simultaneously, examine mental health generally, or a small number of mental health symptoms. These studies also tend to examine participants cross-sectionally, without examining the way in which personality traits may influence mental health longitudinally, after controlling for confounders. This study aims to overcome the previous patchwork coverage of this topic by combining a range of exposure and outcome variables in a prospective cohort study.
B4296 - Prevalence of mental health need among 0-4 years old in England - 06/04/2023
The National Mental Health Intelligence Network (NMHIN) has been commissioned by NHSE to determine whether an estimate of mental health need for 0–4-year-olds can be produced, with the aim of being able to produce national and local area prevalence estimates for this age group.
This work included an initial feasibility assessment which was advised by an expert reference group (ERG) of experts in the field. The ERG gave a strong steer of using an existing cohort study that assesses the mental health of the children in this age group, considering limited availability of data around the topic which can be generalized at national level.
Currently, we are looking at developing an interim national prevalence that gives an estimate of mental health need among this age group. This will be done by selecting a study sample from ALSPAC, looking at the mental health outcomes of the study group and then applying the prevalence at a national and local level.
B4299 - Understanding the trajectories of adolescent and early adulthood depression outcomes of attention deficit hyperactivity disorder - 06/04/2023
Individuals with Attention deficit hyperactivity disorder (ADHD) may be more likely to suffer from mental health problems than the general population. We aim to investigate the relationship between ADHD and depression using data from a longitudinal study of over 14000 children born in the early 90s with ongoing data collection. We will investigate whether specific risk factors such as bullying and childhood adversity may influence this relationship and act as modifiable targets for intervention.
B4300 - STAGE Stay healthy through ageing - 06/04/2023
The prevalence of multimorbidity increases with age. Therefore, to prevent it and mitigate its impacts, we need to understand how multiple factors at different stages of the life course affect an individual’s health trajectory with ageing.
Currently, an important knowledge gap exists in this area as most research has focused on single life stages and/or single diseases, and often only at adult ages when multimorbidity appears. This overlooks the sequence and dynamic development of comorbidities in the life course.
We will address this gap by creating trajectories of multimorbidity by disease, physiological function and medication usage across all life stages.
B4279 - Investigation of impacts of colour blindness on educational and psychological outcomes v2 - 03/04/2023
X-linked, red-green colour blindness (CVD) is a congenital condition affecting 8% of men (0.4% of women). Depending on type and severity, affected individuals have significant difficulties discriminating a wide range of colours facing wide-ranging challenges on a day-to-day basis (e.g. interpreting colour-coded information at the workplace or recreational environments). A growing impact is expected in educational settings due to an increasing reliance on colour resources in schools. Unfortunately, a study using a birth cohort from 1958 (Cumberland et al, 2004) has reported a lack of impact of colour blindness on Maths and reading ability but fails to account for the increase in colour in classrooms in recent years. Regrettably the publication led to the cessation of CVD school screening in 2009, preventing children from accessing more appropriate resources.
In contrast, a number of authors have argued that CVD can increase difficulties experienced in a range of school subjects including Sciences, Maths, Art, PE and Geography as such subjects may use colour to explain concepts, give instructions and require it in problem solving tasks. Alongside any academic implications, CVD has been found to have an effect on social, psychological and emotional outcomes. For example CVD children may experience teasing from classmates.
We here propose to investigate the potential impacts of CVD on education and emotional outcomes in a more recent cohort.
B4283 - How are Adverse Childhood Experiences Linked to Depersonalisation Biological Mediators and Psychosocial Risk Factors - 27/03/2023
Depersonalisation disorder (DPD) is a distressing condition that typically emerges in young adulthood, characterised by detachment from one’s body and self, and/or one’s environment. Individuals with DPD retrospectively report adverse childhood experiences (ACEs) and are objectively evidenced to have a dysfunctional biological stress system. However, no research has looked at the biological mechanisms that translate ACEs into DPD later in life. Using self-report and biological data of parent-child dyads from the Avon Longitudinal Study of Parents and Children (ALSPAC), I aim to fulfil this research gap. Within the ALSPAC data, instances of childhood sexual, emotional, and physical abuse, emotional neglect and family dysfunction are reported separately by both parents (during annual assessment of the child’s development), and by the child (later in life), which can be combined, creating a measure of ACEs that doesn’t rely solely on retrospective reports. Stress system dysfunction is measured by cortisol (a stress hormone) level, interleukin-6 and C-reactive protein (measures of inflammation). At ages 12 (N = 6832), 17 (N = 5217) and 24 (N = 4021), symptoms of DPD were assessed. Using statistical modelling, I am examining whether the accumulation and the timing of childhood abuse translates into DPD symptoms, mediated by abnormal cortisol and inflammation levels. Additionally, factors with potential to provide risk for, or resilience against, developing DPD symptoms are also being evaluated to provide a comprehensive representation of how DPD symptoms may develop. These include sleep, drug use, attachment, maladaptive cognitions and social position.
B4286 - The role of prenatal alcohol exposure in predicting criminality A cohort study - 27/03/2023
Studies conducted using animals have been instrumental in describing the brain impairment and physiological processes that cause prenatal alcohol exposure (PAE). Research has shown that similar brain and physiological features are likely to be affected in those displaying
increase criminality and behavioral disorders. Some features affected include inattention, impulsivity, the poor executive functioning, impulse control, memory and cause and effect thinking.
Fetal alcohol spectrum disorder (FASD) is attributed to the effects of PAE, and has been associated with a two to six fold increase in mental disorder diagnosis in offsprings of alcohol binge drinking mothers. Youths with FASD are 19 times more likely to end up incarcerated than those without. Cigarette smoking and illicit drugs used in pregnancy also contribute to adverse pregnancy outcomes and are important risk factors of criminality.
Offspring of mothers who drank during pregnancy especially heavy drinking of greater than 21 units a week, will be at an increased risk for adolescents antisocial activities and conversely criminal activities in adulthood. It is also likely that there is a positive relationship between the quantity of alcohol used and number and intensity of antisocial activities and criminal activities.
B4261 - Genomics metabolomics and inflammatory markers and Eating Disorders and related behaviours across the life span and generations - 27/03/2023
Eating Disorders (ED) (full and partial syndrome anorexia nervosa and bulimia nervosa and binge eating disorder) are life- threatening illnesses that start in adolescence and affect between one and two in ten adolescents and young adults. There is a lack in our understanding of why eating disorders develop, which affects our ability to develop treatment and adequately prevent eating disorders. This project builds on our previous studies in ALSPAC, showing that metabolism and growth might play a role in the development of eating disorders. We aim to combine metabolic function, body composition, blood and inflammatory markers, as well as genetic information to understand progression and development of eating disorders and related symptoms in the 3 generations of ALSPAC participants. This study will be fundamental in understanding how eating disorders develop and progress across the life span.
B4278 - Evaluating the relationship between early life adiposity measures and later life disease susceptibility - 27/03/2023
Analytical approaches which disentangle heterogeneous effects on trait susceptibility provide important insight on the relationship between complex traits and disease. Lifecourse Mendelian randomization (MR) is a novel statistical approach which has been developed to address lifecourse specific effects on disease susceptibility (1, 2, 3). Additionally, stratifying instrumental variables based on tissue derived gene expression data provides further molecular context to interpret the effect (4, 5).
Evaluation of the relationship between lifecourse and tissue dependent effects on biomarkers measured in early life provides important insight on key etiological and susceptibility windows of disease. The results of a recent analysis have provided evidence of a direct effect for the brain-mediated component of body-size on the adipose tissue secreted hormone leptin measured at age 10 in the lifecourse (Richardson et al, in revision). Through the integration of tissue-specific data, this approach highlights the etiological importance of appetite regulation in the links between adiposity and leptin levels in early life.
Additionally, this study also showed evidence for an effect of adult body-size on circulating leptin measured in childhood (when accounting for the effect of early life body size), which is directionally implausible. This raises the possibility that the adult derived exposure may be a strong predictor for traits in early life which have an effect on childhood leptin levels. In this project we will further characterize the relationship between adult body size and early life adiposity measures and a range of childhood biomarkers to refine the interpretation of this causal relationship.
References:
1. Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey Smith G. Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study. BMJ. 2020;369:m1203.
2. Richardson TG, Power GM, Davey Smith G. Adiposity may confound the association between vitamin D and disease risk - a lifecourse Mendelian randomization study. Elife. 2022;11.
3. Sanderson E, Richardson TG, Morris TT, Tilling K, Davey Smith G. Estimation of causal effects of a time-varying exposure at multiple time points through multivariable mendelian randomization. PLoS Genet. 2022;18(7):e1010290.
4. Leyden GM, Shapland CY, Davey Smith G, Sanderson E, Greenwood MP, Murphy D, et al. Harnessing tissue-specific genetic variation to dissect putative causal pathways between body mass index and cardiometabolic phenotypes. Am J Hum Genet. 2022.
5. Leyden GM, Greenwood MP, Gaborieau V, Han Y, Amos CI, Brennan P, et al. Disentangling the aetiological pathways between body mass index and site-specific cancer risk using tissue-partitioned Mendelian randomisation. Br J Cancer. 2022.
B4290 - Whole Exome Sequencing - Completing Coverage for all ALSPAC participants - 05/04/2023
Whole exome sequencing (WES) is a method used to generate the sequence of all protein encoding regions of the human genome. ALSPAC has already obtained WES data from all available DNA from G1 participants (original children) and a subset of G0 parents. ALSPAC has been included in an MRC funded initiative to complete WES sequencing in some cohort studies. This will fund generating WES on approximately 11,000 samples from the remaining G0 parents and G2 (CoCo90s). This, together with existing data, will ensure WES is available from all suitable ALSPAC DNA samples.