Proposal summaries
B4322 - Placental methylation - pilot study - 15/05/2023
We aim to investigate whether it is possible to obtain methylation data on the stored G0 placentas.
B4320 - The Genetics of Laterality- Causes and Consequences - 17/05/2023
Handedness refers to the preferential use of one hand over the other. Conversely, ambidexterity refers to the ability to perform the same action equally well with both hands. Hand preference is first observed during gestation as embryos begin to exhibit single arm movements. Across the life span, the consistent use of one hand leads to alterations in the macromorphology and micromorphology of bone, which results in enduring asymmetries in bone form and density. At the neurological level, handedness is associated with the lateralization of language (the side of the brain involved in language) and other cognitive effects. The prevalence of left-handedness in modern western cultures is approximately 9% and is greater in males than females. While handedness is conceptually simple, its aetiology and whether it is related to brain and visceral (internal organ) asymmetry is unclear.
Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we recently conducted the world’s largest genetic study of handedness in over 1.7 million individuals (Cuellar-Partida et al 2020). We found 41 genetic loci associated with left-handedness and 7 associated with ambidexterity (P < 5 × 10−8). We would now like to take this work forward and use the ALSPAC resource to investigate the relationship between these genetic variants and other measures of laterality including footedness and ocular dominance. We will perform latent class analyses of handedness, footedness and ocular dominance and examine how these latent classes relate to known genetic variation for handedness, as well as how the latent classes and handedness variants relate to early life physical and cognitive measures.
B4319 - Adverse Childhood Experiences and Gambling - 04/05/2023
Gambling disorder (persistent/recurrent gambling) can be harmful to health/social wellbeing. Previous research suggests that stressful life events, such as child maltreatment increase likelihood of gambling disorder. However, these studies rely on young adults remembering if stressful life events that happened long ago, rather than asking about these events close to when they happened. We also do not know much about the influence of other types of Adverse Childhood Experiences (e.g. parental mental health problems). We plan to look at the influence of a range of Adverse Childhood Experiences on gambling disorder, using data that have followed individuals up regularly since birth until their 30's.
B4312 - Association of child maltreatment and neurodevelopmental traits with cardiometabolic markers in young adults - 03/05/2023
Child maltreatment and childhood neurodevelopmental disorders (Autism and ADHD) are both associated with increased risk of cardiovascular disease and premature mortality in adulthood. Child maltreatment and neurodevelopmental disorders commonly co-occur. Previous work has explored the associations of these exposures individually with adult outcomes but not explored them together. This study aims to explore the association of neurodevelopment and maltreatment with cardiovascular risk factors in young adults, in particular looking for any interaction between the two exposures.
B4313 - Predicting outcomes for autistic children - 03/05/2023
Autistic may people face challenges with living independently, employment and education, mental health and quality of life. Different autistic people face challenges in different areas, and the extent of the difficulties they face may vary. This project aims to use data from existing studies of autistic people, to provide predictions of areas where difficulties are more or less likely, based on an individuals characteristics and experiences. This project will pool data from multiple studies, including ALSPAC, to give a larger sample size and allow comparisons of model performance in different settings.
B4284 - Normative modelling of brain structure in subjects with subclinical psychotic symptoms - 03/05/2023
Our proposal will exploit longitudinal neuroimaging to evaluate how brain maturation is linked with subclinical psychotic experiences. We have recently developed a method that allows us to identify abnormal maturational trajectories by computing brain centiles (analogous to pediatric growth charts). Applying this methodology to neuroimaging data from individuals with varying levels of psychosis will provide a more complete picture of how this condition progresses in the context of a normative population. Using ALSPAC data from subjects with psychotic experiences will enable us to study how early brain alterations are linked with an initial set of subclinical symptoms and will shed light on how these structural alterations compare to those seen in clinically diagnosed psychotic disorders in the context of a large-scale, multi-study framework.
B4318 - Mental-physical health multimorbidity in children and young people causal determinants and consequences - 03/05/2023
Multimorbidity is the presence of multiple long-term health conditions. People with multimorbidity tend to have worse quality of life, and to be high users of the health service. Mental-physical multimorbidity (MPMM) is a specific form of multimorbidity, typically defined as the presence of at least one mental health condition and at least one physical health condition. People who experience MPMM have more complex health needs than people with only physical health problems or only mental health problems. Each set of health problems may make the challenges of the other set worse, leading to worse quality of life for these patients. Poverty and other measures of deprivation are strongly linked to MPMM, making it a key driver of health inequality.
Research on MPMM is limited, but most studies that do exist focus on adults. However, data from primary care records suggest that 2.5% of 10-19 year olds and 11.1% of 20-29 year olds have MPMM. The true level of MPMM in children and young people will be much higher than this, as many health conditions, particularly mental health conditions, are poorly recorded in health records. Children and young people who already have MPMM are likely to go on to experience complex health needs across their life course, and represent a challenging group for the health service. Understanding who comprises this group, and the determinants and consequences (both for the health service and for the young people themselves) is crucial to identify potential intervention points to reduce the incidence of MPMM and to mitigate its adverse consequences.
In this project, we use birth-cohort data from three studies in the UK and Brazil to explore how and when MPMM occurs in children and young people, estimating the prevalence of overall MPMM and of specific combinations of health conditions. We will also examine the causal determinants of MPMM, and the consequences for young people (including education, employment, pain, health-risk behaviours, and wellbeing) and the health service. Studying both causes and consequences will allow us to reach conclusions about potential intervention targets both for preventing MPMM and for mitigating its adverse effects, and to quantify the potential gains from interventions to prevent MPMM or supporting young people with MPMM. Using data from both a high income country and a middle income country allows us to explore setting-specific patterns, causes, and consequences of MPMM – essential for understanding how tailored interventions must be to the local setting. Using birth cohort data allows us to circumvent the problems of under ascertainment of health conditions in administrative health records; linked health data in the UK cohorts will allow us to quantify this problem.
B4311 - Youth Criminal Activity and Desistance from Crime the role of protective early social and educational factors - 03/05/2023
Most research on youth criminal behaviour and recidivism (the tendency for an offender to reoffend) focuses on risk factors, and the literature often describes protective effects of the lack of a risk factor. However, the absence of a risk factor is not inherently protective and a deeper understanding of protective factors is useful in designing public health interventions. Protective factors explored in the literature are: social and emotional support, family support and connectedness, engagement in religious activities, school connectedness, and educational attainment. While there is some initial evidence suggesting these factors are protective against crime and/or promote desistance, this evidence is limited and much of it comes from adult samples and samples outside the UK. This project will use ALSPAC data to examine the role of early life and educational factors in protecting young people from offending, and in promoting desistance.
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.
B4314 - Gambling data analysis 30 - 15/05/2023
This analysis will examine the gambling behaviour of participants at age 30, including online gambling, betting on esports and using cryptocurrency to gamble. It will compare the findings at age 30 with previous data on gambling collected at ages 17, 20, 24 and 28 to provide a rich longitudinal picture of gambling activity among young people.
B4297 - Is waist circumference to height ratio an alternative tool for predicting metabolic risk above that achieved with BMI - 24/04/2023
Studies have suggested that waist (cm)/height (cm) ratio (WC/H) is a useful alternative measure of central adiposity and obesity related metabolic risk in adults and children than body mass index (BMI) (1-3). In practice, BMI has shown poor performance in certain cohorts and does not indicate an individual’s distribution of fat. WC/H focuses on central adiposity, a known cardiometabolic risk factor for adults and children. Furthermore, calculating BMI requires weighing equipment, a calculator and potentially software/charts. WC/H only needs a tape measure, uses a simple calculation and has a pre-defined ratio to define risk across participant types (cited as >0.5).
NICE have recently recommended the use of WC/H alongside BMI to assess and predict weight-related conditions. There is currently a paucity of research describing the life course patterns of WC/H or demonstrating that it provides equal or improved prediction in metabolic health from childhood to adult life compared to BMI. There is also little evidence relating WC/H to outcomes or intermediates related to central adiposity in particular – e.g., hypertension and non-alcoholic fatty liver disease.
This study aims to 1) chart the trajectory of WC/H compared to BMI through ages 7, 11, 15 and 24, 2) examine associations of WC/H or BMI, and blood pressure and liver health at these ages and 3) compare these associations to explore if WC/H is more discriminatory in defining risk. This will provide additional evidence for the recommendation of an easier measure to assess clinical need for weight management interventions across childhood and adolescence.
References
1. Ashwell M, Gibson S. Waist-to-height ratio as an indicator of 'early health risk': simpler and more predictive than using a 'matrix' based on BMI and waist circumference. BMJ Open. 2016 Mar 14;6(3):e010159.
2. Savva SC, Tornaritis M, Savva ME, Kourides Y, Panagi A, Silikiotou N, Georgiou C, Kafatos A. Waist circumference and waist-to-height ratio are better predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat Metab Disord. 2000 Nov;24(11):1453-8.
3. Khoury M, Manlhiot C, McCrindle BW. Role of the waist/height ratio in the cardiometabolic risk assessment of children classified by body mass index. J Am Coll Cardiol. 2013 Aug 20;62(8):742-51.
B4310 - Meta-ewas of breast feeding - 24/04/2023
This project aims to assess the association between DNA methylation and breastfeeding using data from ALSPAC and other birth cohorts with similar data. Breastfeeding has both short and long term beneficial effects on child health. DNA methylation is a molecular mechanism which might mediate the relationship between breast feeding and beneficial health effects in children but we do not yet have good evidence to show if DNA methylation is associated with breast feeding. This research aims to answer this knowledge gap.
B4316 - Metabolomic signature of air pollution exposure in children - 24/04/2023
Previous research has shown association between exposure to long-term air pollution and adverse lipid profiles. Fewer studies have been performed using metabolomics, which identify and quantify small molecules to represent an organism’s metabolic state. A metabolic signature in the blood associated with ambient air pollution exposure is plausible given some ambient air pollutants (ultrafine particles and gaseous air pollution) have been reported to enter the bloodstream directly from the lungs. Most research in this area has focused on adulthood, and little evidence is available in younger ages. This study aims to assess the metabolomic signature of air pollution in childhood.
B4317 - Air pollution and inflammation in childhood adolescence and early adulthood - 24/04/2023
Exposure to air pollution has been associated with poorer cardiovascular health and cardiovascular disease, and inflammation is one of the postulated mechanisms of this relationship. Most studies have investigated the association between air pollution and inflammation using C-reactive protein (CRP), particularly in adulthood. Evidence in younger ages and using other inflammatory markers is limited. This study will explore the association between air pollution and inflammation from childhood to early adulthood using different inflammatory markers.
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.