Proposal summaries
B4558 - Childhood Obesity and Overweight GWAS for the EGG consortium - 23/04/2024
Obesity is a common health problem. Obesity can start early in life, and it is thought that genetic factors may be important in people who become obese at a young age. Little is known about these genetic factors in children compared to adults. An international effort co-ordinated by the Early Growth Genetics consortium (EGG) is currently underway which aims to test for genetic effects on different measures of overweight and obesity in childhood. This proposal plans to carry out analysis of different measures of overweight and obesity in children in the ALSPAC cohort, and plans to share summary results of this analysis with EGG.
B4552 - Early regulatory problems and adverse health and social outcomes in adolescence - 11/03/2024
Developing good self-regulation skills is one of the most important tasks for a child to accomplish. Earliest signs of difficulties in self-regulation include excessive crying, sleeping, or feeding difficulties, which are labelled as ‘regulatory problems’. Increasing evidence has shown that regulatory problems in infancy/toddlerhood increase the risk of several negative outcomes such as attention problems, emotional and behavioral dysregulation in childhood, and depressive symptoms in adolescence. However, it remains unknown if regulatory problems in infancy/toddlerhood are also associated with adverse health and social outcomes in adolescence.
The current study aims to investigate whether regulatory problems in infancy/toddlerhood increase the risk of following adverse a) health outcomes in adolescence: harmful drinking, smoking, cannabis use, illicit drug use, problem gambling, unwanted pregnancy, obesity, excessive screen time, and self-harm at 18 years, and b) social outcomes in adolescence: getting into trouble with police, not being in education, employment or training (NEET), low peer social support, low closeness in romantic relationships and relationship with parents.
B4557 - Investigating the relationships linking adverse childhood experiences to psychotic-like experiences - 11/03/2024
Psychosis is a severe mental health problem whereby sufferers lose some contact with reality. Two main symptoms of psychosis are hallucinations, where people hear or see something that others cannot, and delusions, where a person has strong beliefs that are not shared by others. People with a psychotic disorder are approximately 2-3 times as likely to have had adverse childhood experiences (ACEs) compared to those without this diagnosis. However, the exact mechanisms linking childhood trauma to psychosis and whether certain characteristics can reduce this risk are unknown. The prevalence of psychotic symptoms reduces from childhood into early adulthood, suggesting that most psychotic experiences in young people are short-term. However, less is known about what factors may predict the persistence of these symptoms. Much of the literature investigating the role of ACEs in the onset of psychosis has been based on study designs which only provide weak evidence about causation. For example, much of the literature relies on case-control studies which can only detect associations, rather than causal relationships between ACEs and psychosis, as a third, unaccounted variable may explain the association.
This project will examine:
(1) The trajectories of psychotic experiences from childhood into early adulthood and whether exposure to ACEs predicts the persistence of symptoms;
(2) whether social factors and cannabis use make the relationship between ACEs and psychosis stronger or weaker; and
(3) pathways linking ACEs to psychosis, namely cannabis use, self-esteem and PTSS (posttraumatic stress symptoms).
B4554 - Investigating physical and mental health multimorbidity determinants throughout the lifespan - 13/03/2024
Multimorbidity (MM) happens when two or more different diseases are present at the same time in an individual. This is common between physical and psychiatric diseases with almost half of people with a psychiatric disease also having a physical disease. As well as about a third of people with a physical disease also having a psychiatric disease. These patients have worse quality of life than those with a single disease, they often struggle to get the best care and are at risk of living less long. A common and serious type of MM is between internalizing diseases (depression and anxiety) and cardiovascular disease (ICV-MM). Still, very little is understood as to how ICV-MM develops and why it happens. We do know however that both internalizing disease and cardiovascular risk (e.g., obesity, cholesterol) tend to begin before adulthood.
To really understand how ICV risk develops, we need large studies of people of all ages whose health has been followed over time. Studies of children are crucial because they can tell us about early risks for development of ICV-MM later in life. This is important for developing better plans to prevent at-risk children developing ICV-MM. We also know that certain conditions that start early in life (neurodevelopmental conditions) such as intellectual disability, autism and ADHD increase risk of developing ICV MM later. Children's environments can also increase this risk, for example, stressful experiences such as poverty and physical or sexual abuse. But how exactly neurodevelopmental conditions and early environmental risks influence the development of ICV-MM over the lifespan is still not understood. Certain groups are known to be at increased risk of ICV-MM, such as people of South Asian heritage and women, but we don't know why this is. Better understanding of how ICV-MM develops in different groups in society will help doctors give patients care that is matched to their specific needs. It will also help doctors, governments and schools prevent ICV-MM in at-risk children in ways that work best for them.
To really understand the complexities of ICV-MM development, a team of researchers with a wide range of expertise is needed who together understand physical and psychiatric diseases as well as how neurodevelopmental conditions and the environments people live in influence them throughout their lives. The PhD student will benefit from working within our LIfespaN multimorbidity research Collaborative (LINC), which combines wide-ranging medical and research expertise in physical and psychiatric diseases. LINC has brought together five very large studies (of which the student will access two – ALSPAC and UK Biobank) in which the health of many people has been followed over time. Rich medical data is available, including from medical records. Important information has been collected such as on people's living environments, life events and lifestyles. These studies follow the health over time of children, adolescents and adults. We can therefore study how internalizing and cardiovascular disease happen together in adulthood. Importantly we can then also study early risk factors in the children before they develop these conditions. Because our child and adult samples differ in ethnicity and economic situation, we can also study how the development of ICV-MM differs for different groups in society. The student’s studies will further LINC’s efforts in understanding how ICV-MM develops and which circumstances influence this. What we learn will be important for the prevention of ICV-MM in children who are at risk because of their sex, or ethnic or economic reasons. The student will disseminate their research to Welsh government, patient and public involvement groups and charities to develop specific health advice in order to reduce ICV-MM in at risk groups in the future.
B4555 - Can arts engagement protect against common mental health issues in children and young people - 05/03/2024
This project sets out to investigate whether involvement in the arts can play a role in preventing anxiety, depression, and eating disorders among young people. By analysing data from large community studies tracking the development of children over time, we aim to achieve four main objectives:
1) Current Relationship: We will look into the connection between participating in the arts and the mental health of young individuals at the present moment.
2) Future Impact: We aim to understand if there's a link between participating in the arts at one time and later mental health outcomes of young people. This will help us determine if arts involvement could potentially act as a preventive measure against mental health issues.
3) Variations Across Time and Countries: Through comparing data from different cohorts, we will explore whether the relationship between arts engagement and mental health outcomes varies over time and across different countries.
4) Arts engagement as a protective factor: We will explore whether arts engagement may protect against later mental illness in children experiencing socioeconomic adversity using mediation methods.
By undertaking this careful analysis, we hope to provide high-quality evidence regarding the potential benefits of arts engagement in promoting good mental wellbeing in young people. This research could inform interventions and policies aimed at promoting mental health through creative activities, potentially offering valuable insights into preventive strategies for anxiety, depression, and eating disorders among young individuals.
B4549 - Investigating the associations between ADHD sleep disturbance and comorbid mental health outcomes across the lifespan Part 2 - 04/03/2024
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common diagnosis. It affects around 3% of the population. ADHD has symptoms of hyperactivity, inattention, or both. Although ADHD is usually seen in childhood, it is now accepted that for many, ADHD persists into adulthood. Adults with ADHD are more likely to also have symptoms of depression and anxiety. Without effective management, this can make life more difficult for someone with ADHD.
Both children and adults with ADHD also often report sleep problems. Getting good quality sleep is crucial to someone's health. Sleep problems are also a key aspect of mental health conditions, including anxiety and depression. In this proposal, we set out how we aim to investigate what role sleep disturbance plays in both ADHD and mental health.
This project will use existing measures collected from consenting ALSPAC participants. In particular, we will use measures of ADHD symptoms, sleep, anxiety, and depression. Through statistical analysis, we will explore whether ADHD influences someone's sleep quality. We will build on this by exploring whether a relationship between ADHD and sleep goes on to impact someone's mental health.
Our findings may have consequences for how we view the importance of sleep for someone with ADHD. Crucially, sleep is a modifiable behaviour. Our results may help promote clinical recommendations that consider sleep as a key component of ADHD management.
This proposal will use the dataset for B4541 only. No new data is required.
B4543 - Associations of air pollution exposure with epigenetic age at birth and in childhood a meta-analysis LongITools - 04/03/2024
Early-life exposure to ambient air pollution has been associated with adverse birth outcomes and poorer health across the life course. The mechanisms underlying these associations are still unclear, but differential DNA methylation might be involved. Nitrogen dioxide (NO2) and particulate matter (PM) exposure in pregnancy have been found to be associated with newborn DNA methylation. The objective of the present study is to examine the associations of air pollutant exposure during early life with epigenetic age acceleration at birth, in childhood and in adolescence in a multi-cohort setting.
B4546 - Social Inequality in child mental health difficulties Understanding epigenetic and family pathways - 04/03/2024
Social inequality is the unequal distribution of socio-economic (SES) resources which affects people’s standards of living. Typically, individuals from lower SES backgrounds have a higher risk of poor physical and mental health, and children, have an increased likelihood of developing emotional and behavioural difficulties. Multiple factors such as family stress or genetics can influence this relationship between SES position and mental health difficulties. For example, low family income can contribute to difficulty in affording needs and parental distress, which in turn may lead to harsher parenting or family conflict which affect child development. Some of the exposures associated with low SES position can lead to heritable changes in gene expression without altering the DNA sequence which could then affect mental health outcomes. These changes are known as epigenetics, and DNA methylation (DNAm) is the most common epigenetic mechanism through which social inequality can affect gene expression. Low SES position has been previously associated with more alterations to DNAm profiles compared to higher SES positions. DNA methylation occurring in some gene regions have also been observed to associate with child mental health difficulties. Therefore, in this study we propose to investigate the relationship between SES position and child mental health difficulties, and whether this relationship can be explained by epigenetic changes and family functioning. We will make use of multiple methods, most notably structural equation modelling (SEM) for longitudinal analysis of participant data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
B4553 - Pregnancy history of ALSPAC G1 participants - 04/03/2024
We will prepare a complete history of pregnancies for ALSPAC G1 female participants and those of G1 male partners.
This will help us to identify participants who have never enrolled in G2 and ensure we have the correct information for those who have enrolled. We plan to provide summary data for other researchers and produce a data note explaining the variables we have derived.
B4550 - Is persistent childhood irritability a core feature of ADHD - 05/03/2024
Severe irritability, characterized by an elevated disposition towards anger and provocation relative to peers, is highly impairing, disruptive and a common reason for referral to mental health services. It also co-occurs with several different mental health and neurodevelopmental conditions, such as ADHD, autism, anxiety, and depression. Importantly, severe irritability is currently classified differently in European (ICD-11) and American (DSM-5) diagnostic manuals, either as a behavioural or mood problem, respectively. A high prevalence of irritability in children with ADHD, along with genetic overlap, has also led to the hypothesis that irritability may be a core feature of ADHD, a neurodevelopmental condition. Recent research suggests that irritability may be different (e.g., more related to ADHD or mood/depression phenotypes) depending on the age when symptoms commence. Research that spans different ages is therefore very important. This project aims to test the hypothesis that childhood-onset persistent irritability, resembles ADHD in its developmental course and aetiology.
B4545 - Prediction of persistent atopic dermatitis in childhood a comparative study of birth cohorts in diverse settings - 01/03/2024
Eczema (atopic dermatitis) is a skin condition which causes dry and sore skin. It affects up to 20% of children worldwide. In some children their eczema symptoms will improve and resolve as they get older, but in others the symptoms can persist throughout childhood and severely impact quality of life. If we could identify the children who are likely to go on to have persistent or severe eczema, they could be offered more intensive or different treatment for their eczema. There have been several studies to define subtypes of eczema, such as early-onset resolving or persistent, and to try to identify which early life factors are associated with each subtype. However, the evidence so far is conflicting, there are no clinical risk prediction tools available, and most studies have only involved children of European ancestry. There is a critical need for a clinical risk prediction algorithm that could facilitate teat decision-making in clinic and inform whether emergent treatments are disease-modifying.
This study will analyse existing data from birth cohort studies which include children from a range of ethnic groups. Within each cohort we will group children with eczema into subgroups, according to the age at first symptoms, whether the symptoms come and go over time or are persistent, and the severity of the symptoms. Then we will investigate whether persistent or severe eczema (compared to resolving eczema) is linked to early factors such as family history of eczema, sex at birth, birth weight, ethnicity, breastfeeding and genetic factors.
We will develop prognostic models to help counsel parents on treatment decisions and stratify patients in future clinical trials. Within each cohort, we will also examine a longer list of early life factors that may be more challenging to measure to examine how much they increase the utility of the prognostic models. Comparison of the findings between cohorts will identify common predictors of persistent eczema which could help target treatment to children at risk, and identify areas that may require additional focus.
B4547 - Dynamic complementarities in human capital - 05/03/2024
The goal of the European Social Science Genetics Network (ESSGN) is to integrate genetic information in the social sciences to improve our understanding of a range of long-standing questions, including the roots of inequality, the 'nature versus nurture' debate, and the significance of the interplay between environments and genes in shaping individuals' lives. Building on the significance of teacher quality (proxied by teachers’ value-added in cognitive and non-cognitive skills) in influencing student outcomes, our study within the network aims to investigate whether children with low/high genetic predispositions to education benefit more/less to varying levels of teacher quality within the ALSPAC cohort. This investigation involves aligning data on teacher and school quality with genotyped parents and children from ALSPAC to investigate the influence of teachers on life chances, and potential moderation of this relationship by children’s genetic predisposition.
B4531 - Fetal and Infant Growth and Childhood Behavior and Cognitive Outcomes Individual Participant Data Meta-analysis 95000 children - 26/02/2024
In this project we will examine the associations of fetal and infant growth with behavior and cognitive outcomes in children between 4 and 15 years old. Specifically, we will evaluate the effect of birth weight, gestational age at birth, gestational age adjusted birth weight and internalizing and externalizing problems, attention-deficit hyperactivity disorder symptoms, autism spectrum disorder traits and non-verbal IQ. Furthermore, we will examine the associations of growth patterns between birth weight and infancy body mass index and the same behavior and cognitive outcomes. For this study, we will use harmonized data from birth cohort studies across Europe and analyze this data combined.
B4542 - Identifying markers for brain signatures of adolescent depression and depression risk - part 2 - 20/02/2024
We are requesting permission for a PhD rotation student to analyse existing data that is held at the University of Edinburgh under the proposal B3860. We do not require any more data, only to allow the student access to this data so they can replicate some analysis that has been done in Generation Scotland.
B3860 is examining: investigating the brain signatures of
adolescent depression and depression risk. In order to fully examine this project,
we are running some initial analysis to define the most robust markers of
depression across adolescence. From preliminary analysis and other research, we
have found that trajectories of depressive symptoms may be robust markers for
some brain signatures. Additionally, these trajectories could mediate the
relationship between early risk factors and later brain signatures.
B4535 - How Childhood Dietary Patterns Shape Adolescence-to-Early Adulthood Metabolic Health and Immune Response - 26/02/2024
A healthy, balanced diet is important for keeping metabolic health and supporting immune system. Obesity is associated with a wide range of metabolic syndromes, including dyslipidemia, hyperglycemia and fatty liver. Hyperglycemia and lipid accumulation may provoke lipid oxidation and further lead to an overproduction of cytokines, hyperactivation of complement system and activation of coagulation system, which all serve as immunological triggers to severe infection of COVID-19 as well as other infectious diseases. With the soaring prevalence of cardiometabolic diseases attributed to obesity and metabolic syndrome, the significance of dietary factors in this context is becoming increasingly emphasized. Mirroring the obesity pandemic in adults, paediatric obesity is also rapidly growing worldwide. As a consequence, metabolic dysfunction-associated steatolic liver disease (MASLD) has become the most common liver disease affecting children1. A concern about paediatric liver diseases is that the disease is likely to persistent into adulthood, conferring a substantial cumulative risk of progressing into chronic liver disease, as well as cardiometabolic dysfunction2. Beyond examining individual dietary components, such as fruits or red meat individually, the impact of overall dietary patterns during childhood on indicators of overall health outcomes, such as blood glucose levels, blood pressure, liver fat and chronic inflammation, in adolescence and early adulthood remain inadequately understood. Moreover, the advent of advanced omics technologies, such as metabolomics, provides a promising approach to elucidate the intricate mechanisms/pathways linking dietary patterns to health outcomes. In the current proposed project, we will explore all the potential associations between dietary patterns and immune response, as well as potential metabolic-related mediators to explain the observed associations between diet and immune response through mediation analysis in the ALSPAC study.
B4541 - Investigating the associations between ADHD sleep disturbance and comorbid mental health outcomes across the lifespan - 04/03/2024
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common diagnosis. It affects around 3% of the population. ADHD has symptoms of hyperactivity, inattention, or both. Although ADHD is usually seen in childhood, it is now accepted that for many, ADHD persists into adulthood. Adults with ADHD are more likely to also have symptoms of depression and anxiety. Without effective management, this can make life more difficult for someone with ADHD.
Both children and adults with ADHD also often report sleep problems. Getting good quality sleep is crucial to someone's health. Sleep problems are also a key aspect of mental health conditions, including anxiety and depression. In this proposal, we set out how we aim to investigate what role sleep disturbance plays in both ADHD and mental health.
This project will use existing measures collected from consenting ALSPAC participants. In particular, we will use measures of ADHD symptoms, sleep, anxiety, and depression. Through statistical analysis, we will explore whether ADHD influences someone's sleep quality. We will build on this by exploring whether a relationship between ADHD and sleep goes on to impact someone's mental health.
Our findings may have consequences for how we view the importance of sleep for someone with ADHD. Crucially, sleep is a modifiable behaviour. Our results may help promote clinical recommendations that consider sleep as a key component of ADHD management.
B4537 - Rare and common genetic influences on cognitive and behavioural phenotypes in ALSPAC - 04/03/2024
Emma will be re-using the existing dataset from B3565, no additional data will be required for her student project.
Emma will study rare and common genetic influences on cognitive and behavioural phenotypes in particular, as measured by the Strengths and Difficulties questionnaire across childhood and adolescence. She will analyse exome sequencing and genotyping array data from ALSPAC as well as the Millennium Cohort Study. Her project aims to understand the contribution of genetic effects on cognitive development.
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.
B4536 - Growing up in turbulent times Wellbeing of adolescents in a longitudinal and cross-cultural perspective - 20/02/2024
Large scale societal crises, e.g. recessions, pandemics, can have long-lasting effects on health and wellbeing. This is particularly the case when experienced at important times in life, such as in adolescence. Adolescence (age 10-25) is a time when young people experience many changes in terms of biological, social and cognitive development. It is also a time when many important transitions are made. For instance, leaving the family home, leaving school and entering further or higher education and work, and forming partnerships and families. Therefore, experiencing societal crises during this life stage may be particularly challenging and disruptive.
This project will look at the impact that societal crises have on the lives of adolescents across Europe. We will use comparable longitudinal datasets to examine the impacts that the Post-Communist Transformation had on families in Eastern Europe, the impact of the Covid pandemic on adolescent transitions, and the effect of the Great Recession in 2008.
This work forms part of a large, cross-European project for which we are currently seeking funding. The project uses large longitudinal datasets from multiple countries. ALSPAC provides an important comparator cohort to the Czech ELSPAC study. The Czech cohort were born during the time of great upheaval during the Post-Communist Transformation of the early 1990s. At this time there was growing socioeconomic inequality. In contrast, the ALSPAC cohort were born into a society with wide, persistent socioeconomic inequality. By directly comparing these two cohorts we will be able to look at the consequences of the Post-Communist Transformation and more broadly, family socioeconomic inequalities, for family mental health, particularly the mental health and wellbeing of adolescents.
B4538 - Genome-Wide Association Study of Lipid Traits and the influence of Body-Mass Index and Age - 20/02/2024
The Global Lipids Genetics Consortium (GLGC) is a world-wide collaboration of investigators dedicated to understanding how the different variants in genes can influence the blood levels of lipid traits, such as cholesterol, triglycerides, etc. In our study, we will analyse the association of gene variants with blood lipid levels, considering the effect of age and body-mass index in ALSPAC participants. The results will be combined with results from other groups of participants around the world to be able to identify new gene variants that help understand the biology of blood lipid traits.
B4539 - How does physical activity and body composition effect the risk of fracture in adults aged 30-60 - 21/02/2024
Background
Broken bones cause pain, disability, and time out of work in adulthood. Most of what we currently know about the causes of broken bones comes from research on children, adolescents, and the elderly. Little is known about what contributes to the risk of broken bones in people through mid-life.
This project will focus on how different levels of physical activity and body composition, i.e. bone strength and weight, may change the risk of a broken bone in people from early adulthood to mid-life (age 30-60).
Your approach
I will use data collected from large groups of people over many years, including the UK Biobank and the Avon Longitudinal Study of Parents and Children. These data sets have measures of physical activity, obesity, bone fragility and individual genetic data, as well as information on the outcomes of broken bones in adults aged 30-60. I will use classic epidemiology techniques and recent genetically-informed approaches to better understand the complex relationships between physical activity, body composition and broken bones.
Expected impact
Better understanding of the causes of broken bones in middle-aged adults will enable early targeted preventative strategies and hope to reduce the burden of fractures in later life.