Proposal summaries
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.
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.
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.
B4527 - Inflammation and related metabolic and hormonal biomarkers for depression and other psychiatric conditions - 21/02/2024
What is the project about?
Immunometabolic dysfunction is implicated in depression and other psychiatric disorders, which may moderate the effect of antidepressant treatment. Existing case-control studies show changes in various blood immunometabolic biomarkers in depression, psychosis and other psychiatric disorders compared with controls, but longitudinal studies needed to assess temporality of association is scarce. Existing studies have almost exclusively used circulating blood biomarker levels as exposure which is informative, but does not reflect activity of the biomarker at cellular level accurately. Therefore, there is a need for developing novel measures reflecting biomarker activity/signalling more accurately to better understand the role of inflammation in psychiatric conditions.
My project will address these key issues using: i) longitudinal analysis testing the relationship of blood immunometabolic and related biomarkers with depression and other psychiatric outcomes; ii) develop and implement novel measures of activity/signalling of specific biomarkers (namely, interleukin 6 or IL-6, renin-angiotensin system or RAS) in analyses testing their associations with blood biomarkers and psychiatric outcomes.
Why is the project important?
Depression is a global public health concern, with recent research suggesting that it affects around 1 in 6 people in the UK. About 1 in 3 people with depression do not respond to currently available medications suggesting other mechanisms are involved. Demonstrating prospective associations of blood immunometabolic biomarkers with depression will strengthen causal inference and identify specific biomarkers for future investigation. Demonstrating how the activity of specific depression related biomarkers (e.g., IL-6 signalling) relates to depression risk will highlight specific pathways for intervention.
What do we know already?
While it is known that abnormal functioning of neurotransmitters such as serotonin are associated with depression, there is emerging evidence to suggest that inflammation may play a key role in its development. Studies have shown that individuals with major depressive disorder (MDD) have increased levels of interleukin 6 (IL-6) in the blood than healthy controls. Mendelian randomisation studies suggest a potential causal effect of IL-6 on depression and schizophrenia. However, which particular IL-6 signalling pathway underlies these associations remain unclear.
B4525 - Maternal health and offpsrings bone health - 26/02/2024
Osteoporosis is a condition that causes bones to become fragile and more likely to fracture, even as a results of a minor bump or accident. The amount of bone accumulated from birth to young adulthood is the most important predictor of osteoporosis. Several factors influence the accrual of bone mineral during childhood and adolescence, including heredity, diet, physical activity, and endocrine status. It is postulated that risk of poor bone health may be programmed as early as in the intrauterine period. Maternal diet, exercise, and smoking, along with maternal health conditions like hypertension, diabetes, asthma, anaemia, and renal diseases, might affect fetal growth, development, and bone mineral acquisition. In vivo study showed that maternal glucose control of diabetic mother as can impact the skeletal growth and long-term bone health of their offspring.
The present study will be the first to assess the association between maternal diabetes, including pre-existing and gestational diabetes, and offspring’s bone health. Our study will provide compelling evidence as to whether maternal diabetes is associated with measures of bone health in children and young adolescence.
B4521 - Investigating the associations between asthma and anxiety/depression - 12/02/2024
Asthma is the most common long-term condition among children and young people in the UK, with over one million children currently receiving treatment for it.
People with asthma often experience anxiety and depression. We do not fully understand the link between all these conditions. We also don’t know if the relationship between them is causal (having one condition causes the other to develop).
Project aims
We want to identify whether there is a link between asthma and mental health disorders. We will do this by using data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
ALSPAC is an ongoing study looking at the health of children born to mothers living in a specific part of England in the 90s. The original study has since expanded to include the next generation of children and their families.
We will use the large volume of data available through ALSPAC to explore the links between being diagnosed with asthma as a child and the likelihood of developing anxiety and depression. We will also look at the reverse, ie. whether having anxiety and depression as a child increases your likelihood of later being diagnosed with asthma.
What we hope to achieve
Findings from this study could support the development of clinical trials targeting patients with asthma and anxiety/depression. In turn, this could improve how people living with asthma manage their condition, reduce the number of exacerbations they experience and decrease the number of times they admitted into hospital.
This research is part of a PhD project and is being led by Dr George Nava. It is a collaboration between the respiratory and mental health themes of the Bristol BRC.
B4534 - Measurement Invariance in predictors of dropout from cohort studies - 12/02/2024
Individuals who take part in voluntary studies provide valuable data for health scientists across a range of health-related outcomes. These studies are extremely useful for understanding relationships between health related exposures and health outcomes. Results from studies such as ALSPAC (Children of the 90s) often rely on statistical methods to apply such relationships to the wider population (as the people who take part in these studies are often unusual in some way). One of the most commonly used statistical methods for this is called weighting, where we statistically "up-weight" people who are less likely to take part in a study, and "down-weight" people who are more likely to take part in a study, so that we can apply our findings to populations which are dissimilar to the studied (ALSPAC) population. It is not well understood how these methods perform in cases where the weights are constructed from a complex measure such as mental health - which may be measured differently for people who remain in a study, and those who go on to drop out. This study will provide valuable insights into how we might approach this.
B4528 - Associations between mother-child interaction in infancy and depressive symptoms in adolescence - 13/02/2024
Mother-child interaction is an essential element in a child's development that is impacting children’s emotional and psychological well-being. This aspect of early relational dynamics is especially critical in understanding the development of depressive symptoms during adolescence. Despite its significance, current research on how early mother-child interactions influence the development of depressive symptoms in adolescents, particularly using longitudinal data, remains limited. Given the existing literature, a more nuanced exploration into how these early interactions shape mental health outcomes in adolescents is not only necessary but could be instrumental in developing early intervention strategies. Such interventions could potentially mitigate the development of depressive symptoms, thus contributing to healthier adolescent mental health.
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.
B4529 - Health effects of diet in young children - 06/02/2024
What young children eat can affect their well-being in many ways, and the wide range of food choices and the rising cost of food can make it difficult for parents and carers to choose the best options for their children. The aim of this project is to find out how young children’s diet affects their growth and health as they develop into adults. For example, are children who have more sugary snacks and drinks more likely to be affected by tooth decay or overweight and high blood pressure later in life? Do children who follow a mostly plant-based diet get the right amount of nutrients such as protein for ideal growth? These questions come from a recent UK government review of the gaps in our knowledge on young children’s diets. We will discuss these questions with parents to find out what else they would like us to find out about feeding their children well.
To answer the questions raised we will use information on the diets of pre-school children from two up-to-date national surveys. The National Diet and Nutrition Survey (NDNS) collects information on all foods and drinks consumed over two days as well as the height and weight of children across the UK. Around 1,200 1-5 year-olds are expected to take part between 2019 and 2025. In addition, in 2024 the survey of Diet in Scotland’s children (DISH) will collect information on what around 300 children aged 2-5 years eat and drink and some further questions about their general food habits and household food situation. These surveys will tell us how different types of diets and food choices can provide enough nutrients for health and growth.
To find out how diet in young children affects longer-term growth and health we will use information from the Avon Longitudinal Study of Parents and Children (ALSPAC), a Bristol-based study of 14,000 children born in 1991-2 and their parents who contributed information on the children’s diet and health regularly over the last 30 years. This study will allow us to look at how diet in children under five is related to dental, heart, and lung health when they become young adults. By comparing the diet of young children in ALSPAC with the diet of children in the NDNS and DISH surveys we will be able to assess the changes in children’s diet across the last 30 years.
Studies from around the world have suggested that young children’s diets affect their health throughout their life. This project is designed to provide insights into the importance of these issues in the UK. This will help those who design the programmes and guidance which support all parents and carers to feed their children well.
B4526 - THE PLACENTA IN MATERNAL AND FETAL CARDIOVASCULAR HEALTH AND DISEASE - 12/02/2024
The placenta is the crucial interface between mother and developing fetus during pregnancy, enabling exchange of nutrients, oxygen, and waste products. The placenta is essential for a healthy pregnancy; placental pathologies underlie some of the most common pregnancy complications, referred to as placental syndromes (PS). PS include hypertensive disorders of pregnancy (preeclampsia and gestational hypertension), fetal growth restriction, and preterm delivery, which are leading causes of maternal and neonatal mortality and morbidity. PS are associated with adverse cardiovascular health beyond delivery and throughout life, both in the mother and offspring. Yet the placenta remain understudied and the mechanisms linking PS, congenital heart disease in offspring and cardiovascular health in both mothers and offspring are not well understood. In this project we aim to understand the the basis for primary placental disorders as the cause of secondary heart and vascular disease, both in the offspring and in the mother.