Proposal summaries
B4375 - Heart rate variability and arterial stiffness in young adults with and without type 1 diabetes - 18/07/2023
Individuals with childhood-onset type 1 diabetes (T1D) have a life expectancy 17 years lower than that of their healthy peers, with over 2/3 of this increased risk of premature mortality due to the development of cardiovascular disease. A significant proportion of young people with T1D have evidence of cardiovascular risk factors which are already detectable by adolescence / young adulthood; including well-established markers of future heart attacks and other events such as nervous system problems (autonomic dysfuntion), high blood pressure (hypertension), and stiffening of the major arteries (early vascular ageing).
B4376 - Ideal cardiovascular health and the development of vascular disease in the young - 18/07/2023
In 2010, the American Heart Association (AHA) created ‘Life’s Simple 7 (LS7)’ – a risk score aimed at quantifying ideal cardiovascular health behaviours within large populations. This risk score consisted of seven modifiable factors known to influence cardiovascular disease; namely body weight, physical activity, diet, smoking, total cholesterol, glucose, and blood pressure. Over the last 12 years, LS7 has been shown to be effective in predicting a wide-range of future cardiovascular events in older cohorts, as well as the subclinical development of early cardiovascular risk in the young. In 2022, the AHA revised and updated this risk score to become ‘Life’s Essential 8 (LE8)’, adding sleep quality as a new modifiable risk factor for disease and altering definitions of what constitutes ‘ideal behaviours’ in many of the other risk factors. The comparability of this new score to LS7, however, and feasibility of using it in large population datasets to predict outcomes such as early changes in heart and brain health remains unknown.
B4379 - Heatwaves wellbeing questionnaires to inform adaptation - 22/08/2023
This is part of a work package is Eunice Lo's fellowship proposal to the Royal Society. It will investigate the wellbeing effect of heat on humans, because wellbeing is difficult to model due to a lack of long-term data.
B4378 - Developing and piloting heat wave questionnaires in ALSPAC - 08/08/2023
Extreme heat (> 40°C heat) is becoming more and more commonplace in the UK meanging overheating in homes and buildings is a key risk. It is important to understand how this affects people’s physical and mental health, wellbeing and behaviour during heatwaves so that strategies can be developed to help people adapt.
Most research in the UK related to heat and health is focused on outdoor temperatures and population-scale health outcomes (e.g., mortality in South-West England) rather than people’s experiences and perceptions of heat, which varies between individuals and the buildings they live in.
We will fill these gaps by working with ALSPAC to develop and test a questionnaire that will ask participants about their experience and behaviour during a heatwave. The data collected from this plot will not be linked back to any ofther data but will help us to understand how heat might affect the health and wellbeing ofdifferent people, help to inform the development of early warnings and contribute to a fellowship application leading to more detailed research in ALSPAC.
B4345 - Maternal serum cardiometabolic biomarkers in pregnancy with offspring cardiovascular health - 18/07/2023
The association between maternal cardiometabolic markers and offspring cardiometabolic health has remained elusive. Barker et al. have postulated that the intrauterine environment and early-life development serve as potentially important determinants of cardiovascular disease (CVD) later in life. However, previous studies were constrained by limitations such as small sample sizes, short durations of follow-up, or inadequate control for confounding variables. Consequently, a systematic investigation of maternal gestational cardiometabolic biomarkers and their relationship with offspring cardiometabolic health in a large-scale cohort is warranted.
B4368 - Using large cohort studies to identify scar-associated genetic variants for mechanistic testing in mouse and zebrafish models of - 03/07/2023
Repair of adult tissues involves a complex interplay of several key cell lineages and inevitably leads to formation of a fibrotic collagenous scar, whereas embryonic tissues heal perfectly without any resulting scar deposition. This dramatic difference in repair efficiency between embryonic versus neonatal/adult tissues has been instrumental is guiding us towards potential causes of scarring. Indeed, we now believe that one major driver of scarring is the wound inflammatory response which doesn't initiate until a transition period in fetal development which, in turn, coincides with the developmental onset of tissue scarring. This insight has led us towards further mechanistic cell and molecular studies in model organisms, such as mouse and zebrafish, which help us better understand the scarring process and how one might modulate the wound inflammatory response in order to improve or prevent scarring.
Whilst these approaches, motivated by comparing embryonic versus adult healing, have been fruitful, it is clear that scarring is a complex, multifactorial response likely driven by a number of interacting mechanisms. We would like to use a conceptually similar comparative approach to gain further insights into the fundamental cell and molecular mechanisms of scarring by analyzing differences in degree of scarring, not between embryo and adult, but rather across human adult populations since we know there is a range of “scarring phenotypes” from “minimal scarrer” to keloid scarring individuals. This use of human phenotypic variation in a population based, genetic association approach (genomewide association studies – GWAS), has the potential not only to yield gene variant correlates of scarring, but also to point towards specific biological contributions to wound healing. The use of natural human experiments (e.g. Bacillus Calmette–Guérin (BCG) vaccination wound healing, Caesarean section (C-section) wound scarring and examples of human disease related fibroses) has never before been used for identification of scarring genes, even though the approach has proven to be powerful for discovering genes associated elsewhere with a wide variety of complex health outcomes (www.ebi.ac.uk/gwas/). Furthermore, alongside a growing number of catalogues charting the results of human genetic association studies for health outcomes and intermediates there are tools able to consider (in frameworks of causal analysis) the existence of potentially causal and modifiable relationships between exposures of interest (e.g. inflammation, differential wound repair or scar) and health outcomes (e.g. wound healing, recovery, and disease).
Using human genetic data to help explore the potential of biological pathways contributing to health and disease in applied epidemiological designs is an approach that we have refined and developed and is an integrated approach to health research that has yielded important clinically relevant insights, but has also indicated opportunities (e.g. associated signaling pathways for targeting) to unify basic science approaches with human population based health data (see below).
B4364 - The genetics of learning difficulties and related outcomes - 14/07/2023
Dyslexia is a common and highly heritable conditions. New sequencing technologies allow us to identify potential mutations that might increase the risk of developing dyslexia. This project aims to identify such mutations and access whether they might contribute to dyslexia specifically or other related cognitive traits, e.g. language or mathematical abilities. We will conduct our analysis in clinical cohorts enriched for dyslexia cases and will follow the top results in the ALSPAC cohort to validate and better interpret our results.
B4363 - Longitudinal mental health outcomes for people with childhood eye disease - 28/06/2023
Children with squint may be more likely to have depression in their teenage years. We do not know why this happens but think it could be:-
-because children with squint are treated differently by others, or
-because children with squint are different to others in some way (for example, they may be more likely to have autism).
A sample of 7,825 children taking part in the ALSPAC study had their eyes tested for squint when they were 7 years old. In addition, the participants have completed a variety of tests for depression throughout their adolescent, and young-adult lives.
Our study is going to use these data to:
a) Find out if childhood squint is associated with adolescent mental health conditions.
b) Explore other associations with squint and identify possible causes of the association.
We will do this by looking at all the children who had their eyes tested at age 7 years and compare the adolescent depression scores of those that had squint to those that did not.
B4360 - Co-occurrence of homelessness and autism in a population based cohort - 28/06/2023
There is emerging evidence of high levels of (often undiagnosed) autism within homeless populations, with current estimates of around 12-18% of people receiving support for homelessness meeting criteria for an autism diagnosis. However there is a lack of population-wide studies exploring the co-occurrence of homelessness or insecure housing and autism diagnosis or traits.
B4341 - Lifelong understanding of cerebrovascular health - 26/07/2023
Currently, vascular ill-health appears to be the most preventable component of cognitive decline in older age. There is however very limited understanding about the time at which signs of damage are already present in diseases that take decades to result in symptoms. In this project we will work to identify through imaging the markers that can help us quantify the health status of vessels and associated tissues in the brain. We will also work to better understand their relationship to known risk factors for cardiovascular disease.
B4362 - Metabolomic associations with liver enzymes and fatty liver disease - 28/06/2023
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains poorly understood. Investigation of circulating metabolites may help in elucidating underlying mechanisms and identify new biomarkers for NAFLD. In this meta-analysis we will examine the association between plasma metabolites and NAFLD as well as liver enzymes using data from four CHARGE cohorts (Rotterdam Study – RS, Avon Longitudinal Study of Parents and Children – ALSPAC, Study of Latinos – SOL, Insulin Resistance Atherosclerosis Family Study – IRASFS).
B4292 - The Impact of Environmental Adversity on the Brain Identifying Biomarkers and Modifiers of Environmental Risk in Psychosis - 31/07/2023
Experiencing environmental adversity is associated with a greater likelihood of developing a mental health disorder. There is a need to identify biomarkers that predict the emergence of poor mental health outcomes following environmental adversity, as the targeted removal of these risk factors could reduce the rates of mental illness by up to a third. Understanding which environmental risk factors impact brain structure and function, and the identification of protective factors, could be the key to preventive medicine approaches. This current proposal would acquire magnetic resonance imaging (MRI) scans in the Avon Longitudinal Study of Parents and Children Generation 2 study (ALSPAC-G2). We are applying for funding from the Wellcome and MRC Career Development Awards.
As ALSPAC-G1 participants are now entering child-bearing age, this presents a unique opportunity to study their offspring (currently n=1875 and growing) to examine inter-generational determinants of mental health. The proposed project uses an accelerated longitudinal design, and would obtain MRI scans in 200 children aged between 5 and 15, who would be followed up and rescanned after 2 years. This project would examine trajectories of brain structure and function during critical periods of neurodevelopment, at a time when most mental disorders first occur.
B4367 - ALSPAC longitudinal metabolomic data collection - 14/07/2023
Whilst other studies exist elsewhere charting the metabolome of disease or of adult or mid-to-late age participants, there are few examples of longitudinal metabolomic data. ALSPAC does have proton nuclear magnetic resonance spectroscopy data on an extended lipidome and select protein panel (Nightingale), however data do not exist for longitudinal liquid chromatography/mass-spectroscopy derived metabolites. This approach has the potential to substantially expand the metabolite collection in ALSPAC, to allow new association analyses and also to provide a benchmark or longitudinal standard for circulating metabolites across ages. This work proposes to collect new data (from existing samples) under a sampling framework aiming to maximise capture of longitudinal changes in metabolic profile.
B4357 - Longitudinal trajectories between sports participation and mental health in ADHD - 27/06/2023
Attention deficit hyperactivity disorder is a major neurodevelopmental disorder during childhood, affecting 5% of children across the UK. Mental health difficulties, such as anxiety, stress, and depression, often cooccur with ADHD and can persist from childhood, through adolescence, to adulthood. Separately, ADHD has also been linked to increased levels of obesity and a more sedentary lifestyle. This issue is concerning given that research has shown that participation in exercise and sports provides a range of health-related benefits, including better mental health. Hence, we aim to 1) explore the biological, social, and psychological factors that predict higher sports participation in individuals with ADHD, 2) evaluate whether higher sports participation predicts better mental health in the long-term in individuals with ADHD, and 3) explore whether the longitudinal relationship between sports participation and mental health to be different between individuals with higher and lower symptoms of ADHD.
B4366 - Child poverty early life adversities and adolescent health and education outcomes - 03/07/2023
4.2 million (29%) children in the UK lived in relative poverty in 2021-22. Similarly, adverse childhood experiences (ACEs), such as child maltreatment and parental mental health problems, are common in the UK. Child poverty and ACEs can have lifelong consequences for children. However, the extensive research undertaken to date on the effects of ACEs on lifelong health has largely ignored the role that child poverty plays, and vice versa. Consequently, the ways in which child poverty and ACEs are related to one another and, subsequently, to adolescent mental health and education outcomes, are not well understood. Partly, this is due to:
i) a lack of longitudinal studies which track the same people over time. Longitudinal studies enable us to investigate how child poverty and adversities relate to one another over time, how quickly a move into poverty affects different ACEs, and the importance of the timing and duration of early life experiences;
ii) a focus only on income-based poverty, when poverty is experienced by families as more than a lack of income;
iii) investigating a limited set of adversities (e.g. only child maltreatment), rather than taking a broader view of adversities to include parental mental health and domestic abuse, for example;
iv) assuming that all families experience child poverty and adversities similarly when we know that some families, e.g. those with more children or from ethnically minoritised groups, have higher risks of being driven into and remaining in poverty.
B4365 - Desistance from violent and non-violent crime - exploring pathways across space and time - 04/07/2023
Criminal behaviour peaks in mid- to late-adolescence,
and then declines throughout early adulthood. However, there are
individual differences in the course of criminal behaviour across this time period,
with a small proportion of young people continuing to commit crimes beyond the
peak age for criminal offending. Desistance is defined as “the process by which
criminality, or the individual risk for antisocial conduct, declines over the life course,
generally after adolescence”. Life-course theories of desistance, based on
high-income countries, suggest that ‘turning points’ (e.g., employment) may
encourage desistance from crime, whereas ‘snares’ (e.g., substance use) may
prohibit desistance. Given that nearly 90% of the world’s population live in low and
middle-income countries, and these countries (particularly in Latin America,
and Sub-Saharan Africa) have much higher rates of serious crime than high-income
countries, it is essential to establish whether the process and theories of
desistance are universal and replicable.
B4355 - The association between maternal and infant omega-3 fatty acid iron and vitamin D status and childhood obesity An ALSPAC study - 22/06/2023
This project aims to explore the direct and programming effect of maternal and infant consumption of three key nutrients (omega-3 fatty acids, iron, vitamin D) on subsequent indicators of childhood obesity. Dietary records and anthropometric/body composition data and genetic profiles from ALSPAC will be analysed to determine if there are any associations between maternal/infant omega-3 fatty acid, iron and/or vitamin D status and body composition measures, including weight, length/height, levels of adiposity and muscle mass. To investigate if these nutrients have an obesity programming effect, the dietary intake of pregnant women (in week 32 of pregnancy) will be analysed, along with the serum samples for the same nutrients to explore if the nutritional status has an effect on infant levels of obesity. To see if these nutrients influence levels of infant and childhood body composition, both short-term and longer term effects will be investigated (infant at age 4 months and child at age 36 months).
B4347 - Smoking behaviours and transitions to vaping in early adulthood - additional data collection - 22/06/2023
We will use data from ALSPAC to investigate predictors of trajectories of smoking behaviours, and transitions from smoking to vaping in early adulthood. Smoking remains the leading cause of preventable cancer; understanding factors associated with smoking and vaping, particularly during early adulthood (a critical period when transitions out of smoking are likely to begin), will inform future cancer prevention programmes and public health policy. This includes identifying predictors that can be used to tailor these programmes more effectively, as well as establishing causal risk factors where interventions could be targeted.
We are proposing to collect measures of smoking and vaping in the next questionnaire. This would enable us to extend existing work being carried out as part of B3499.
B4356 - Eating Disorders Delineating illness and recovery trajectories to inform personalised prevention and early intervention - 20/06/2023
Eating disorders are serious psychiatric conditions that often start in adolescence. Prevalence and burden of eating disorders are rising, they are developing at earlier ages and hospital admissions rising sharply. Currently, there is a lack in our understanding of how sociocultural factors (e.g., food insecurity, racial discrimination) interact with psychobiological factors (e.g., gender) and comorbidities (e.g., depression). This information is vital for informing prevention and early intervention methods for eating disorders in adolescents.
B4336 - Developmental origins of thyroid function regulation and its neurocognitive and reproductive consequences - 20/06/2023
Thyroid dysfunction due to hypo- or hyperthyroidism affects 200 million people worldwide and is a major health burden, particularly in women who are 4-10 times more likely to suffer from hypothyroidism as a result of autoimmune disease. Thyroid hormones are vital for healthy metabolism, tissue differentiation, neurodevelopment, growth, immune function, reproduction, and ageing, yet the relative contribution of environmental exposures (e.g. nutrition, psycho-socio-economic adversity, etc.) in shaping thyroid function regulation remains unknown. The thyroid axis is especially important for the health of women and their children, but currently there is a lack of intergenerational data that can help understand the complex interplay between iodine, environmental factors in early life and thyroid function regulation in the offspring. We aim to fill that gap by investigating (1) critical environmental exposures that impact thyroid function regulation, and their subsequent influence on (2) reproductive health and (3) neurocognitive outcomes. Within these analyses we will look at both natural variation in thyroid function parameters as well as pathological variation due to thyroid dysfunction. At the centre of this exploration is the complex interplay between mother and offspring around limited iodine resources and thyroid function regulation during pregnancy and its long-term consequences. Identifying critical periods of thyroid function plasticity may have significant implications for the optimal timing of comprehensive public health interventions that can decrease the burden of thyroid dysfunction and its health costs over the life course. This proposal has been adjusted from proposal B3905 submitted in 2021.