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.

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.

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).

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.

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.

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.

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.

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.

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.