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.

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).

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.

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).

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.

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.

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.

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.