Cancer is a leading cause of death, responsible for one in six deaths worldwide. Of these, breast is most common cancer and the 5th leading cause of death among all cancers. Breast cancer can be categorised as a hormone-sensitive cancer, along with prostate, endometrial and ovarian cancer, meaning the development of these cancers is driven by hormones. Menopause marks the end of a woman’s reproductive life and is characterised by changes in a woman’s biology including in the levels of sex hormones circulating their body. The levels of these hormones have been implicated in the risk of these hormone-sensitive cancers. The amount and distribution of fat (adiposity) are also known to change across the menopausal transition and in addition are known major risk factors for cancer. What is not currently known is how the changes in hormones and fat, specifically due to the menopause, affect the risk of cancer. Both hormone levels and fat quantity and distribution are known to be regulated, to some extent, by genetics. This project aims to use genetics of changes in hormone levels and fat quantity and distribution to determine their causal role in cancer risk, both independently and through their interaction. This research will help to identify the causal role of risk factors for cancer at a specific time-point which could then be targeted to prevent cancer.

We and others have identified numerous factors that influence mental health in young adults and early adulthood. These include obstetric complications, adversity, cannabis use, population density, immigrant status (PMID: 29352556, 12091183, 31563981) and most recently exposure to COVID (PMID: 35987197). Additionally, in the ALSPAC cohort, we recently identified that suicidal ideation at age 17 is associated with 7-fold increased odds of psychotic disorder, and with depressive disorder and generalised anxiety disorder at age 24. Indeed, over 40% of those with psychotic disorder in early adulthood had experienced this symptom in late adolescence (Mongan et al, 2022, unpublished).

We and others have also identified evidence for inflammatory marker dysregulation both preceding and in association with psychiatric disorders including psychosis, depression and recently, long COVID (PMID: 36085284 , 35472304). Dysregulation of acute inflammatory markers [such as Interleukin (IL)-6 and C-Reactive Protein] and complement proteins has been reported prior to and in association with these outcomes (PMID: 25133871, PMID: 32857162). Using ALSPAC data we identified for the first time the cross-sectional association of suPAR (soluble urokinase plasminogen activator receptor- an established marker of chronic inflammation) and IL-6 (an established marker of primarily acute inflammation) with psychotic disorder in young adults (Mongan et al 2022, under review). We previously found an inverse association between the anti-inflammatory marker n-3 fatty acid docosahexaenoic acid (DHA) at age 17 and psychotic disorder at age 24 in the ALSPAC cohort (PMID 34059620). Using ALSPAC data we have also shown for the first time that elevated suPAR is associated cross-sectionally with cannabis exposure, itself a marker for mental ill-health (Power et al 2022 (under review)).

We now seek to expand our knowledge to mental health outcomes in early adulthood (at age 24 and also at age 30 (when available)). We wish to examine not only associations between risk factors and inflammation in relation to clinical thresholds of psychiatric disorders, but also in relation to specific symptoms and symptom severity.

We hypothesise that exposure to environmental risk factors and early-life adversity is associated with chronic inflammatory dysregulation, in line with recent evidence (PMID: 31682707, 26033244, 34990745). We also hypothesise that inflammatory dysregulation will be more common in those who go on to report mental disorders in adulthood (PMID: 25133871, PMID: 32857162). Crucially, we hypothesise that inflammatory dysregulation mediates the relationship between environmental exposures and adult mental disorders, which could provide evidence for a biological mechanism by which environmental exposures influences the risk of adult mental disorder. Alternatively, environmental exposures and biological risk factors may operate independently, but have a cumulative effect on the risk of mental disorders.

We propose to investigate this using a combination of existing ALSPAC data, and new data derived from assays undertaken by us which assessed levels of the robust marker of chronic inflammation, suPAR, in age 24 plasma samples donated by ALSPAC participants.

Daily movement behaviours can be broadly classified into four categories, dependent largely on intensity, namely sleep, sedentary behaviour, light physical activity and moderate-to-vigorous physical activity. The government recommend children and young people partake in an average of 60 minutes of moderate to vigorous physical activity every day, in order to maintain good health. Whilst current research supports the need to improve physical activity engagement in childhood, interventions thus far have shown little to no significant improvement. Furthermore, whilst it is suggested that children with asthma follow the same guidelines in regard to engagement in physical activities, but no guidance is given as to the type of exercise, or whether different intensities are more suitable for different clinical groups.

The aim of this project is to characterise the composition, and level of, physical activity behaviours throughout the day, with specific interest in exploring whether those diagnosed with asthma show similar patterns to those without asthma. The data set will be combined with data from the Millennium Cohort Study and the Commando Joes/X4A Trial, and analysis will consider age, sex and asthma status.

This project will investigate the role of the social and physical environment in the development of internalising problems (i.e., anxiety and depression) in autistic young people (AYP), thereby contributing new insights to inform prevention and treatment. Internalising problems are common in autistic people, with a lifetime prevalence around four times that of non-autistic people. They typically arise by adolescence, persist across the lifespan and have substantial negative effects on wellbeing, functioning, physical health and mortality. The need for work that informs care for internalising problems has been highlighted by the autism community as their top priority for autism research. This reflects the fact that evidence-based interventions for autistic internalising problems are lacking because, currently, our understanding of how and why these difficulties develop and persist is limited. In particular, we lack understanding of how features of the social and physical environment influence the development of internalising problems of AYP.

Across the whole project, we take an ecological approach to understanding the development of internalizing problems in AYP. We seek to understand the development of mental health problems by modelling the dynamic interplay of environmental and personal factors and elucidating how diverse factors at different levels operate over time.

By enhancing understanding of autistic mental health, the study will help improve the wellbeing and life chances of autistic people by informing the development of interventions to treat and prevent their mental health problems. Our focus on environmental risk is especially likely to yield practical results, as it promises the identification of modifiable risk factors (e.g., parenting, peer victimisation, neighbourhood built environment) as putative targets for intervention.

This project aims to improve our understanding of which factors are predictive of mercury levels in pregnant women. Many factors have been reported in isolation, but little work has previously been done to compare them and identify their relative importance. Fish consumption is likely to be a primary source, but there may be a role of social factors (eg job) and genetic makeup.

This project will process the data that ALSPAC has collected from participants using CAMCOG (cogntive tests)

Puberty and adolescence is an important period in human development characterized by rapid transformations in anatomy, physiology, and behaviour, and the establishment of social and economic resources to maintain health and wellbeing across the life course. Despite the importance of puberty, little is known on the patterns of various developmental changes during puberty. Early life environmental exposures and socioeconomic position are thought to influence later health but whether they influence pubertal development is unclear. This study will describe the timing of different markers of pubertal development in 3 cohorts from the UK, USA, and Denmark, and examine early life environmental and socioeconomic influence on the timing of puberty.

We plan to identify genetic markers across the genome for subtypes of childhood eczema across the course of disease. These phenotypes include "no eczema", early transient eczema", "late-onset eczema", "intermittent eczema" and "persistent eczema", which have been generated using information from 5 points in times throughout childhood. These time points include age 6 months to 1 year; 2-3 years; 4-5 years; 8-10 years and 14-18 years of age. This study will help us understand the genetic and environmental factors that may differ between different disease subtypes, and will help inform the definition of eczema and how it is treated.

Physical abilities are complex traits that are influenced by both genetic and environmental factors. Genetic factors account for 20-80% of muscle strength, endurance capacity, speed, and flexibility. Physical abilities depend on motor coordination, which is defined as the dexterity to coordinate movements of multiple body parts. Well-developed coordination allows people to control their body parts in space and time quickly, efficiently, and accurately; so-called "good motor skills”. Motor coordination was commonly thought to be more influenced by environmental factors. However, recent twin studies have shown the heritability of motor coordination, suggesting the involvement of genetic factors in “good motor skills”.

Recently, we have demonstrated the heritability of “motor skills” by selective breeding in mice for good and poor coordination. Our comprehensive genomic and gene functional analyses in these mouse lines also identified candidate genes responsible for “good motor skills” in the cerebellum and cerebral cortex. The goal of this study is to determine whether the candidate genes for “good motor skills” identified by animal studies are involved in human motor coordination. To reach our goal, we investigated the association of SNPs in 11 candidate genes with children’s motor coordination using ALSPAC data.