It is now well-established that an early timing of puberty is associated with a greater risk of depression in girls during adolescence, and there is evidence that this relationship is causal. Far fewer studies have examined whether pubertal timing is related to depression in boys and findings are inconsistent. Some studies have found that boys with an early puberty have a greater risk of depression in adolescence, whilst others have found that a later puberty confers a greater risk. Such inconsistency is often attributed to measurement difficulties in capturing pubertal development in boys. It is also unclear whether any effects of pubertal timing on depression in boys persist beyond adolescence.

This project aims to describe the ALSPAC data on religious and spiritual beliefs, as well as identify any potential sources of bias. One of these associations that is of particular interest is whether RSBB has an affect on participation in the study. This is because studies like ALSPAC rely entirely on continued participation for the study to work, meaning if there are unknown factors behind participant's likelihood of continuing with the study this may result in bias when using these variables in analyses.

Stress-related psychopathology (e.g. depression and anxiety) affects one in eight children in the UK. It is therefore crucial to identify modifiable protective factors that can promote mental health in young people. Physical activity is a promising target for the prevention of depression and anxiety. However, the extent to which it can reduce the burden of mental disorders in young people is not known. This is due to the breadth of environmental, social, and genetic factors that could explain the relationship between physical activity and psychopathology. Furthermore, it is unclear whether physical activity can promote resilience to psychopathology in children who are at higher risk by virtue of genetic liability or adversity. This project will apply cutting-edge causal inference methods, including G-methods, fixed-effects regression, mendelian randomisation, and twin designs, to test whether physical activity can promote resilience against the development of stress-related psychopathology, using data from large population-based cohorts of children from the UK, Netherlands, Norway, and Finland. By comparing results across different studies and analytical approaches, the project will strengthen causal inferences from observational data and minimise potential biases associated with each method. In turn, the results will allow us to draw more confident conclusions regarding whether interventions targeting physical activity could help to reduce the burden of mental health problems in young people.

Mental health disorders like depression and anxiety are common and have consequences on all aspects of health. Mental health disorders like depression have a complex aetiology comprised of genetic and environmental risk factors, but importantly these risk factors predict different longitudinal profiles of depression (i.e., those with persistent depressive symptoms across adolescence compared to those who experience early adult onset depressive symptoms compared to those who experience low symptoms; Kwong et al., 2019 - JAMA Network Open). We have also shown that these depression profiles are associated with poorer downstream consequences like lower educational attainment and NEET status (Lopez-Lopez et al., 2019).

However, these studies are subject to measurement error and potential biases in recall which can weaken evidence. In order to identify the mechanisms underpinning poorer mental health and design appropriate interventions and preventions, it is important to understand the processes of mental health in granular detail. Ecological momentary assessment (EMA) provides one alternative design to address these biases and provides in depth information on mental health in real time via multiple assessments per day or per week over a given period of time. Crucially, EMA of mental health can be paired with other forms of data collection such as sleep, exercise and diet to examine relationships between mental health and wellbeing.

The purpose of this project is to conduct a small scale feasibility study to examine how EMA studies could be collected in ALSPAC and in particular, if they can be collected in individuals from different depression profiles. The results from this study would provide initial results that would inform how to run a large scale study in subsequent work.

This project aims to investigate the effect of parental stress on children’s development of non-cognitive skills and both emotional and behavioural disorders. In particular, we plan to investigate parental stress in the forms of: (a) maternal exposure to stressors during pregnancy; and (b) COVID-19 related health and financial stress during the height of the pandemic. This project will employ rich longitudinal datasets and use questionnaire data to examine parenting styles as well as epigenetic, genetic, and clinical biomarkers to examine the potential pathways of parental stress on children’s developmental outcomes.

Exploration of ethnic differences in DNA methylation patterns show that differences in methylation are largely driven by differences in cell composition of the blood samples methylation is measured from. This raises important questions about when and how differences in cell composition arise. One possibility is that they occur in response to early life infection and persist through life. This project investigates the potential link between early life infection (using H. pylori infection as a marker) and variation in cellular composition of blood samples collected at the same study timepoints.

We are investigating whether a mother's religious beliefs are related to their child's mental health.

Evidence suggests that alcohol use has different impacts on cardiovascular risk in females and males but results are somewhat conflicting. Few studies to date have examined sex differences in the association of alcohol use with risk factors earlier in the life course (for instance during early adulthood) and to our knowledge no studies to date have examined sex differences in associations of alcohol use with key molecular cardiometabolic traits that are known causes of cardiovascular disease.

Present in nearly all types of human cells, mitochondria generate the majority of our cellular energy and are thus often referred to as the ‘powerhouse of the cell’. In addition, mitochondria play important roles in signalling between cells and cell death (known as apoptosis). Although most of our DNA is within the nucleus (the ‘nuclear genome’ or nDNA), mitochondria contain their own DNA (the ‘mitochondrial genome’ or mtDNA), and human health is dependent upon the coordination of the products of these two genomes.

Genetic variants within mtDNA can cause disease (1) and are also linked to a growing number of age-related complex diseases (2), particularly neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, schizophrenia and multiple sclerosis (3). In addition, there are examples where the progression or severity of mtDNA disease is modulated by nDNA variants (e.g. LHON (4, 5)). Conversely, there is evidence in complex diseases where nuclear susceptibility factors are implicated, that common, inherited, mtDNA variation can influence traits such the age of onset (e.g. Alzheimer’s disease (6) and cardiomyopathy (7)).

More recently, the development of mitochondrial replacement therapy, a technique designed to avoid transmission of defective mitochondria from parents to offspring, sparked discussions on mitochondrial nuclear incompatibilities that would require matching donor and recipient mitochondrial and nuclear backgrounds, and more generally on whether the genetic makeup of healthy individuals reflects such incompatibilities (8).

This raises the question whether specific variant combinations of nuclear and mitochondrial alleles are depleted or enriched in the general population. This can be assessed by comparing their frequencies with the frequencies expected from the frequencies of the corresponding nuclear and the mitochondrial alleles assuming independent segregation. Such associations between variants can reflect mixing of different populations or selection against or in favour of particular variant combinations. Associations between nuclear and mitochondrial variants have been repeatedly reported (9, 10). However, it is unclear to what extent the observations reflect population stratification. This is of particular interest because mitochondrial genetic variants have been extensively used to track migration of populations and ancestry.

The aim of this study is to use the ALSPAC cohort genotyping data to: 1) identify combinations of mitochondrial and nuclear variants that are over or underrepresented in a well-characterised population, 2) ascertain whether under or over representation can be explained by heterogeneity within the population and 3) assess the effects of factors such as age or sex. The results will also provide a reference for studying the role of such combinations in human disease.