Acute lymphoblastic leukaemia (ALL) is the most common cancer in children. Whilst a range of genetic abnormalities have been identified as crucial in disease initiation, these abnormalities alone are not sufficient for transformation. Maternal exposures during pregnancy such as smoking, or folate intake have the potential to impact on offspring DNA methylation. This epigenetic mark has also been shown to be altered in ALL. We have previously identified 5 CpG sites that have altered DNA methylation due to maternal smoking and folate intake and we aim to identify whether changes to DNA methylation at these sites affects risk of ALL.

Children born with the ability of self-regulated cues of hunger and satiety. During early life, this ability is developed in a good way will facilitate healthy eating behaviours, which may be associated appropriate weight gain. In the first two years, milk feeding and complementary feeding are main feeding aspects，which could have impact on children’s self-regulation of hunger and satiety cues. Previous studies showed that breastfeeding duration and timing of solid food introduction were associated with children’s eating behaviours(eg. enjoyment of food, food fussiness, picky eating, eating slowly, overeating and so on) and weight growth. For example, Samantha L. Rogers found that breastfeeding duration was related to slower weight gain during 1 to 6 month and 1 to 12 month, and that breastfeeding duration was associated with slowness in eating at 12 m. Wang jing found that introducing complementary foods before 4 months of age compared to at 4~6 months was associated with and increased risk of being overweight and obesity during children. These findings indicated that infant feeding practice may exert an important role on development of children’s weight health However, the evidence about the relationship between concrete feeding mode such as bottle feeding, breast feeding, feeding on demand and children’s eating behaviors and weight growth were limited. Whether children’s eating behaviors and related gene variant play a mediated role on the relationship between feeding practices and weight gain also deserves exploring from a longitudinal perspective.

The proposed study aims to identify biomarkers (DNA methylation and measures of health) of stress and early-life adversity that indicate risk and resilience for health, and the potential mitigation of health risks by family-related social factors. We want to explore this within the child, and investigate the possible intergenerational transmission of maternal experience to child health.

The coronavirus (COVID-19) pandemic has had and will continue to have an unprecedented effect of daily living for the foreseeable future. Aside from the obvious effects of COVID-19 on physical health, this pandemic is also likely to have a profound effect on mental health. The knock on effects on mental health could be far reaching and long term especially if not understood and managed.

In addition, it is likely to exacerbate existing inequalities and the costs are likely to be felt disproportionately to the already most vulnerable ( those with a history of mental illness, job and housing insecurity , poor neighbourhoods , single parents and those in abusive relationships).

A number of rapid surveys have indicated an initial perceived rise in depression and anxiety symptoms. However, without pre-pandemic information, an accurate indication of the change is not possible. This is essential for modelling projected risk which needs to be taken into account when planning further policy regarding social distancing and lock down enforcements.

Longitudinal data is thus crucial. It is also important to identify at risk groups who could benefit from immediate help and planning for currently unknown policies for recovery stages. This project will use the unique data hosted by ALSPAC to examine how and why mental health changes as a result of the public health policies adopted during the COVID-19 pandemic.

Alcohol is the leading cause of ill-health in young adults in the UK and Europe and is the fifth leading cause across all ages in the UK population and is estimated to be the seventh leading cause globally . There are over 1 million alcohol related hospital admissions and nearly 25,000 alcohol related deaths a year in England with trends, in stark comparison to other major causes of death, not yet decreasing.

Since our previous grant (ALSPAC Alcohol at 24) there have been several important changes to our understanding of the risks of alcohol, patterns of drinking in the population, and UK response to preventing alcohol related harms.

First, levels of drinking reported by adolescents in UK and many other countries have fallen, corresponding with a fall in alcohol related hospital admissions in those under 18, but not yet resulting in any measurable decline in alcohol related harms in young adults . The motivation, reasons (and potential modifiable factors) causing the decline are not yet known but under investigation. In adults in the UK there is some evidence that changes in alcohol use has been differential with greater reductions in low level drinkers and no change in heavier drinkers with subsequently little overall impact on alcohol related harms. At the same time harmful alcohol use has been recognised as an important contributor to the “deaths of despair” that have reduced life expectancy – especially among poorer and more marginal populations - in North America.

Second, in large well powered genetic studies (and against decades of observational data) the cardio-protective effect of alcohol has been shown to be false – and instead likely to be due to non-causal factors all along (such as confounding, selection bias and reverse causation). This implies that there is no compensation of low levels of alcohol use improving morbidity and mortality and no absolutely “safe” or “non-risky” levels of drinking – and clear benefits from reducing average consumption. The UK in line with other countries issued new guidelines on safe drinking levels – which are now the same for men and women – though evidence is unclear whether there have been any changes in the UK population as a result of the new guidance. Policy changes also are underway – notably in Scotland - based on economic models that show how introducing and raising minimum price of alcohol can reduce future alcohol related morbidity and mortality. [There have been other advances in use of MR and genetic markers to identify new targets for drug discovery, compare the impact of interventions, and test for interactions between behavioural exposures – but in European populations MR of alcohol use and AUD have been limited by lack of robust markers.]

Third, it is argued that alcohol related health harms may be under-estimated in part because cohort studies under-represent heavier drinking marginal populations but also because of an under-appreciation of the interaction of alcohol with other exposures. The burden of alcohol is greater in poorer communities, alcohol combines with other exposures to increase risk of liver disease, and alcohol can act as a “snare” increasing the persistence and halting the resolution of antisocial behaviour. This has led to a renewed focus on understanding how adverse alcohol trajectories develop and interact with other exposures to increase health and social harms to strengthen the evidence base ultimately for policy-makers but also for alcohol policy models that can show the impact of alternative prevention strategies.

Cardiovascular disease remains a major cause of ill-health and death. Maximum aerobic capacity (VO2p), a measure of circulatory capacity, is a strong predictor of future cardiovascular (CV) disease and general health. Most inter-individual differences in VO2p are established by age 30 and VO2p subsequently declines with age. The factors responsible for differences in peak circulatory capacity at maturity are not understood and we will identify them by studying participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort of over 15,000 individuals who have undergone detailed studies since before birth. This study will provide a unique insight into the determinants of peak circulatory capacity in adults and identify potentially modifiable factors for improvement of future cardiovascular health.

For the last 20 years the effects of bilingualism have been extensively studied in experimental psychology. Despite numerous well-designed studies and meta-analysis there is no consensus whether or not there are executive functioning benefits in those who speak more than one language. Potentially small sample sizes and retrospective data collection are the cause of this.

The bilingual advantage is embedded in the theory that bilinguals constantly inhibit a non-target language when speaking; strengthening a non-specific cognitive domain inhibitory control mechanism resulting in benefits on tasks that require inhibition. By investigating cognition (in particular inhibitory control) throughout a child’s life alongside their exposure to a second language and other confounding variables we hope to finally gain consensus on whether bilingualism can affect cognition.

The bilingual advantage has been thought to have a protective effect over dementia and cognitive decline in older adults. By establishing that there is a bilingual advantage that could be protective of dementia has the potential to be a major public health advantage.

The aim of this project's initial phase is to determine the feasibility of batch converting existing 3D whole body scans data into a generic file type so that they can be readily analysed. This is to support the development of future funding bids to use the scan data to investigate genetic determinant of body shape and its cardiovascular consequences.