Developing good self-regulation skills is one of the most important tasks for a child to accomplish. Earliest signs of difficulties in self-regulation include excessive crying, sleeping, or feeding difficulties, which are labelled as ‘regulatory problems’. Increasing evidence has shown that regulatory problems in infancy/toddlerhood increase the risk of several negative outcomes such as attention problems, emotional and behavioral dysregulation in childhood, and depressive symptoms in adolescence. However, it remains unknown if regulatory problems in infancy/toddlerhood are also associated with adverse health and social outcomes in adolescence.

The current study aims to investigate whether regulatory problems in infancy/toddlerhood increase the risk of following adverse a) health outcomes in adolescence: harmful drinking, smoking, cannabis use, illicit drug use, problem gambling, unwanted pregnancy, obesity, excessive screen time, and self-harm at 18 years, and b) social outcomes in adolescence: getting into trouble with police, not being in education, employment or training (NEET), low peer social support, low closeness in romantic relationships and relationship with parents.

Multimorbidity (MM) happens when two or more different diseases are present at the same time in an individual. This is common between physical and psychiatric diseases with almost half of people with a psychiatric disease also having a physical disease. As well as about a third of people with a physical disease also having a psychiatric disease. These patients have worse quality of life than those with a single disease, they often struggle to get the best care and are at risk of living less long. A common and serious type of MM is between internalizing diseases (depression and anxiety) and cardiovascular disease (ICV-MM). Still, very little is understood as to how ICV-MM develops and why it happens. We do know however that both internalizing disease and cardiovascular risk (e.g., obesity, cholesterol) tend to begin before adulthood.

To really understand how ICV risk develops, we need large studies of people of all ages whose health has been followed over time. Studies of children are crucial because they can tell us about early risks for development of ICV-MM later in life. This is important for developing better plans to prevent at-risk children developing ICV-MM. We also know that certain conditions that start early in life (neurodevelopmental conditions) such as intellectual disability, autism and ADHD increase risk of developing ICV MM later. Children's environments can also increase this risk, for example, stressful experiences such as poverty and physical or sexual abuse. But how exactly neurodevelopmental conditions and early environmental risks influence the development of ICV-MM over the lifespan is still not understood. Certain groups are known to be at increased risk of ICV-MM, such as people of South Asian heritage and women, but we don't know why this is. Better understanding of how ICV-MM develops in different groups in society will help doctors give patients care that is matched to their specific needs. It will also help doctors, governments and schools prevent ICV-MM in at-risk children in ways that work best for them.

To really understand the complexities of ICV-MM development, a team of researchers with a wide range of expertise is needed who together understand physical and psychiatric diseases as well as how neurodevelopmental conditions and the environments people live in influence them throughout their lives. The PhD student will benefit from working within our LIfespaN multimorbidity research Collaborative (LINC), which combines wide-ranging medical and research expertise in physical and psychiatric diseases. LINC has brought together five very large studies (of which the student will access two – ALSPAC and UK Biobank) in which the health of many people has been followed over time. Rich medical data is available, including from medical records. Important information has been collected such as on people's living environments, life events and lifestyles. These studies follow the health over time of children, adolescents and adults. We can therefore study how internalizing and cardiovascular disease happen together in adulthood. Importantly we can then also study early risk factors in the children before they develop these conditions. Because our child and adult samples differ in ethnicity and economic situation, we can also study how the development of ICV-MM differs for different groups in society. The student’s studies will further LINC’s efforts in understanding how ICV-MM develops and which circumstances influence this. What we learn will be important for the prevention of ICV-MM in children who are at risk because of their sex, or ethnic or economic reasons. The student will disseminate their research to Welsh government, patient and public involvement groups and charities to develop specific health advice in order to reduce ICV-MM in at risk groups in the future.

We will prepare a complete history of pregnancies for ALSPAC G1 female participants and those of G1 male partners.

This will help us to identify participants who have never enrolled in G2 and ensure we have the correct information for those who have enrolled. We plan to provide summary data for other researchers and produce a data note explaining the variables we have derived.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common diagnosis. It affects around 3% of the population. ADHD has symptoms of hyperactivity, inattention, or both. Although ADHD is usually seen in childhood, it is now accepted that for many, ADHD persists into adulthood. Adults with ADHD are more likely to also have symptoms of depression and anxiety. Without effective management, this can make life more difficult for someone with ADHD.

Both children and adults with ADHD also often report sleep problems. Getting good quality sleep is crucial to someone's health. Sleep problems are also a key aspect of mental health conditions, including anxiety and depression. In this proposal, we set out how we aim to investigate what role sleep disturbance plays in both ADHD and mental health.

This project will use existing measures collected from consenting ALSPAC participants. In particular, we will use measures of ADHD symptoms, sleep, anxiety, and depression. Through statistical analysis, we will explore whether ADHD influences someone's sleep quality. We will build on this by exploring whether a relationship between ADHD and sleep goes on to impact someone's mental health.

Our findings may have consequences for how we view the importance of sleep for someone with ADHD. Crucially, sleep is a modifiable behaviour. Our results may help promote clinical recommendations that consider sleep as a key component of ADHD management.

This proposal will use the dataset for B4541 only. No new data is required.

Social inequality is the unequal distribution of socio-economic (SES) resources which affects people’s standards of living. Typically, individuals from lower SES backgrounds have a higher risk of poor physical and mental health, and children, have an increased likelihood of developing emotional and behavioural difficulties. Multiple factors such as family stress or genetics can influence this relationship between SES position and mental health difficulties. For example, low family income can contribute to difficulty in affording needs and parental distress, which in turn may lead to harsher parenting or family conflict which affect child development. Some of the exposures associated with low SES position can lead to heritable changes in gene expression without altering the DNA sequence which could then affect mental health outcomes. These changes are known as epigenetics, and DNA methylation (DNAm) is the most common epigenetic mechanism through which social inequality can affect gene expression. Low SES position has been previously associated with more alterations to DNAm profiles compared to higher SES positions. DNA methylation occurring in some gene regions have also been observed to associate with child mental health difficulties. Therefore, in this study we propose to investigate the relationship between SES position and child mental health difficulties, and whether this relationship can be explained by epigenetic changes and family functioning. We will make use of multiple methods, most notably structural equation modelling (SEM) for longitudinal analysis of participant data from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Eczema (atopic dermatitis) is a skin condition which causes dry and sore skin. It affects up to 20% of children worldwide. In some children their eczema symptoms will improve and resolve as they get older, but in others the symptoms can persist throughout childhood and severely impact quality of life. If we could identify the children who are likely to go on to have persistent or severe eczema, they could be offered more intensive or different treatment for their eczema. There have been several studies to define subtypes of eczema, such as early-onset resolving or persistent, and to try to identify which early life factors are associated with each subtype. However, the evidence so far is conflicting, there are no clinical risk prediction tools available, and most studies have only involved children of European ancestry. There is a critical need for a clinical risk prediction algorithm that could facilitate teat decision-making in clinic and inform whether emergent treatments are disease-modifying.

This study will analyse existing data from birth cohort studies which include children from a range of ethnic groups. Within each cohort we will group children with eczema into subgroups, according to the age at first symptoms, whether the symptoms come and go over time or are persistent, and the severity of the symptoms. Then we will investigate whether persistent or severe eczema (compared to resolving eczema) is linked to early factors such as family history of eczema, sex at birth, birth weight, ethnicity, breastfeeding and genetic factors.
We will develop prognostic models to help counsel parents on treatment decisions and stratify patients in future clinical trials. Within each cohort, we will also examine a longer list of early life factors that may be more challenging to measure to examine how much they increase the utility of the prognostic models. Comparison of the findings between cohorts will identify common predictors of persistent eczema which could help target treatment to children at risk, and identify areas that may require additional focus.

Emma will be re-using the existing dataset from B3565, no additional data will be required for her student project.
Emma will study rare and common genetic influences on cognitive and behavioural phenotypes in particular, as measured by the Strengths and Difficulties questionnaire across childhood and adolescence. She will analyse exome sequencing and genotyping array data from ALSPAC as well as the Millennium Cohort Study. Her project aims to understand the contribution of genetic effects on cognitive development.

We wish to sequence the genes of ~7,000
ALSPAC children and parents for ~2,000 of them. We will use these data to
identify rare genetic variants, combine these with existing data on common genetic
variants, and then investigate the effects of these variants on the cognitive and
behavioural development of ALSPAC children.
The rationale for this project comes from previous work which has shown that rare
genetic variants in some genes affect children's risk of severe neurodevelopmental
disorders (e.g. intellectual disability, autism), but these variants are often inherited
from parents who appear to have normal cognitive functioning. We have shown
that, on average, these variants affect the normal spectrum of cognition in adults,
as well as mental health traits and reproductive success. We suspect that the effect
of these rare genetic variants might be modified by other more common variants in
individuals’ genomes, which have also been shown to affect cognitive ability, as
well as environmental factors. Furthermore, these effects may change across a
person’s lifetime, and may be modified by the parents’ behaviour and genes.
We wish to use the rich longitudinal data on cognitive development, behaviour and
educational achievement of ALSPAC children at different ages to investigate the
joint impact of rare and common genetic variants on cognitive development, and
whether these are modified by the parents’ behaviour. We will also look at genetic
effects on mental health, as well as behavioural and personality traits relevant to
reproductive success.

The Global Lipids Genetics Consortium (GLGC) is a world-wide collaboration of investigators dedicated to understanding how the different variants in genes can influence the blood levels of lipid traits, such as cholesterol, triglycerides, etc. In our study, we will analyse the association of gene variants with blood lipid levels, considering the effect of age and body-mass index in ALSPAC participants. The results will be combined with results from other groups of participants around the world to be able to identify new gene variants that help understand the biology of blood lipid traits.

A healthy, balanced diet is important for keeping metabolic health and supporting immune system. Obesity is associated with a wide range of metabolic syndromes, including dyslipidemia, hyperglycemia and fatty liver. Hyperglycemia and lipid accumulation may provoke lipid oxidation and further lead to an overproduction of cytokines, hyperactivation of complement system and activation of coagulation system, which all serve as immunological triggers to severe infection of COVID-19 as well as other infectious diseases. With the soaring prevalence of cardiometabolic diseases attributed to obesity and metabolic syndrome, the significance of dietary factors in this context is becoming increasingly emphasized. Mirroring the obesity pandemic in adults, paediatric obesity is also rapidly growing worldwide. As a consequence, metabolic dysfunction-associated steatolic liver disease (MASLD) has become the most common liver disease affecting children1. A concern about paediatric liver diseases is that the disease is likely to persistent into adulthood, conferring a substantial cumulative risk of progressing into chronic liver disease, as well as cardiometabolic dysfunction2. Beyond examining individual dietary components, such as fruits or red meat individually, the impact of overall dietary patterns during childhood on indicators of overall health outcomes, such as blood glucose levels, blood pressure, liver fat and chronic inflammation, in adolescence and early adulthood remain inadequately understood. Moreover, the advent of advanced omics technologies, such as metabolomics, provides a promising approach to elucidate the intricate mechanisms/pathways linking dietary patterns to health outcomes. In the current proposed project, we will explore all the potential associations between dietary patterns and immune response, as well as potential metabolic-related mediators to explain the observed associations between diet and immune response through mediation analysis in the ALSPAC study.