Subtle differences in a person's genes can affect their susceptibility to disease and cause them to respond differently an environmental exposure compared to other people. Interestingly, some people may develop a disease after being exposed to specific genetic and enviromental factors while others may not.

This project will combine genetic and environmental information from thousands of people aiming to understand how these factors influence risk to disease and characteristics like immune system response and vision.

As we learn more about the connection between genes and the environment, we can pursue new approaches for preventing and treating disease.

Across the developed world, employment has declined in middle-wage "routine" jobs and increased strongly in jobs requiring a degree. Recent evidence from the U.S. and Sweden indicates this change is associated with an increase in the demand for jobs requiring social skills. Over the last 30 years the UK labour market has witnessed a well-documented increase in the supply of graduates while the occupational structure has shifted towards managerial jobs. However, there is no strong evidence as yet that these changes have benefitted workers with higher social abilities.

In this project we will investigate the labour market returns to social skills in the context of the UK. Thanks to the availability of long-running cohort studies, the UK offers an opportunity to examine unique data on individual’s characteristics, such as cognitive, socio-emotional, and physical abilities. ALSPAC is particularly suitable to our purposes as it collects detailed information on these abilities.

The changing labour market is at the centre of some of the most important social policy debates worldwide, especially those focused on the effect of artificial intelligence on the demand for different types of skills. We will contribute to these debates by providing novel evidence of the relationship between different types of skills and labour market outcomes.

Alcohol use disorders (AUDs) affect over 100 million people worldwide with alcohol use accounting for 4.2% of global disability adjusted life years (DALYs) (Degenhardt et al. 2018).
Adolescence and young adulthood is recognised as a critical window for the development of AUDs due to the vulnerability of the corticolimbic system to alcohol-induced damage during this period (Nixon and McClain, 2010). AUDs commonly develop during late adolescence and early adulthood, with a median age of onset for alcohol abuse of 21 and alcohol dependence of 23 (Kessler et al, 2005). Adolescent alcohol use has both immediate and longer-term effects on the development of AUDs. In adolescents that used alcohol for the first time between the ages of 11 and 14 the rate of alcohol dependence measured ten years post exposure was 15.9% in contrast to those who used alcohol for the first time after the age of 19, where rates of alcohol dependence ten years post exposure were only 1% (DeWit et al, 2000). A prospective cohort study in the UK demonstrated that following adjustment for other predictors, frequent teenage alcohol use and antisocial behaviour held persisting and independent associations with later alcohol dependence (Bonomo et al 2004).
Early life stress and traumatic experiences are widely recognised to contribute to AUDs in humans (Viner and Taylor, 2007). In the UK the association between trauma and substance use disorders has been recognised by the Department of Health with services required to use a trauma-informed model of addiction care (Clinical Guidelines on Drug Misuse and Dependence Update 2017). In epidemiological studies the presence of Adverse Childhood Events (ACEs) is associated with an earlier onset of alcohol use and increased levels of alcohol consumption (Rothman et al. 2008). ACEs specifically linked to alcohol use include physical abuse, sexual abuse, having a mentally ill household member, substance abuse in the home, and parental discord or divorce (Rothman et al. 2008). All forms of childhood trauma act as risk factors for adolescent binge drinking; with earlier adverse alcohol consumption potentially lying on the causal pathway between trauma and alcohol use disorders (Shin et al. 2009). One pathway that may explain how early life adversity and adolescent alcohol use lead to AUD in adulthood is through long term changes in gene expression as a result of epigenetic modification. Exposure to early life adversity and adolescent alcohol use independently lead to long-term epigenetic changes (Houtepen et al. 2016, Kyzar et al. 2016). Markers of early life adversity have been demonstrated to show conserved epigenetic changes between human and rat hippocampal tissue providing scope for translation between preclinical and epidemiological studies (Suderman et al. 2012).
This study aims to explore the interaction between early life adversity and adolescent alcohol use in the development of alcohol use disorders in adulthood using the ALSPAC cohort. This study will quantify ACEs in the ALSPAC cohort using previously developed approaches (Houtepen et al. 2018) and develop an approach to quantify adolescent alcohol use. These measures will be used as predictors of a diagnosis of AUD using DSM V criteria at age 25. Epigenetic associations with early life adversity and adolescent alcohol use will be explored with the intention of using these findings to bridge between this study and a parallel programme of preclinical experiments taking place Department of Physiology, Pharmacology and Neuroscience at the University of Bristol.

A wealth of data implicates inflammation in the pathophysiology of psychiatric and many other disorders. Childhood adversity is a risk factor for later psychiatric disorder and it is associated chronic inflammation as measured by the soluble urokinase-type plasminogen activator receptor [suPAR]). We have shown that suPAR is elevated among ALSPAC participants who have psychotic experiences and psychotic disorder at age 24. We have also shown that the complement pathway in the blood, which contributes to inflammation, is upregulated in the blood 6 years prior to the identification of psychotic disorder (PMID 29036721). Similarly we have shown that people at clinical high risk for psychosis who later develop a psychotic disorder show increased baseline levels of markers of the complement pathway (PMID 32857162). Most recently we have shown (preliminary data) that the complement pathway is upregulated among those in the first episode of psychosis who respond well to antipsychotic drugs. These findings implicate the complement pathway in psychosis. Of the members of the complement pathway that have been shown to be dysregulated, C1r, has been most consistently and strongly altered and has been validated using ELISA (PMID 32857162; PMID 32857162). C1r is linked to the activation of C4A variant implicated so strongly in schizophrenia genomic studies (PMID: 26814963) and is associated with other medical diseases such SLE and Hereditary Angioedema.
What is not known is:

1. what is the relationship of this marker of chronic inflammation [suPAR] and this plasma marker of the complement pathway, C1r, at age 24 to adversity in childhood and adolescence

2. what is the relationship between plasma suPAR and plasma C1r.

3. do measures of suPAR and C1r at age 24 mediate the relationship between adversity in childhood and adolescence and psychiatric outcomes at age 24.

We propose to answer these questions by quantifying these markers of chronic inflammation and complement activation in all young people who gave bloods in the ALSPAC clinics at age 24 to investigate the relationship to adversity and psychiatric outcomes at age 24.

We note that chronic inflammation and complement pathway function is an important contributing factor to many medical diseases and that this information can therefore be applied broadly and will find relevance far beyond the field of psychiatry.

This work aims to improving our understanding of the emergence of mental health problems across childhood, adolescence and young adulthood. We will investigate how different biological and environmental factors interact to drive or prevent the onset of mental ill-health.

Respiratory disease, the third largest cause of death in England, affects one in five people. Hospital admissions for lung diseases drive NHS winter pressures, costing £11billion annually. Reducing the impact of respiratory disease and associated health inequalities is a UK Government priority (UK Life Sciences Vision 2021).
In collaboration with ALSPAC we will focus on
• Workstream 2: Asthma and chronic obstructive pulmonary disease (COPD)

Using advanced imaging and novel mathematical approaches, we will identify spatio-temporal brain networks that show altered dynamics in young adults with genetic risk for Alzheimer's disease. The PhD will provide grounding in network neuroscience — an evolving field using network theories to study the brain across multiple scales and modalities.

Dental caries a complex chronic disease of multifactorial etiology that affects a children worldwide. Its risk factors include a susceptible tooth, fermentable sugars and caries bacteria. Certain upstream factors have also been implicated in the etiology of dental caries and they are those that promote a favorable oral environment for dental caries susceptibility and progression. One of such upstream factors is prenatal smoking. The prenatal period is a sensitive time for fetal growth and development, including the development of the primary tooth germ that commences at the end of the 5th week of gestation. Exposure to prenatal smoking during this critical period not only affects the health and wellbeing of the developing fetus but also the quality of the developing tooth. Previous studies that have found an association between prenatal smoking and dental caries in the child relied on self-reported smoking during pregnancy, and thus, susceptible misreporting and recall bias of actual smoking status. This current study utilizes an objective measure of exposure to smoking in-utero in the form of newborn DNA methylation (DNAm) measured in cord blood collected at birth.

Disordered sleep is commonly reported in autism from a young age, as are symptoms of mental illness. Mental health and sleep are known to influence each other in a bidirectional manner within the general population, but the nature of the association between sleep and mental health problems in autism is poorly understood. Moreover, the underlying causes of sleep problems in autism are unknown. Thus, current treatments for sleep problems are largely ineffective in autistic people, and they also face severe consequences of mental ill health, such as high rates of suicidality and in-patient care. We aim to characterise the relationship between sleep problems and mental ill health, and identify factors underpinning the sleep problems in autism and in people with autistic traits. We will focus specifically on childhood and adolescence as this comprises the typical age-range of onset for problems in both sleep and mental health. Our approach to answering these questions will involve statistical modelling of longitudinal data on sleep and mental health in ALSPAC.