Proposal summaries
B4064 - Associations of diabetic traits blood pressure general and central adiposity with COVID-19 and long COVID a prospective study - 20/05/2022
COVID-19 patients with high BMI and waist to hip ratio (WHR), diabetes and hypertension showed a higher risk of dying and severe disease in the early pandemic (1-3), but the role in susceptibility for COVID-19 and long COVID and the extent to which associations are due to confounding is still mostly unclear (4-7). Previous analysis on infection and long Covid risk mainly used binary measures of obesity or overweight, known diabetes status and hypertension, which could introduce measurement error, reduce statistical power, and does not allow to disentangle whether an association is related to treatment or due to the disease itself. Using pre-pandemic diabetes, measured blood glucose and HbA1c, BMI, WHR, body fat and blood pressure could improve measurement quality by identifying disease control, severity, and those with prediabetes.
B4066 - Exploring the pathways between mental health symptom stages from early adolescence to young adulthood - 20/05/2022
Early adolescence is a sensitive period of significant social and physiological growth, and represents the time when symptoms of mental disorders commonly emerge. Clinical staging models have been proposed to provide framework for identifying early risk factors and symptoms in adolescence and young adulthood, that may predict future progression to mood disorders and psychosis. It has been suggested that sub-threshold symptoms may be predictive of later stages of more serious mental disorders. We propose to examine the associations between parent rated sub-threshold mental health symptoms in early adolescence and mental health symptom stages in young adulthood. This will help determine which of these symptoms could represent risk of progression to stages associated with need for care. Parents offer unique insight into early mental health symptoms, observing their children in a home environment. It is important to understand the trajectories associated with parental accounts. If specific parent rated sub-threshold symptoms in early adolescence can be identified, that are predictive of progression to later stages of mood, anxiety and psychotic symptom stages in young adulthood, this could provide understanding of prognosis and intervention needs to adolescents and their families. Cannabis use, alcohol use and negative life events may mediate the relationship between parent rated symptoms in early adolescence and mental health difficulties in young adulthood. We propose to analyse these pathways in order to understand whether these factors are associated with increased risk of progression to later clinical stages. This project will contribute to understanding the validity of clinical staging models for psychotic and mood disorders in youth mental health, in particular contributing to understanding of early risk factors in these models, and could provide opportunities for targeted intervention and prevention.
B4070 - Rapid evaluation of interventions for close contact infectious diseases - 31/05/2022
During the COVID-19 pandemic, ALSPAC ran a rapid survey of risk mitigation behaviours. We used the data to inform a transmission model of the SARS-CoV-2 Omicron-variant wave. We would like to develop the methods we started during the COVID-19 pandemic to create a public health decision-making tool. We propose to work with the ALSPAC cohort to characterise infection prevention practices and to understand the trade-offs between measures.
B4071 - Childhood adversity DNA methylation risk scores and risk for depression across development - 20/05/2022
Childhood adversity (e.g., abuse or maltreatment, family disruption or dysfunction, poverty, etc.) is one of the most potent life experiences linked to depression, nearly doubling the risk for a first onset. Emerging evidence also suggests that the effects of adversity on depression may vary based on when in the lifespan it occurs. In other words, there may be sensitive periods when the brain is “plastic” and experiences can impart more enduring effects field. However, the biological mechanisms linking childhood adversity to long-term vulnerability for depression remain poorly understood. One possibility is that adversity reprograms the epigenome through DNA methylation (DNAm), epigenetic modifications that do not change the sequence of the genome, but can alter gene expression. Recent evidence also suggests that DNAm risk scores (MRS) generated from large-scale studies of early-life exposures and/or mental outcomes may help predict and interpret risk for depression and other mental disorders.
To this end, we recently completed the largest analysis of time-varying childhood adversity and genome-wide DNAm in childhood, analyzing the impact of five types of adversity across seven longitudinal birth cohorts (N=2,347-3,279). Through these analyses, we identified distinct epigenetic signatures for five types of childhood adversity, as well as further evidence of sensitive periods for the effects of adversity on DNAm. However, it remains unknown whether DNAm risk scores generated from these data can accurately explain and predict depression risk across development.
As such, we seek to extend this research, which included data from the ALSPAC cohort, to further investigate the relationship between childhood adversity, DNAm, and depressive symptom trajectories across development. The central hypothesis we will test is that DNA methylation patterns linked to childhood adversity can be used as predictors of both prior exposures to adversity and future depressive outcomes, with measurable effects on depressive symptom trajectories.
B4069 - Autistic traits anxiety and eating behaviours Longitudinal trajectories across child development - 20/05/2022
Recent empirical work suggests the prevalence of eating disorders may be raised in autistic individuals, however, questions remain as to whether the co-occurrence of autism and eating disorders could be due to selective samples and/or difficulties disentangling symptoms of autism as compared to symptoms of eating disorders. An alternative explanation is that autism, or high levels of autistic traits, in childhood, may causally increases risk for eating disorders later in development. In addition, autistic children often experience high level of anxiety, and might use overeating or binge eaitng as a coping strategy to sooth and calm themselves down, which might put them on increased risk for later eating disorders. Further research into the pathways and potential mediators of the link between autism, anxiety,and eating disorders is needed to illuminate underpinning mechanisms, which in turn will highlight targets for prevention/intervention.
B4072 - Subtypes of persistent developmental stammering - 20/05/2022
There are speech therapies that can help them to cope, but most children will recover on their own. However, about one person in every hundred keeps stammering into adulthood. Stammering is tends to run in families, which means that it is genetic. There are also markers in the brain that help us to understand how stammering happens. However, they don’t seem to be very consistent across people. This project proposes to use a big data base of Magnetic Resonance Imaging (MRI) and genetics data covering thousands of parents and children, many of whom will have stammered. These data will be used to understand both how the brains of people who stammer are different from fluent speakers, and how they are different from each other. With a greater understanding of what makes some brains stammer, it is hoped that we can inform the development of better speech therapies. People who stammer also have a strong interest in understanding why they are the way they are and are growing community advocacy movements around the idea of neurodiversity. These advocacy groups will benefit as we learn just how diverse their brain can be.
B4068 - Understanding the mechanisms linking the urban environment to mental health in childhood adolescence and early adulthood - 25/05/2022
Individuals who are raised in urban (versus rural) settings are around twice as likely to develop a psychotic disorder such as schizophrenia. Research also suggests that risk for other mental health problems, in particular depression, anxiety and conduct problems, is elevated in urban settings. Given that 70% of the world’s population will live in urban areas by 2050, it is essential that we uncover the pathways linking cities and psychosis so that we can inform intervention efforts.
Air and noise pollution are among the biggest environmental health risks that the world faces, and are particularly problematic in cities. Growing evidence also suggests that air pollution may contribute to the development of mental health problems. However, it is currently unknown whether air and noise pollution might partly explain the elevated risk for mental health problems found in cities. In addition, there has been a lack of longitudinal research, including that using pollution spanning the early years of development. Studies have also often been inadequately controlled for potential confounders.
This project will examine 1) the longitudinal associations of air pollution exposure from pregnancy to age 15 with psychotic experiences at age 12, 18, and 24; and examine specificity by repeating analyses with anxiety, depression, and conduct problems as outcomes; 2) explore the interplay between neighbourhood social characteristics (crime and social fragmentation) and air pollution in the emergence of psychotic experiences, and 3) examine two potential biopsychological mechanisms linking urban neighbourhood exposures with mental health, namely inflammation and cognition.
B4065 - The Impact of Early Child Development on Social Mobility in the UK - 13/06/2022
The main research question that this project will address is: how do parental investments and parenting practices in the pre-school years influence the formation of human capital in children and contribute to the transmission of socio-economic status between generations.
During the pre-school years, though there are many outside influences on children, it is parents that have the greatest impact on their offspring. Parental investments before the age of three are likely to be as important, if not more, than what happens from age three onwards, given the dynamic complementarity between early and later skill development.
The project aims to extend our understanding of how (and when) gaps in attainment across socio-economic status emerge. We will map the relationships between measures of parental investment in the early years and long-term socio-economic outcomes and investigate the extent to which these are mediated through educational attainment. The empirical analysis will use data from the Avon Longitudinal Study of Parents and Children (ALSPAC) with linkage to the National Pupil Database. The data will be used to empirically investigate the extent of differences in early child investments and parenting practices between children/parents and how any differences relate to the later life outcomes of the children.
B4063 - Determinants of breastfeeding success and health inequalities - 10/05/2022
Breastfeeding is sustainable, the biological norm, and potentially life-saving, particularly for premature babies. Evidence-based strategies to support breastfeeding have been successful, but inequalities in breastfeeding rates are proving difficult to reduce, affecting the most vulnerable of mothers and babies. Successfully establishing and sustaining breastfeeding can be facilitated by both removing structural and cultural barriers, and overcoming individual challenges. Common factors such as obesity and depression/anxiety could play an important part in explaining some of the variability (and inequality) in breastfeeding duration. Conversely, maternal factors reflecting good mental and physical health could increase resilience to contexts with low systemic and cultural support for breastfeeding, such as the UK. However, the evidence on the individual determinants causally influencing successful and sustained breastfeeding is of poor quality. The identification of causal determinants of early cessation will improve breastfeeding support activities.
B4061 - Prevention of high levels of depression across adolescence and young adulthood the role of active ingredients - 03/05/2022
Depression is the leading cause of disability worldwide and is a major contributor to the overall global burden of disease, with more than 350 million people of all ages suffering from depression. Especially when recurrent and with moderate or severe intensity, depression may become a serious health condition. Further, we now know that many young people suffer from clinical depression. In fact, major depression is one of the most common mental health disorders in children and adolescents, with an estimated one year prevalence of 4-5% in mid-late adolescence and 5.6% in young people of 13-18 year old. Depression in young people is a precursor of adult depressive disorder which is strongly linked to poor physical health outcomes, lower income and increased unemployment, with half of those with lifelong recurrent depression starting to develop their symptoms before the age of 15 years. Thus, to recognize and treat depression in young ages is crucial. To sum up, depression is a substantial and largely unrecognized problem among young people that warrants an increased need and opportunity for identification and intervention. Understanding how specific factors might prevent and/od be effective in the treatment of depression in young people is crucial for the development of early intervention and treatment of depression among youths.
Depression results from a complex interaction of social, psychological, and biological factors. Recent attempts have been made by the Wellcome Trust to investigate the evidence for different active ingredients (i.e. those aspects of an intervention that drive clinical effect, are conceptually well defined, and link to specific hypothesised mechanisms of action) deemed to help prevent, treat, and manage depression in young people globally, including behaviours and activities, beliefs and knowledge, brain/body functions, cognitive and attentional skills, human connections, and socioeconomic factors. However, what is still unknown is which of these potential active ingredients and/or which combination of these active ingredients constitute a more accurate predictor for different groups of young people with depression, including those with high levels of depression.
A number of important issues need further investigation to aid early intervention in depression. First, most studies in young people with depression have focused on single time points, while very few studies have investigated the different trajectories of depression across adolescence and young adulthood, including young people with persistent high levels of depression. In addition, despite the recent attempt to identify specific active ingredients of effective interventions for depression, it is still unclear which of these active ingredients (and their combinations/interactions) are the most relevant to prevent depression across childhood and adolescence. For this reason, new statistical approaches, including predictive modelling are required and will help advance the field of early intervention in depression.
Therefore, the main purpose of this research proposal will be to characterize the most relevant active ingredients (and their combination) that prevent the development of persistent high levels of depression across adolescence and young adulthood. More specifically, we will aim to answer to the following main research questions: "What combination/s of active ingredients prevent the development of persistent high levels of depression across adolescence and young adulthood?"
To do this, we will use the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, which is a longitudinal birth cohort study, set in the UK, examining the determinants of development, health and disease during childhood and beyond.
B4052 - Gaining Insights Into The Causal Effects Of Electronic Cigarette Use - 03/05/2022
E-cigarettes can help people stop smoking, but the long-term effects of e-cigarette / vaping initiation remain unknown. In this project, we will use our newly established Genetics, E-cigarette and Nicotine Consortium (GENiC) to identify genetic variants associated with vaping. This will provide information about the biological determinants of individual differences in vaping and support causal inference analyses into the downstream behavioural and health consequences of vaping.
At present, it is difficult to determine which genetic variants are specifically associated with vaping rather than smoking combustible cigarettes because most e-cigarette users have also smoked. However, data on non-smoking e-cigarette users are now emerging in large, genetically-informed cohort studies like ALSPAC, which enables – for the first time – the identification of genetic variants associated with vaping initiation (i.e., using e-cigarettes regularly or more than 100 times) in smoking-naïve young people.
We plan to use the available genetic data in ALSPAC and data relating to smoking and e-cigarette initiation to investigate whether a person’s genetic information can be used to predict e-cigarette initiation.
B4060 - UK LLC Association of COVID19 and Long COVID with disruption in employment and finances - 06/05/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4058 - The associations between dietary pattern and immune response the mediating roles of metabolic syndrome - 03/05/2022
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. 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 several population-based cohort studies.
B4055 - Physical Activity throughout Adolescence and Cardiac Structure and Function in Early Adulthood - 25/04/2022
This project will examine whether adolescent physical activity is related to heart function in adulthood. This will be investigated by comparing physical activity levels and measurements of heart structure and function as collected in the Avon Longitudinal Cohort Study of Parents and Children.
B4057 - Epigenetic signatures Association with hormone levels and age - 07/06/2022
Adrenarche is a developmental stage, occurring around ages 6-8 years, during which the adrenal glands produce increasing levels of the steroid hormone DHEAS. The function of this hormone, although extremely abundant in human circulation, is still unclear. Elevated levels of this hormone during this prepubertal stage are associated with earlier pubertal events and susceptibility to developing polycystic ovarian syndrome. Thus, we suspect this hormone has a substantial effect on various physiological systems, including the reproductive axis. Due to its chemical similarity to other steroid hormones, such as estradiol, we suspect it conveys its effect through the induction of epigenetic modifications, such as DNA methylation. Here, we would like to identify epigenetic modifications that are associated with DHEAS levels, using available data from girls at this developmental transition.
B4056 - How does university attendance impact on mental health trajectories of young people - 03/05/2022
The mental health of university students is a growing public health concern (1). Findings from population-based studies in the USA, UK and Norway point to a significant increase in mental distress among students over the last decade (2-5). Around 5% of young people in the UK have a diagnosis of either anxiety or depression, and the rate of people attending university has doubled in the past twenty years (6). For many the transition to university coincides with a developmentally high-risk period for the emergence of mental health concerns (7-9). This risk may be made worse by the need to adjust to a new social and academic environment whilst at the same time becoming financially independent (8, 10). This period could be particularly risky for students who have faced adversity, are socially disadvantaged (11), or for people who find it harder adjust to new social groups (8, 9). Few long-term studies have looked at these issues (12). While some evidence has shown how many students are likely to experience a mental disorder and use a mental health service at university (13); we do not currently know how much mental health need occurs prior to university attendance. By understanding this and any risk factors for the emergence and development of mental health need at this transition we could inform support-based prevention for students. This study aims to use data collected in ALSPAC to understand the risk university attendance poses on mental health and service use for a mental health reason among young people.
1. Barkham M, Broglia E, Dufour G, Fudge M, Knowles L, Percy A, et al. Towards an evidence-base for student wellbeing and mental health: Definitions, developmental transitions and data sets. Counselling and Psychotherapy Research. 2019;19(4):351-7.
2. Knapstad M, Sivertsen B, Knudsen AK, Smith ORF, Aarø LE, Lønning KJ, et al. Trends in self-reported psychological distress among college and university students from 2010 to 2018. Psychological Medicine. 2021;51(3):470-8.
3. Lipson SK, Lattie EG, Eisenberg D. Increased Rates of Mental Health Service Utilization by U.S. College Students: 10-Year Population-Level Trends (2007-2017). Psychiatric services (Washington, DC). 2019;70(1):60-3.
4. McManus S, Gunnell D. Trends in mental health, non‐suicidal self‐harm and suicide attempts in 16–24-year old students and non-students in England, 2000–2014. Social Psychiatry and Psychiatric Epidemiology. 2020;55(1):125-8.
5. Tabor E, Patalay P, Bann D. Mental health in higher education students and non-students: evidence from a nationally representative panel study. Social Psychiatry and Psychiatric Epidemiology. 2021;56(5):879-82.
6. Boero G, Nathwani, T., Naylor, R., Smith, J. Graduate Earnings Premia in the UK: Decline or Fall. Higher Education Statistics Agency (HESA): HESA; 2021.
7. Kessler RC, Amminger GP, Aguilar-Gaxiola S, Alonso J, Lee S, Ustün TB. Age of onset of mental disorders: a review of recent literature. Curr Opin Psychiatry. 2007;20(4):359-64.
8. Lei J, Brosnan M, Ashwin C, Russell A. Evaluating the Role of Autistic Traits, Social Anxiety, and Social Network Changes During Transition to First Year of University in Typically Developing Students and Students on the Autism Spectrum. Journal of Autism and Developmental Disorders. 2020;50(8):2832-51.
9. Adams KL, Saunders KE, Keown-Stoneman CDG, Duffy AC. Mental health trajectories in undergraduate students over the first year of university: a longitudinal cohort study. BMJ Open. 2021;11(12):e047393.
10. McCloud T, Bann D. Financial stress and mental health among higher education students in the UK up to 2018: rapid review of evidence. Journal of Epidemiology and Community Health. 2019;73(10):977-84.
11. Cullinan J, Walsh S, Flannery D. Socioeconomic Disparities in Unmet Need for Student Mental Health Services in Higher Education. Applied Health Economics and Health Policy. 2020;18(2):223-35.
12. Lewis GM, T. Callender, C. Higher Education and Mental Health: Analyses of the LSYPE cohorts: research reports. In: Education. Do, editor. 2021.
13. Eisenberg D, Hunt J, Speer N. Help seeking for mental health on college campuses: review of evidence and next steps for research and practice. Harvard review of psychiatry. 2012;20(4):222-32.
B4038 - Psychosocial and Biological influences on sexual orientation disparities in mental health outcomes - 10/05/2022
Non-heterosexual (bisexual, lesbian, gay, and asexual) adolescents are at greater risk of common mental health disorders compared to heterosexual adolescents. The dominant theoretical framework used to explain the elevated rates of mental disorders among non-heterosexuals is minority stress theory. However, this model cannot fully explain sexual orientation disparities in mental health outcomes. Thus, other mechanisms or explanations, may help explain the sexual orientation disparities in mental health outcomes should be further explored. In addition, many adult mental health problems begin in childhood or adolescence. Non-heterosexual adolescents may be at greater risk of poorer mental health even in early childhood compared with heterosexual adolescents, which cannot be explained by the minority stress theory since when sexual identity development is nascent. However, the underlying mechanisms remained under-explored. Thus, this project aims to further test the psychosocial and biological influences on the sexual orientation disparities in mental health outcomes, especially in childhood, early adolescence, and the developmental trajectories from childhood to adolescence.
B4034 - Using genetics to understand causal mechanisms underlying pregnancy outcomes for mothers and babies - 21/04/2022
**Please note that this project is linked to our existing B3392 project and will mostly require variables that we already have in Exeter in the B3392 dataset.**
References to previously published work in the summary below are given as PubMed IDs.
Maternal smoking during pregnancy is associated with various adverse pregnancy outcomes. Despite a strong public health message, many pregnant women continue to smoke. Studies and data analysis indicate that maternal smoking is associated with a reduction in offspring birth weight (PMID: 33173933 and PMID: 22956269), which is likely to be due to an adverse effect of smoking on placental function. Placental weight is often used as a convenient indicator of placental function (PMID: 32421535). However, information on the effect of smoking during pregnancy on placental weight is limited. The literature reports both lower and higher placental weights for women who smoked during pregnancy, relative to those who did not smoke (PMID: 32421535 and PMID: 29947760). We aim to gain a better understanding of the risk of smoking during pregnancy by using genetics to test whether smoking is causally related to placental weight, and to better understand the underlying mechanisms connecting smoking, placental weight and birth weight. So far, the team in Exeter have used ALSPAC and other studies to identify genetic variations in both mothers and babies that are associated with birth weight (PMID: 31043758), to show that genetic variation influences how likely women are to quit smoking in pregnancy (PMID: 19429911), and to show that this same genetic variation influences birth weight via its effect on smoking (PMID: 22956269). The current project will build on those findings and relate smoking, birth weight and placental weight.
B4049 - Cardiovascular risk factor trajectories and subclinical phenotypes in young people with and without type 1 diabetes - 21/04/2022
Cardiovascular disease (CVD) is the primary cause of premature morbidity and mortality in type 1 diabetes, with this effect particularly pronounced in those diagnosed at a younger age. The magnitude of this problem has recently been starkly highlighted by findings from the Swedish National Diabetes Register, where patients diagnosed with diabetes between 1 and 10 years of age were found to have a 10× higher risk of future acute myocardial infarction compared to those diagnosed between the ages of 26 and 30 years, and over a 30× higher risk than the general population. These and other data suggest that adolescence may be a particularly crucial time in the development of future CVD complications in type 1 diabetes, and that effective intervention at this age may offer long-lasting benefits for cardiovascular health.
While compromised glycaemic control represents the major risk factor for CVD complications in type 1 diabetes, individuals living with the disease are also exposed to many other well-established and potentially modifiable risk factors faced by the population at-large. Obesity is a well-established causal driver of subclinical disease in the young, is known to track into adulthood, and therefore represents one of the major risk factors in early-life for future risk of CVD. Although individuals with type 1 diabetes have traditionally been considered to be a relatively lean population, recent evidence has shown that obesity rates in this group are now similar or possibly even higher than in the general population, with an alarmingly high prevalence in children and adolescents.
For the last 14 years, our group have tracked, genotyped, and extensively phenotyped a cohort of adolescents with type 1 diabetes; first as part of a randomised clinical trial (The Adolescent type 1 Diabetes cardio-renal Intervention Trial - AdDIT), and then as part of a long-term epidemiological study (AdDIT Follow-Up). We now wish to use this data alongside that collected over the same timespan in ALSPAC to address the following aims and objectives:
B4046 - Investigating the association between birthweight and intellectual disability - 22/04/2022
Cognitive delay has previously been found to be associated with low birthweight. Little research has been conducted to explore the specific association between low birthweight and intellectual disability (defined as having an arrested or incomplete development of the mind alongside functional impairment in facets that contribute to overall intelligence such as cognition, language and social ability), particularly among populations that were born at an appropriate gestational age. The current project will explore the observational association in ALSPAC before going on to investigate potential moderating factors (factors that influence the strength of the effect). We will then investigate whether the association is likely to reflect a causal effect by using techniques such as Mendelian Randomization.