Proposal summaries
B4087 - UK LLC Examining the serological response to SARS-CoV-2 infection and vaccination across the National Core Studies - 03/06/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4088 - Inconsistencies in accounting for age in studies on epigenetic accelerated aging and recommendations for best practices - 01/06/2022
Individuals age at different rates depending a variety of factors such as their genetics, lifestyle and exposure history. Numerous studies have shown that DNA methylation measured in blood and saliva can provide aging estimates that are informative about future risk of death and disease. Through a review of this literature, we uncovered popular approaches that incorrectly evaluate correlations between DNA methylation aging estimates and aging-related disease and their risk factors. We would like to use ALSPAC data to determine the likely implications these incorrect evaluations have had on published findings. In particular, we propose to calculate correlations between aging estimates and disease risk factors in ALSPAC both correctly and incorrectly to determine how much they differ.
B4085 - The structure of HCL-32 in ALSPAC - 01/06/2022
Non-clinical individuals with subsyndromal hypomanic experiences have been shown to be at a heightened risk for developing BD and have been linked to similar severity and impairment experienced by people with BD. A better understanding of the characterisation of hypomania in young people may help improve accurate and timely diagnosis of BD. Despite its potential importance, limited research is available concerning the structure of hypomania among non-clinical young people, particularly in the UK. Therefore, the current study will explore the structure and characterisation of hypomania in a British nonclinical cohort. We propose to examine the distribution and underlying structure of components of hypomania in ALSPAC, along with measure of different psychological and psychopathological dimensions and investigate hypomania symptoms’ association with other psychopathological variables (e.g., substance abuse). Using confirmatory factor analysis and latent class analysis, this study may help explore the structure and characterisation of hypomania in young people. Better understanding of hypomania could provide opportunities for targeted intervention and prevention.
B4076 - The effects of childhood and adolescent physical activity for mental health across future life stages - 30/05/2022
It is well established that physical activity has positive associations with mental wellbeing, and can protect against ill-being and mental health disorders. Further evidence suggests that in general, the most active young people continue to be the most active during adulthood. This infers that more active young people might be at less risk of poor mental health across future life stages. Findings from our recent systematic review (in press) suggested that there was reasonably consistent evidence for a beneficial effect of activities performed between the ages of 5-17 for depression at least 12 months later. Findings relating to anxiety and wellbeing were equivocal and require further research. The current study aims to take an evidence-based approach using the conclusions of our systematic review to direct research methodology. Findings will have implications for public health policy by expanding our understanding of active living in youth and the potiential impact this has on self-reported mental health across future life stages.
B4077 - Using metabolomic data statistics and machine learning to predict severe COVID-19 and long COVID - 30/05/2022
The central idea of the proposed research is to use metabolic biomarkers to predict the severity of COVID-19 and the likelihood of long COVID for individuals that have not necessarily been diagnosed with a pre-existing health condition. To this end, we will use pre-pandemic data from several cohort studies which, in addition to basic information on age, sex, ethnicity, etc, contain hundreds of metabolic biomarkers for thousands of individuals. To understand the link between these characteristics and the impact of COVID-19, we will use symptoms data for those individuals in the cohort studies that had COVID-19. The data will be analysed with statistical methods to identify associations between the characteristics of individuals before the pandemic and the severity of the disease. This analysis will be complemented with computer programs developed to predict if the infection of an individual will have serious effects based on his/her characteristics before the pandemic. Machine learning techniques will be used to train computer programs to automatically recognise metabolic features that represent a risk for severe COVID-19.
B4080 - Does LCT predict milk consumption - 30/05/2022
A single genetic variant (rs4988235) found in the intron of a the gene MCM6 and located -13,910 base pairs from the gene LCT controls the expression of LCT and the production of lactase, an enzyme required to digest lactose sugar commonly found in fresh milk products. In the ancestral state once infants are weened from breast milk the expression of LCT stops, but in some global human populations, including Europeans, the expression of LCT persists into adulthood and throughout one's life leading to what is commonly referred to as lactase persistence. Here we wish to ask if the genetic variant rs4988235 perviously associated with lactase persistence influences milk consumption in ALSPAC mothers.
B4075 - Anxiety and depression in young people who do they affect who seeks treatment and who responds to treatment - 30/05/2022
Anxiety and depression are common mental health conditions, and represent a major cause of distress and disability in young people. We do not yet understand a) which factors predict vulnerability in young people, b) what predicts who seeks treatment, or c) what characterises young people who respond to treatments compared to those who do not. We need to understand risk factors to allow us to target preventative efforts more effectively. Furthermore, understanding what determines who seeks treatment might allow greater outreach and support to be given to underserved populations, and understanding the factors determining treatment response may allow future research into novel treatments to be targeted, and greater clinical monitoring of those at risk of non-response. Performing this research in young people specifically is important: not only are young people at a critical point in life where they are forming relationships and making decisions about education and careers, but successful treatment access and response might also determine their future mental health. We propose to analyse data from the ALSPAC study, among others, to understand the factors affecting all these parts of young people’s mental health pathways. We also aim to produce an online, interactive, browser-based application that a) researchers, educators, clinicians and policy-makers can use to understand who to target prevention efforts towards, and b) so that young people and their families can have access to the same knowledge as those involved in treating them.
B4083 - Social connection as an active ingredient to prevent depression and anxiety in youth - 30/05/2022
The different types of social connections that young people have when they grow up can affect their mental health. Yet we know very little about how these social factors interact with each other and how they impact the development of depression and anxiety in children and young people. We set out to study how, when and for whom social connections work as an active ingredient for the prevention of common mental health problems (depression and anxiety) in children and young people. We use data collected from ALSPAC to investigate how the development of depression and anxiety was impacted by different types of social connections at different stages of their life. We will use data collected about different types of social relationships experienced by the children and young people at different points in time (such as connections with their family, community, online, teachers and friends) to investigate how these affect development of depression and anxiety over time. We will also analyse data collected from respondents when they were children to see if there is evidence to suggest that social connections in early life affect the development of depression and anxiety at later time points.
B4084 - AvonCAP Hospital Study - 11/07/2022
AvonCAP is an ongoing surveillance study, which aims to record detailed information on every adult patient admitted to Bristol’s two large NHS Trusts with symptoms, signs and/or X-ray evidence of acute disease in the lungs. This includes patients with pneumonia, non-pneumonic respiratory infection, exacerbation of chronic respiratory disease (eg asthma, COPD, pulmonary fibrosis) and heart failure. Additionally, we include patients hospitalised with a positive SARS-CoV-2 test. The study is designed to provide comprehensive surveillance of all adults hospitalised with acute respiratory disease in a defined geographic area, thereby providing an accurate estimate of disease incidence. AvonCAP further aims to investigate how lung diseases may be changing during the COVID-19 pandemic, particularly those which may be preventable in the future by new vaccines. This will enable better implementation and design of public health measures, and may be used to determine national vaccination implementation policy.
Health related data is collected for study eligible adults hospitalised at NBT or UHBW NHS Trust, either via consent or under COPI regulations (the study holds CAG approval to use non-consented data). Some study patients also give their consent to provide samples e.g. saliva, nasopharyngeal swabs, etc.
This proposal will identify patients who are in both the AvonCAP and ALSPAC datasets, and allow sharing of specified data fields between the two studies for these patients. Due to the age range of AvonCAP participants, this is likely to include the parents of the Children of The 90s.
Only relevant ALSPAC data fields will be shared with the AvonCAP study team, and will include potential risk factors for lung disease (e.g. occupation and environment factors, pets), details of GP visits and COVID-19 test results. The AvonCAP study will in turn provide data fields of interest to the ALSPAC project.
This proposal allows data collected on participants in these two studies to have added value and greater contribution to the scientific aims of each project.
B4082 - Sex stratified acne GWAS meta-analysis - 27/05/2022
Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Family and twin studies indicate a substantial genetic contribution to acne susceptibility with heritability estimates of 78 and 81%. Genome-wide association studies (GWAS) have made a substantial contribution to the understanding of the genetic basis of several common cutaneous inflammatory disorders. Here we perform a genomewide association analysis, comparing severe cases of acne with controls in females and males separately to identify and replicate genetic determinants.
B4067 - Adverse Childhood Experiences and the onset of mental health symptom stages - 27/05/2022
Adverse childhood experiences (ACEs), such as abuse, threaten individuals’ life-long
well-being. A growing body of research has supported ACEs’ negative influence on long-term
mental health; however, many existing studies measured ACEs by retrospective self-report, that
is, by adults recalling their childhood experiences. However, there is a need to study
prospectively followed cohorts in order to minimise biases in participant selection and
measurement of ACEs. Examining the impact of ACEs on symptom outcomes conceptualised as
stages could help improve our understanding of the staging model in psychiatry. Therefore, this project proposes to explore the prospective impact of ACEs on the progressive stages of mental disorders in adulthood,
B4078 - Genome-wide association study GWAS of lipid traits in adults - 26/05/2022
The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium invites ALSPAC and Bristol researchers’ to take part in a large GWAS of lipid traits (incl. high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides). The main aims of CHARGE’s GWAS are to (1) identify novel loci for lipids trait separately by sex; (2) identify gene-sleep duration interaction effects on lipid traits separately by sex. These analyses will follow the ‘Phase II Analysis Plan for Sleep and Lipids’ version 7.4 provided by CHARGE. Only GWAS summary statistics will be shared with CHARGE. Based on the GWAS results, subsequent analyses (e.g. validation of the gene-by-environment effects using longitudinal data of lipid traits, and Mendelian randomization) would be suggested by CHARGE.
B4074 - Optimising outcomes in children of depressed parents identification of modifiable promoters of mental health resilience - 26/05/2022
Parental depression is associated with various mental health conditions and other difficulties in offspring. Nevertheless, some individuals do not develop mental health difficulties or do so only temporarily. It indicates that certain protective factors may buffer risks associated with being raised by a depressed parent. Individual, family, social, and lifestyle protective factors were identified in previous research to be relevant for mental health resilience in adolescence. However, as people mature, different protective factors may be relevant in young adulthood - a peak period for the emergence of mental health problems.
Therefore, this study will aim to understand if various protective factors could explain why some individuals do not develop mental health problems or recover from them despite being at higher risk due to genetic and environmental influences. Furthermore, we will aim to test the causal role of the identified protective factors and potential biological, psychosocial and environmental mechanisms that could explain protective factors’ joint contribution to mental health resilience in children of depressed parents.
We expect to identify modifiable protective factors that could be targeted to develop prevention and intervention strategies that could potentially interrupt the transmission of mental health problems from parents to offspring. In this way, the research could improve the lives of both depressed parents and their offspring.
B4073 - Mental health trajectories following mental health treatments - 24/05/2022
Mental health treatments, including antidepressant treatment such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Cognitive Behavioural Therapy (CBT) are effective interventions for depression and anxiety in young people. However, the short and long term effects of one or both of these forms of treatment are unknown in longitudinal population studies. There remains a paucity in how these treatments work, what combination of treatments work, what works best for whom, whether some symptoms are treated better than others and how variable mental health responses are following treatment. We will use data recently collected in ALSPAC on mental health treatments and examine mental health responses to address those research gaps. We will develop a longitudinal research tool which highlights these results which will be made freely available to researchers to apply to other research questions.
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.
B4040 - CADSET proposal Obstructive lung function phenotypes and early life - 20/05/2022
It is crucial to understand which early-life factors influence lung function development, since impaired lung function has been associated with respiratory, cardiovascular and metabolic anomalies, and even all-cause mortality. This project will focus on further understanding how lung function develops and what early life factors are key at imparing its development.
B4062 - C-section Delivery and blood DNA Methylation at Birth and in Childhood - 20/05/2022
Emerging evidence suggests that babies born by C-section (Cesarean section) have different hormonal, physical, bacterial, and medical exposures, and that these exposures can subtly alter neonatal physiology. (Sandall et la, 2018) C-section delivery has been associated with a number of chronic disease outcomes in children, including metabolic risk phenotypes and asthma. One of the potential mechanisms through which C-section delivery may increase risk of adverse health outcomes is via epigenetic alterations. (Dahlen et al, 2013)
Dahlen, HG et al. “The EPIIC hypothesis: intrapartum effects on the neonatal epigenome and consequent health outcomes.” Med Hypotheses. 2013. May; 80(5):656-62.
Sandall, J et al. “Short-term and long-term effects of caesarean section on the health of women and children.” Lancet. 2018. Oct 13; 392(10155):1349-1357.
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.