Proposal summaries
B3503 - The impact of public health measures adopted to control the COVID-19 pandemic on mental health of parents and children risk and - 17/04/2020
The impact of the public health measures adopted to control the COVID-19 pandemic on the mental health of parents and children is unknown but is likely to vary by existing vulnerabilities and social inequalities. New information is vital to inform future policies and recovery. A number of rapid cross sectional surveys have started to collect data on adult and young peopleâs mental health during the COVID-19 crisis. However, such designs lack important information about mental health preceding the pandemic to more accurately understand changes and risk or resilience to showing a rise in emotional and behavioural problems. Thus, data in longitudinal studies is especially important. There are over 800 ALSPAC next generation children ranging in age from 0 â 11 years, with the majority at the younger ages of under 8 years. This is also an age range which has not been included in existing efforts nationally, with existing surveys focusing on school age or above. In ALSPAC-G2 children and their parents have already provided data from their parents before and during pregnancy and in the children from birth. Pre-pandemic measures include mental health in parents (and grandparents) and emotional and behavioural problems in children. By re-contacting families at this time and sending a brief online questionnaire to repeat emotional and behavioural problems scales, as well as COVID-19 specific worries matched to other national surveys, we can understand the immediate impact of this crisis on children, the extent to which this is linked to the impact on parents and possible protective strategies such as keeping routines, as well as track this as the cohort grow up.
B3507 - Alcohol 18 to 30 - 24/04/2020
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 âdeaths of despairâ that have reduced life expectancy â 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 â 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 âsafeâ or ânon-riskyâ levels of drinking â and clear benefits from reducing average consumption. The UK in line with other countries issued new guidelines on safe drinking levels â which are now the same for men and women â 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 â 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 â 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 âsnareâ 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.
B3502 - Adult peak Circulatory capacity Mechanisms and Exposures ACME - 14/04/2020
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.
B3501 - Alcohol use in the late 20s - 14/04/2020
Data collection
B3497 - Investigating the Genetic Architecture and Risk Factors of Epilepsy - 07/04/2020
Epilepsy is a neurological disorder that affects one percent of the population. Genetic factors play a role in epilepsy, but the full spectrum of the genetic architecture for this disorder is unknown. Previous work indicates that rare variation may contribute to epilepsy risk, but large sample sizes are required to increase the likelihood of identifying new risk genes or variants. The goal of this project is to investigate the genetic components of epilepsy in a large, well-characterized epilepsy cohort, in collaboration with Epi25, a consortium of over 50 epilepsy investigators. Whole exome sequencing (WES) data from epilepsy samples generated at the Broad Institute will be analyzed with ALSPAC WES data and other locally available or dbGaP-sourced controls to identify genes or variants associated with epilepsy. The inclusion of the ALSPAC data will be a valuable contribution to increase power in downstream analyses.
B3500 - Examining the association between childhood bilingualism and cognitive functioning in adulthood - 07/04/2020
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 childâs 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.
B3494 - Metabolomic association studies of cortical thickness and microstructural properties of the brain in children and adolescents - 06/04/2020
B3493 - Pervasive vs Situational ADHD Mechanisms Trajectories Comorbidity Gender Differences and Long-Term Outcome - 06/04/2020
ADHD is a condition marked by symptoms of inattention and hyperactivity/impulsivity persistent over time, present and causing impairment in at least two contexts, such as in the school and at home. However, the degree to which symptoms are present across situations varies from individual to individual. At one end of the spectrum, children may show severe symptoms in several contexts (that is, pervasive ADHD) while others show severe symptoms only in one context (that is, situational ADHD). What underpins the pervasive and situational manifestations is not well understood, and the impact of pervasive and situational dysfunction on future outcome (such as mental health, occupation, and educational status) needs further investigation. Different underlying mechanisms may relate in specific ways to the degree to which ADHD is expressed pervasively or situationally in the school or home setting. In the current study, we focus specifically on the role of executive functioning (that is, goal-directed behavior), emotion processing, and aspects of the family environment, in this matter. We will examine how pervasive and situational ADHD symptoms evolve over time, mapping possible underlying mechanisms, gender differences, and long-term outcome in a large community sample. The findings will have implications for our understanding of the etiology, maintenance, treatment, and prevention of the diagnosis.
B3496 - Understanding the intergenerational transmission of risk for offspring mental health cognitive and educational outcomes - 20/04/2020
Parental risk factors are among the strongest early predictors of offspring mental health, cognitive and educational outcomes. This transmission of risk across generations hinders social mobility. Interventions targeting parents may thus appear promising. However, such interventions can only succeed if the relationship between parental risks and offspring outcomes are causal, which remains unclear. Here, we propose to use genetically informed design to better characterize the intergenerational pathways underlying risk transmission.
B3495 - 3D whole body scans - 06/04/2020
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.
B3498 - Body muscle and metabolism in middle age - 06/04/2020
Higher body fatness is a likely cause of heart disease, but how the harms of body fat compare with the potential benefits of body muscle â another metabolically active body compartment â is unclear. This project aims to use data on body scanning and metabolism from ALSPAC parents in mid-life to determine which aspects of body muscle â whether higher volume based on body scanning or higher strength based on hand grip tests â most strongly influence a set of detailed traits related to adult heart disease susceptibility. It also aims to determine how the cardiometabolic profile of body muscle compares with the profile of body fat. Together with results from complementary studies, these results should help clarify which aspects of body composition are most important to target with limited public resources in order to prevent the onset of heart disease.
B3499 - Characterising trajectories and transitions in tobacco nicotine and cannabinoid use and their relationship to mental health - 10/04/2020
Tobacco and cannabis use are key public health concerns. Both tobacco and cannabis are consistently associated with the development of common mental health disorders such as anxiety and depression. Prevalence of mental illness in the UK is rapidly increasing, and has increased particularly among adolescents and young adults. Tobacco and cannabis use appear to be plausible targets for intervention to improve mental health. However, there are a number of challenges that have hindered understanding of this relationship, and which have implications for how interventions should be targeted. Firstly, substance use and common mental disorders both tend to have onset in adolescence, so it is difficult to establish temporality in this relationship. Secondly, substance use and mental health share common risk factors through genes and early-life events, so it is difficult to establish whether the relationship is causal or due to shared confounding. Thirdly, the effect of substance use on mental health may not be a direct effect. It is plausible that this relationship is mediated by the social and economic adult role transitions following adolescence, or that substance use itself may be a mediating factor between early life exposures and mental health. Finally, the effects of the aforementioned changes in tobacco and cannabis products on substance use patterns and mental health are currently unknown.
We propose to investigate key questions regarding causality and opportunities for intervention in the relationship between tobacco use, cannabis use (and their constituents) and mental health.
B3491 - fasting insulin GWAS - 31/03/2020
A genome-wide association study of fasting insulin, proinsulin, glucagon, and Stumvoll insulin sensitivity index, and insulin fold change to identify the genetic architecture of these traits.
B3492 - Discovering the person behind the data Assembling and validating vulnerable childrens life histories from quantitative data - 27/04/2020
This proof of concept proposal (to ESRC Research Methods Development https://esrc.ukri.org/funding/funding-opportunities/esrc-rmdg-2020/), aims to test the validity of an innovative research approach bringing narrative/life history methods to quantitative longitudinal data, to deepen their explanatory power. Drawing on Singer et al (1998), the investigators have to date developed the method to yield insights (missing from aggregate analyses) into the impact of illness on womenâs employment trajectories (Holland, 2006), and counterintuitive aggregate findings that children and families receiving social work fare worse over time than similar others (Sharland et al, 2017).The validity of the approach now needs testing. If successful, it may be applied to multiple research questions and cohort/panel datasets, releasing narrative potential to discover the people behind the data and to explain complexity and change, especially in the absence of complementary qualitative longitudinal data.
Substantive focus will be on children with significant health-related difficulties as teenagers, exploring how these vulnerabilities are affected and affect their lives over time. A small sample of longstanding ALSPAC child, and unrelated parent, participants will be invited to: i) allow the research team to craft the child and familyâs life history from multiple variables collected directly from and/or administratively linked to the respondent over time; ii) participate in research interviews exploring the fit between their own and âresearch-assembledâ life story accounts; iii) permit analysis of this fit to be informed by further ALSPAC data mapped to their self-reports. Care will be taken to ensure informed consent and confidentiality throughout. If the inter-story compatibility is sufficiently strong, a scaled-up bid to a further ESRC call will follow.
B3490 - Neurodevelopmental Disorders and Cardiometabolic Risk in ALSPAC Cohort - 31/03/2020
Neurodevelopmental disorders (such as autism, ADHD, learning disability, and Tic Disorders) are lifelong conditions which begin in childhood and can have significant impacts on physical and mental health, and social well-being across the lifespan.
People with neurodevelopmental disorders have reduced life expectancy than people without such conditions (neurotypicals). Cardiovascular disease (such as heart attacks and strokes) is a significant contributor to this reduced life-expectancy. It is unclear why people with neurodevelopmental disorders are at increased risk of premature cardiovascular disease. Possible explanations include higher levels of cardiovascular risk factors (such as smoking, obesity, and physical inactivity) in people with neurodevelopmental disorders; difficulties in people with neurodevelopmental disorders accessing healthcare; and potentially shared biological mechanisms which contribute to causing both neurodevelopmental disorders and cardiovascular disease (such as over or under active immune systems).
This project aims to improve understanding of the association of neurodevelopmental disorders and cardiovascular disease. We aim to compare rates of cardiovascular risk factors (blood pressure, body mass index, cholesterol, glucose, insulin, and CRP- a measure of the immune system) and very early cardiovascular disease (as measured by the stiffness of arteries) between young adults (at aged 17 and 24) with neurodevelopmental disorders and without. We predict that young adults with neurodevleopmental disorders will have higher rates of both cardiovascular risk factors and very early cardiovascular disease when compared with neurotypical young adults. If this were to the case it would support a view that people with neurodevelopmental disorders are inherantly at increased risk of cardiovascular disease independent of their access to healthcare and would support policies for screening and early intervention in this group.
B3489 - Violent and nonviolent crime under the influence of alcohol - 27/03/2020
Strong associations exist between alcohol consumption and crime, but the extent to which these associations are causal is unclear. One hypothesised explanation is that the pharmacological effects of alcohol reduce cognitive capacity, and risk perception leading to an increased risk of committing a crime while under the influence of alcohol. We propose to examine the extent to which associations detected are causal using data collected at the ALSPAC focus clinic at age 24 years on committing crime while sober (which cannot be due to the situational effects of intoxication) and while under the influence of alcohol. We will examine the effects of alcohol consumption (prevalence, frequency, quantity) on violent and nonviolent crime, compare the association between drinking and engaging in crime while sober to the association between drinking and crime, and investigate whether cognitive factors (such as impulsivity, poor working memory and poor emotion recognition) increase the risk of crime while under the influence of alcohol.
B3488 - Mental health and educational outcomes in high-risk children - 02/04/2020
B3485 - Polygenic risk score prediction of BMI/adiposity/obesity in ALPSAC and longitudinal outcome data - 24/03/2020
B3486 - Mendelian randomisation analysis of the relationship between body composition BMI and related variables and Metabolon data - 24/03/2020
This work sits as part of a larger project to undertake a one sample MR analysis of the relationship between BMI and metabolon metabolite data in the Flemish Gut Fora Project.
The application here is to generate a training set of data for Wenxin (MSc student) from existing ALSPAC metabolon data. The aim here is to randomly select a sub-set of the ALSPAC BMI GRS Metabolon data - not for analytical/inferential worth, but for the purpose of allowing the student to develop scripts and analyses before getting hold fo FGFP data in full.
The proposal here would be fore direct users (included here) to randomly extract a sub-set of ALSPAC Metabolon data, to assign a random amount of error to that data set and to remove any ID reference from that data set. This dummy data set would then be used for the express purpose of understanding the format and nature of Metabolon metabolite data. Dr Hughs, Corbin or PhD student Matt Lee will be able to bring these data together (with a small set of relevant covariables). This should not generate burden for the ALSPAC data team.
B3487 - ALSPAC response to COVID-19 pandemic - 31/03/2020
In response to the COVID-19 pandemic we plan to send two standalone questionnaires out to ALSPAC participants to determine potential transmission (through questions on travel and symptoms) before the peak that is starting in the UK now. Exact content of the questionnaires is to be agreed but will also likely include measures of other symptoms (not just COVID but e.g. seasonal flu, anxiety), mental health (depression, well being), patterns of response to the pandemic (e.g. self isolating, working at home etc) and what indivdual's concerns are (financial, health, etc). We will follow up with our standard annual questionnaire to determine long term impact.