Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B3687 - Sensation-Seeking Related DNA Methylation and the Development of Delinquency A Longitudinal Epigenome-Wide Study - 12/01/2021

B number: 
B3687
Principal applicant name: 
Edward Dylan Barker | King's College London (United Kingdom)
Co-applicants: 
Jacintha Tieskens | PhD-student
Title of project: 
Sensation-Seeking Related DNA Methylation and the Development of Delinquency: A Longitudinal Epigenome-Wide Study
Proposal summary: 

Experiences of childhood maltreatment is suggested as an important risk factor for the development of delinquent behaviour. Heightened sensation-seeking is related to the development of delinquency. Moreover, sensation-seeking, or biological correlates of sensation-seeking, are suggested as factors linking childhood maltreatment to delinquency. More specifically, it is hypothesized that epigenetic correlates of sensation-seeking might function as a mechanism for translating environmental signals into biological changes that may subsequently lead to maladaptive behavior development. In this study we will try to identify the epigenetic correlates of sensation-seeking in children and investigate whether these epigenetic correlates are influenced by earlier experiences of childhood maltreatment and may impact subsequent development of delinquency in early adolescence.

Impact of research: 
Important information will become available on possible mechanisms of how adverse social experiences may become ‘under the skin’ and lead to maladaptive behavioural outcomes, such as delinquency. In addition, the role of sensation-seeking in the development of delinquency will become clearer and this information may help prevention programs to focus on important precursors of delinquent behaviour instead of intervene when delinquent symptoms are already present.
Date proposal received: 
Thursday, 17 December, 2020
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Epigenetics

B3695 - Genetic risk for Alzheimers disease and the metabolome across the life course - 12/01/2021

B number: 
B3695
Principal applicant name: 
Emma Anderson | University of Bristol
Co-applicants: 
Ms Hannah Compton, Dr Joshua Bell
Title of project: 
Genetic risk for Alzheimer’s disease and the metabolome across the life course
Proposal summary: 
Impact of research: 
informing other scientists about potential mechanisms of genetic risk for alzheimer's disease
Date proposal received: 
Tuesday, 5 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Epidemiology, Alzheimer's disease, Statistical methods, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B3679 - A Negative Control Analysis Investigating Maternal Smoking Alcohol consumption and BMI on Molar-Incisor Hypomineralisation - 12/01/2021

B number: 
B3679
Principal applicant name: 
Tom Dudding | University Hospitals Bristol (honorary: University of Bristol) (United Kingdom)
Co-applicants: 
Qui-Yi Lim, Kurt Taylor, Professor Deborah Lawlor
Title of project: 
A Negative Control Analysis Investigating Maternal Smoking, Alcohol consumption and BMI on Molar-Incisor Hypomineralisation.
Proposal summary: 

Molar-incisor Hypomineralisation (MIH) is a tooth condition specifically affecting the enamel (outer layer of the tooth) of one or more of the child’s first adult molars (back teeth) and in some cases the incisors (front teeth). MIH affected teeth appear discoloured, and vary in presentation; cream, yellow or brown. Teeth are commonly very sensitive, painful and in severe cases crumbly. Furthermore, affected teeth often have a poor prognosis and are more susceptible to dental decay meaning the teeth are often extracted before adulthood. It is usually diagnosed when the adult molars and incisors erupt in the mouth at around 6-7 years of age. In some cases, it can also affect the primary teeth, which is known as hypominersalised second primary molars (HSPM) and is seen around 2-3 years of age.

MIH has a high prevalence; approximately 13.1% globally (95% CI 11.8-14.5%) and 15.9% in the UK (95% CI 14.5-17.1%). The literature suggests MIH is caused by disturbances during tooth development. This is influenced by genetics and environmental factors, particularly during pregnancy, time of birth and in the first few years of life. Some of the environmental factors investigated include breastfeeding, environmental toxins (dioxins and Bisphenol A), problems occurring at birth and childhood illnesses. However, the literature concludes that the aetiology of MIH is unclear. Currently, there is little research on maternal factors and MIH, particularly the common environmental risk factors; maternal smoking (7 studies – the most recent suggesting a significant association) and alcohol consumption (2 studies), both in which the strength of evidence is weak and conflicting. Furthermore, much of the research conducted is retrospective and therefore prone common biases such as recall bias. There is a need for high-quality prospective studies. Other studies suggest that maternal smoking and alcohol consumption are associated with offspring HSPM. The embryological development of the second primary molars and first permanent molars are similar, and therefore may share the same environmental influences.

We propose to conduct a prospective study looking at the association between common maternal pregnancy characteristics and MIH. These include maternal smoking, alcohol consumption and body mass index (BMI). We will assess for the presence of residual confounding by including a negative parental exposure control. This involves comparing the confounder adjusted associations of maternal pregnancy exposures with the offspring outcome of interest to similarly adjusted associations of the same characteristics (negative controls) in the father. Similarly, we will use offspring dental trauma as a negative control outcome. Triangulating results from conventional multivariable regression, negative exposure controls and negative outcome controls provides scope to improve causal understanding.

Impact of research: 
Our results should help to improve our understanding on whether maternal smoking, alcohol consumption and BMI have an effect on MIH. This may help to provide accurate and non-stigmatised public health advice about maternal exposures and the dental health of children. As MIH affected teeth have been reported to have very poor prognosis and accounts for a significant proportion of childhood decay, diagnosing and intervening as early as possible can affect outcomes significantly. Understanding the risk factors may help to identify at-risk children and provide early intervention.
Date proposal received: 
Tuesday, 5 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Dentistry, Molar-incisor Hypomineralisation, Negative control, BMI, Development, Dental

B3697 - Investigating predictors of risk behaviours in adolescence and early adulthood - 12/01/2021

B number: 
B3697
Principal applicant name: 
Hannah Sallis | MRC IEU
Co-applicants: 
Prof. Marcus Munafo, Dr Zoe Reed, Dr Caroline Wright, Miss Agnes Kessling, Miss Ruby Richards
Title of project: 
Investigating predictors of risk behaviours in adolescence and early adulthood
Proposal summary: 

Identifying and understanding predictors of risky behaviour can help to inform prevention and intervention strategies for related outcomes. For example, alcohol consumption may have an influence on risky sexual behaviour, understanding this relationship could inform prevention and interventions for sexually transmitted diseases, unplanned pregnancies, abortions, and general sexual health. Another risk factor is for subsequent risk behaviours is adverse childhood experiences (ACEs). Individuals with histories of multiple ACEs are found to be more likely to engage in risk behaviours such as smoking, excessive drinking, risky sexual behaviour, illicit drug use and suicidal behaviour than those without.
This project will use longitudinal data from the ALSPAC study to identify predictors of risk behaviours in adolescence and early adulthood.

Impact of research: 
Date proposal received: 
Monday, 11 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Sexually transmitted diseases, chlamydia, gonorrhoea, Statistical methods, Childhood - childcare, childhood adversity, Offspring, Statistical methods

B3696 - Impact of immune sex differences in the first 1000 days of life - 12/01/2021

B number: 
B3696
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Co-applicants: 
Philip Goulder, Professor
Title of project: 
Impact of immune sex differences in the first 1000 days of life
Proposal summary: 

Substantial differences exist between the immune reponses made by males and females that critically impact health and survival. Typically, females make stronger immune responses to vaccines and infections and achieve superior outcomes throughout life. For example, females achieve the same levels of neutralizing antibodies from half the dose of influenza vaccine as males from the full dose. However, this more exuberant immune response leads to greater susceptibility to immunopathology and autoimmune diseases and more adverse events from immunizations. To complicate matters, there are exceptions; as fetuses, females have a 2-fold greater susceptibility to mother-to-child transmission of both HIV and HCV infection, and to IFN-I-resistant viruses. To better understand the mechanisms responsible for these complex observations, we propose to compare the epigenetic and hormonal responses in males and females to immunization and vaccination in early life. We hypothesize that life-long immune sex differences are established early through the interplay of host genetics, sex-specific steroid biosynthesis, epigenetics and the environment, and that early-life epigenetic changes in response to sex-specific steroid modulation and infection and immunization play a dominant role in this process.

Impact of research: 
In the short-term, we hope to better understand the mechanism responsible for sex-specific immune responses. In the long-term, improved understanding of these mechanisms should provide the rationale to tailor vaccines and treatments and improve patient outcomes.
Date proposal received: 
Thursday, 7 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Immunology, Infection, Microarrays, Proteomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics, Immunity, Sex differences

B3692 - Pregnancy complications menopausal symptoms and cardiovascular health - 06/01/2021

B number: 
B3692
Principal applicant name: 
Abigail Fraser | MRC IEU (United Kingdom)
Co-applicants: 
Title of project: 
Pregnancy complications, menopausal symptoms and cardiovascular health
Proposal summary: 

The link between women's reproductive and cardiovascular health is increasingly recognised. Some, but not all studies have shown that women who experience night sweats and/or hot flushes as part of the menopausal transition are more likely to have heart disease. We also know that women who have complications during pregnancy are at greater risk of heart disease later in life. Here we would like to investigate the associations between all of pregnancy complications, menopausal symptoms and cardiovascular health in a general population of women, the ALSPAC mothers. We will also use genetics data to examine whether genetic risk for for more adverse cardiovascular health are associated with pregnancy complications and/or vasomotor symptoms.

Impact of research: 
This study will improve our understanding of the nature of the relationship between pregnancy complications, VMMS and women's cardiovascular health.
Date proposal received: 
Tuesday, 22 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Epidemiology, DNA sequencing, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cardiovascular, Genetic epidemiology, Mothers - maternal age, menopause, obstetrics

B3691 - Influence of the month of birth on persistence of ADHD in prospective studies an individual patient data meta-analysis - 06/01/2021

B number: 
B3691
Principal applicant name: 
Stephan Collishaw | Cardiff University (United Kingdom)
Co-applicants: 
Thomas Broughton, Dr Kate Langley, Prof Kate Tilling, Professor Samuele Cortese, Corentin Gosling
Title of project: 
Influence of the month of birth on persistence of ADHD in prospective studies: an individual patient data meta-analysis
Proposal summary: 
Impact of research: 
The study will provide useful information for interpreting apparent low persistence of ADHD across development The study will likely lead to a high impact scientific publication The study will provide training and opportunity for international collaboration for a PhD student (project B3410)
Date proposal received: 
Saturday, 19 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Developmental disorders - autism, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Development, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3693 - Understanding the developmental associations between stress and self-harm - 06/01/2021

B number: 
B3693
Principal applicant name: 
Annekatrin Steinhoff | University of Zurich, Jacobs Center for Productive Youth Development (Switzerland)
Co-applicants: 
Title of project: 
Understanding the developmental associations between stress and self-harm
Proposal summary: 

Self-harm among adolescents and young adults is a widespread public health problem. Self-harm is often a maladaptive coping strategy used to alleviate severe emotion dysregulation following stressful events. Adolescence is a period of marked development in the realm of social relationships and socio-emotional competencies. However, the developmental associations between social stress and self-harm across the adolescent years are poorly understood. In particular, the mechanisms linking social stress and self-harm are largely understudied. Better knowledge about these processes is urgently needed, in order to identify promising targets for interventions designed to support adolescents with self-harm and help them cease from this self-destructive behavior.

Therefore, the aim of this project is to investigate how social stress and self-harm are interrelated between early adolescence and early adulthood. A particular focus will be on the mechanisms underlying these associations. Candidate mediators are a) biological manifestations of stress (e.g., inflammation) and b) physical health and health behaviors (e.g., sleep patterns). Potential gender differences will also be considered.

The findings will provide novel insights into the developmental precursors of adolescent self-harm and help improve intervention programs designed to reduce the enormous burden that self-harm can entail for individuals and society.

Impact of research: 
The findings will provide new insights into the mechanisms linking stress and self-harm, and inform a holistic understanding of the developmental antecedents and consequences of self-harm. The findings will also help identify youth at risk for self-harm and improve intervention programs designed to reduce the enormous burden that self-harm can entail for individuals and society.
Date proposal received: 
Sunday, 3 January, 2021
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B3689 - An individual participant data meta-analysis examining the associations between mode of delivery and respiratory outcomes - 06/01/2021

B number: 
B3689
Principal applicant name: 
Theodosia Salika | MRC LEU, University of Southampton (United Kingdom)
Co-applicants: 
Professor Hazel Inskip
Title of project: 
An individual participant data meta-analysis examining the associations between mode of delivery and respiratory outcomes.
Proposal summary: 

Systematic reviews and meta-analyses using aggregate data have indicated an increased risk of childhood asthma for women undergoing caesarean section, but the results were subject to moderate heterogeneity, potential residual confounding and publication bias1-4. We aim to use the EU child cohort network to re-examine the associations with different types of delivery using IPD MA to produce a more reliable pooled meta-analytic estimate. Potential mediators such as respiratory tract infections and allergic sensitization will be examined for the associations between different types of mode of delivery and asthma.

Impact of research: 
This will provide information about the association between mode of delivery and childhood asthma to inform policy about caesarean section usage.
Date proposal received: 
Friday, 18 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B3686 - LifeCycle How do early years risk factors mediate inequalities in child mental health and cognitive development - 06/01/2021

B number: 
B3686
Principal applicant name: 
David Taylor-Robinson | University of Copenhagen; University of Liverpool
Co-applicants: 
Dr Daniela Schlüter, Dr Katrine Strandberg-Larsen, Dr Angela Pinot de Moira, Anne-Marie Nybo Andersen, Gabriella Melis
Title of project: 
LifeCycle: How do early years risk factors mediate inequalities in child mental health and cognitive development?
Proposal summary: 

Reducing inequalities in child mental health is a public health priority, yet the pathways that link social conditions to mental health outcomes in the early years are unclear. Few studies have compared the social distribution and prevalence of mental health problems across countries, or have compared pathways to any inequalities. Understanding these pathways is critical in order to guide public policy to improve child health and reduce inequalities. In Life Cycle cohort families we aim to assess how early years risk factors mediate the relationship between childhood SECs and subsequent inequalities in child mental health and cognitive development.

Impact of research: 
Reducing inequalities in child mental health is a public health priority, yet the pathways that link social conditions to mental health outcomes in the early years are unclear. Few studies have compared the social distribution and prevalence of mental health problems across countries, or have compared pathways to any inequalities. Understanding these pathways is critical in order to guide public policy to improve child health and reduce inequalities.
Date proposal received: 
Tuesday, 5 January, 2021
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Epidemiology

B3694 - Epigenome-wide association study of handedness - 06/01/2021

B number: 
B3694
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Co-applicants: 
Veronika Odintsova
Title of project: 
Epigenome-wide association study of handedness
Proposal summary: 

Hand preference is only weakly determined by genetics. Consequently, environment likely plays a role by modifying the expression of certain genes during early development. In this study, we will ask to what extent DNA methylation, a well-known regulator of genes, is associated with hand preference in ALSPAC children and their parents beyond known genetic associations.

Impact of research: 
Improved understanding of the relationship between DNA methylation and handedness.
Date proposal received: 
Monday, 4 January, 2021
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Developmental biology, hand preference, Microarrays, Development, Epigenetics, Handedness

B3690 - Epigenetic prediction of pubertal timing - 06/01/2021

B number: 
B3690
Principal applicant name: 
Peter Tanksley | University of Texas at Austin (United States)
Co-applicants: 
Kathryn Paige Harden, PhD, Elliot Tucker-Drob, PhD, Laurel Raffington, PhD
Title of project: 
Epigenetic prediction of pubertal timing
Proposal summary: 

Puberty is a time of sweeping biological and social change. Boys and girls who experience early and/or rapid puberty are at elevated risk for psychiatric and physical health problems, including substance use disorders, suicide, polycystic ovary syndrome (in females), and cardiovascular disease. Psychiatric disorders like major depressive disorder also become much more prevalent at puberty and may impede cognitive skill development . Considering the many negative implications of departures from the normal pubertal development, understanding the genetic and environmental regulators of puberty has become a topic of increasing urgency. Our research aims to identify specific and potentially modifiable environmental factors that influence pubertal timing and examine its association with children’s cognitive development and mental health, and we view genetic and epigenetic data as essential tools for accomplishing that goal.

Scientific progress on understanding genetic influences and epigenetic changes (including DNA methylation) at puberty has moved slowly. Previous studies looking at changes in DNA methylation across puberty have been conducted in very small samples; nevertheless, this previous work support the potential to develop an epigenetic clock for pubertal age, analogous to epigenetic clocks that exist for aging. However, generating a clock that is highly accurate and robust requires longitudinal DNA methylation data spanning the pubertal transition. We will substantially improve the rigor and reproducibility of previous research on the epigenetics of pubertal age by using a discovery sample that is substantially better-powered (the Texas Twin project) and by replicating results in an independent sample (ALSPAC). We can then examine potential environmental (e.g., family socioeconomic background) and genetic predictors (e.g., polygenic scores of reproductive phenotypes) of our epigenetic clock for pubertal age, as well as the cognitive and mental health sequelae of advanced epigenetic pubertal age.

Impact of research: 
We believe this research will have impact in at least three ways. First, this research will create a better understanding of how environments, genetics, and epigenetics work together to shape pubertal development. Second, this research will provide a biomarker of pubertal age that will be a useful resource for future research. Third, this research will contribute to a better understand of the mechanisms underlying and modifying adverse experiences around the pubertal transition.
Date proposal received: 
Friday, 18 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Puberty

B3685 - Diagnostic prediction model for coeliac disease - 06/01/2021

B number: 
B3685
Principal applicant name: 
Martha Elwenspoek | University of Bristol (United Kingdom)
Co-applicants: 
Penny Whiting
Title of project: 
Diagnostic prediction model for coeliac disease
Proposal summary: 

Coeliac disease (CD) is an autoimmune disorder, triggered by the protein gluten, and affects 1% of the UK population. Some patients with CD may be asymptomatic, others present with non-specific symptoms, making the diagnosis difficult. Only 30% are thought to be diagnosed. Treatment for CD is lifetime adherence to a gluten free diet. Untreated CD may lead to malnutrition, anaemia, osteoporosis, infertility in women, lymphoma and small bowel cancer. Guidelines recommend that adults and children “at high risk” of CD should be offered testing. However, it is not clear which groups are at sufficiently high risk to justify routine testing.
We have performed a systematic review to identify symptoms and risk factors related to CD. We will use ALSPAC data from children who were tested for CD to determine which combination of symptoms and risk factors best predict CD diagnosis. The results from this study may help GPs decide who should be offered testing for CD.

Impact of research: 
Appropriate identification and treatment of CD can have significant benefits for patients in terms of symptoms, quality of life, and long-term health outcomes, as well as reducing healthcare and societal economic costs.
Date proposal received: 
Thursday, 17 December, 2020
Date proposal approved: 
Thursday, 17 December, 2020
Keywords: 
Epidemiology, Coeliac disease, Computer simulations/modelling/algorithms, Statistical methods, Coeliac disease

B3681 - From Social Cognitive Deficits to Later Emotional and Behavioural Problems The Roles of Cortisol and Inflammatory Cytokines - 17/12/2020

B number: 
B3681
Principal applicant name: 
Marta Francesconi | University College London (UK)
Co-applicants: 
Dongying Ji, Ms, Steven Papachristou, Eirini Flouri
Title of project: 
From Social Cognitive Deficits to Later Emotional and Behavioural Problems: The Roles of Cortisol and Inflammatory Cytokines
Proposal summary: 

Social cognition, the ability to understand the mind of other people, is essential for successful social
interaction. Children with emotional and behavioural problems are more likely to have a history of poor
social cognition ability. However, the path from poor social cognition to emotional and behavioural problems
in childhood and adolescence is unclear. The possibility I will explore in this PhD project is that social
cognitive deficits increase stress (i.e., hypothalamus-pituitary-adrenal dysregulation and flattened cortisol
rhythm and/or chronic inflammation), leading to emotional and behavioural problems. Cortisol and
inflammatory cytokines are thought to be promising biomarkers of various stressed-related behavioural and,
particularly, emotional disorders, yet existing evidence in children and adolescents is little and mixed, and
is mostly about clinical disorders. Additionally, it is not known yet how cortisol and inflammatory cytokines
work when facing stress caused by social cognition deficits, especially in the general population. The aim
of the project is to explore the role of these biomarkers in the interplay mechanism of social cognition deficits
and emotional and behavioural problems in children and adolescents, using longitudinal data from a large
general population study, the Avon Longitudinal Study of Parents and Children. Analytically, the project will
explore three relationships: a) the longitudinal association between deficits in core aspects of social
cognition (emotion recognition & theory of mind) and emotional and behavioural problems, b) the role of
cortisol in explaining the association and c) and the role of inflammatory cytokines in explaining the
association. The relationship between inflammation and cortisol is complex so the final analysis exploring
the role of both will consider this complexity fully.

Impact of research: 
Academic and policy. We think our findings will be of use and value to the following 4 groups. The first group are those making decisions about preventive and early treatment interventions. A second group to whom results will be addressed are the general public, especially parents and expectant parents. Academic researchers are a third category of users, including those with a substantive interest in child emotional and behavioural development, those interested in stress ‘effects’ and those interested in advanced longitudinal modelling. Finally, we hope to inform those commissioning research in child development, who, to a large extent, continue to underestimate or neglect the interaction between the body and the mind.
Date proposal received: 
Tuesday, 15 December, 2020
Date proposal approved: 
Thursday, 17 December, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Statistical methods, Birth outcomes, BMI, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Immunity, Intelligence - memory

B3680 - NCS Cohort Project ARQ1 COVID-19 and Mental Health Outcomes - 16/12/2020

B number: 
B3680
Principal applicant name: 
Gareth Griffith | University of Bristol (UK)
Co-applicants: 
Dr Jazz Croft, Dr Alex Kwong, Dr Ruth Mitchell, Dr Kate Northstone, Professor Nic Timpson
Title of project: 
NCS Cohort Project, ARQ1, COVID-19 and Mental Health Outcomes
Proposal summary: 

The COVID-19 pandemic has affected daily life across the UK from early March 2020. Viral suppression measures, including nationwide social distancing laws and the imposition both local and national lockdowns are likely to have had a large scale but heterogeneous impact on individual mental health outcomes over this period. Research published using ALSPAC COVID-19 questionnaire data has suggested that whilst depressive symptoms did not increase amongst respondents, anxiety symptoms increased considerably (Kwong et al. 2020). The distribution of these effects are currently poorly understood. This project aims to contextualise how individuals' mental health has changed over the course of the pandemic, and how subsequent economic and health outcomes have been moderated by prior mental health difficulties. Understanding how existing inequalities in mental health prevalence interact with, and are amplified by, the pandemic and associated viral suppression measures is of critical public health importance in helping to identify vulnerable groups in need of further support to aid in reducing health inequalities and promote wellbeing.

Using data from Children of the 90s, we can investigate participants' mental health status, employment, housing, and health behaviours before and during the pandemic, to enable us to make inference about mental health impacts conditional on prior health status.

Impact of research: 
Findings will contribute to the limited evidence base of the impacts of COVID-19 and viral suppression measures on mental health outcomes. It will help target funding at those most vulnerable to the negative outcomes of the pandemic, and inform the need for nuanced mental interventions to alleviate adverse impacts of viral suppression measures.
Date proposal received: 
Tuesday, 15 December, 2020
Date proposal approved: 
Wednesday, 16 December, 2020
Keywords: 
Epidemiology, Mental health, Statistical methods

B3677 - Does sleep quality and quantity during the early years having lasting effects on educational outcomes - 06/01/2021

B number: 
B3677
Principal applicant name: 
Amy Atkinson | Centre for Applied Education Research (United Kingdom)
Co-applicants: 
Dr Lisa Henderson, Professor Gareth Gaskell, Dr Liam Hill, Professor Mark Mon-Williams
Title of project: 
Does sleep quality and quantity during the early years having lasting effects on educational outcomes?
Proposal summary: 

Several studies have demonstrated that sleep during the early years (i.e. prior to formal school entry) can predict later language skills, cognition and wellbeing during childhood and adolescence. However, these studies have typically only examined a few sleep parameters (e.g. Dionne et al., 2011; Knowland et al., in press;), with some mixed findings emerging (Kocevska et al., 2017; Touchette et al., 2007). Moreover, research exploring the effects on later mental wellbeing have generally relied on a composite ‘sleep problems’ variable (reflecting various individual sleep parameters; e.g. frequent wakings, early wakings, nightmares; e.g. Gregory & O’Connor, 2002), making it difficult to conclude which sleep parameters are important. Further research is therefore needed to systematically examine the effects of early sleep on these critical cognitive and wellbeing outcomes. Nevertheless, based on existing evidence, it appears that sleep quality and quantity parameters can predict key outcomes during childhood and adolescence.

However, the effects of early sleep have only been considered on a limited number of outcomes to date. Notably, extant investigations into the effects of sleep on cognitive outcomes have relied on standardised test performance. It is therefore unclear whether early sleep parameters predict real-world cognitive outcomes, such as educational performance. Although there is evidence that sleep parameters are predictive of school readiness and academic achievement (e.g. Drake et al., 2003; Tso et al., 2016), these studies have either been cross-sectional in nature (measuring sleep close in time to the educational assessments) or longitudinal studies that commenced at or after the point of school entry. Longitudinal investigations of the effects of early sleep (i.e. before school entry) on later educational outcomes are lacking. The planned research will address these questions, by examining whether sleep during early development (i.e. at 6-42 months of age) predicts performance on a school entry assessment and academic achievement.

The project will also investigate factors that drive the effects of early sleep on later educational outcomes. As school readiness and academic achievement are closely linked to language abilities, cognitive skills, and mental wellbeing (e.g. Agnafors et al., 2020; Duncan et al., 2007; Romano et al., 2010), these factors may mediate the relationship between early sleep and educational outcomes. Alternatively, or additionally, it is possible that the longitudinal effects on educational outcomes may be driven by persistent sleep patterns. Indeed, there is some evidence that sleep parameters show continuity throughout childhood and adolescence (e.g. Stein et al., 2001). As such, it is possible that early sleep patterns may predict sleep parameters measured close in time to the school readiness and academic assessments, with sleep at these latter timepoints affecting educational performance. The current research will investigate these research questions by: (i) further examining how early sleep relates to language, cognitive, and wellbeing outcomes at school entry; and (ii) investigating whether these factors drive the relationship between early sleep and later educational outcomes.

Finally, from both a theoretical and practical perspective, the project will examine whether effects of sleep are equivalent for different groups of children. As cross-sectional studies have found that sleep is particularly important for cognitive functioning and academic outcomes in children from disadvantaged backgrounds (e.g. Wetter et al., 2019), this analysis will focus on examining whether the longitudinal effects of early sleep are moderated by maternal education and self-reported financial difficulties.

Impact of research: 
This work will have important theoretical implications by delineating the extent to which early sleep predicts performance on meaningful assessments of school readiness and academic achievement. It will provide further insights into the effects of early sleep on later language skills, cognitive abilities, and mental wellbeing. The work may also be important practically, potentially identifying a novel way in which educational outcomes and mental wellbeing can be enhanced during childhood and adolescence. Furthermore, by investigating whether the effects of early sleep are particularly pronounced in children from disadvantaged backgrounds, this project might identify a novel way in which the socioeconomic status gap in educational performance could be reduced.
Date proposal received: 
Saturday, 12 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Social Science, Cognitive impairment, mental health - e.g. anxiety, depression, psychosis, etc, speech/language problems, Statistical methods, • Childhood - childcare, childhood adversity • Cognition – cognitive function • Communication (including non-verbal) • Development • Sleep • Speech and language

B3676 - NCS ARQ6 Identifying cases of COVID-19 in the ALSPAC cohort - 15/12/2020

B number: 
B3676
Principal applicant name: 
Kate Northstone | University of Bristol (United Kingdom)
Co-applicants: 
Professor Nic Timpson, Ruth Mitchell
Title of project: 
NCS ARQ6: Identifying cases of COVID-19 in the ALSPAC cohort
Proposal summary: 
Impact of research: 
Provide a resource for other cohort studies to assist them in identifying cases.
Date proposal received: 
Friday, 11 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Epidemiology, Infection, Immunity

B3674 - Childcare attendance and age of introductions on respiratory infections allergy and asthma - 15/12/2020

B number: 
B3674
Principal applicant name: 
Rachel Foong | Telethon Kids Institute (Australia)
Co-applicants: 
Professor Graham Hall, Associate Professor Rae-Chi Huang
Title of project: 
Childcare attendance and age of introductions on respiratory infections, allergy and asthma
Proposal summary: 

Studies examining the effects of attendance at childcare on the development of asthma are conflicting. There are studies that report a protective effect, no effect and an increased risk of respiratory symptoms and allergic disease. Risks associated with asthma are however influenced by age of childcare attendance and family history of asthma. Children attending childcare also have more frequent infections than those who stay at home, and infections are a known risk factor for asthma. This study aims to investigate if attendance at childcare is associated with increased risk of allergies and asthma, and if the age of introduction and respiratory infections play a role.

Impact of research: 
In the Lifecycle consortium, we will be available to better determine the effects of early childcare attendance on respiratory outcomes in Europe, the UK and Australia with more certainty given the large sample size.
Date proposal received: 
Thursday, 10 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Physiology, Allergy, Infection, Respiratory - asthma, Statistical methods, Childhood - childcare, childhood adversity

B3675 - Myopia in Young Adults - 15/12/2020

B number: 
B3675
Principal applicant name: 
Jeremy A. Guggenheim | School of Optometry & Vision Sciences Cardiff University (United Kingdom)
Co-applicants: 
Dr Cathy Williams, Professor Ian Flitcroft, Professor Stan Zammit, Professor Russ Jago, Professor Peter Blair, Dr Anna Pease
Title of project: 
Myopia in Young Adults
Proposal summary: 

Myopia (short-sightedness) is an eye condition in which distance vision is blurry. People with myopia need to wear glasses or contact lenses, or have laser refractive surgery, to achieve sharp distance vision. When people with myopia get older, they are at a higher-than-average risk of developing permanent sight problems such as macular disease. Myopia typically develops during school age. The reason it develops is not understood, however both genes and lifestyle factors are known to play a role. Children whose parents have myopia inherit a genetic predisposition to develop myopia themselves. In clinical studies, children who are randomly assigned to spend extra time outdoors each day have a lower incidence of myopia, suggesting that spending too little time outdoors is a risk factor. Individuals who spend more years at school also tend to develop a higher level of myopia. Around the world, the prevalence rate of myopia varies widely. This is thought to be related to the variation in the ‘intensity’ of school work and the pressure to do well at school. Myopia has also been linked to mental health problems such as depression and to levels of physical activity. However, for most of these links, it is unclear if myopia is a cause or a consequence of the association.

The ALSPAC cohort is unique in the scale and breadth of the information that has been collected about vision problems in childhood. This includes information about myopia development. In previous studies of ALSPAC participants, our research group has documented the time-course of myopia development and exposure to risk factors or protective factors such as time spent outdoors. For example, children from the ALSPAC cohort who spent relatively less time outdoors than their peers at age 7-years-old were found to have an increased risk of developing myopia by the age of 15. Here, we propose to build on our previous findings. Our primary aim is to discover if myopia is the cause or consequence of its associations with other lifestyle factors and health or wellbeing characteristics. To do this, we will use a technique called Mendelian randomisation, which uses random inheritance of subtle genetic features in a way similar to randomisation of participants in a clinical trial. Usually, Mendelian randomisation studies require very large cohorts of participants – larger than the ALSPAC cohort. However, myopia and many of the related conditions we plan to investigate are highly heritable, which means there is a good prospect of successfully answering our research questions using data collected in a sample the size of the ALSPAC cohort. Our secondary aims are extensions of the primary aim. We will compare the eye characteristics and lifestyle of children growing up in the UK with those of children elsewhere, to investigate if the risks for myopia are similar or different in countries with high or low prevalence rates of myopia. We will also extend our previous studies into the genetics of myopia. The exceptionally high level of detail that the ALSPAC research team has collected about genetics will allow us to test the role of specific genes in conferring a predisposition to myopia, and how this varies depending on the lifestyle risk factors that children are exposed to.

Impact of research: 
As regards lifestyle risk factors, we will seek to confirm previous observational associations and, where possible, use Mendelian randomisation to assess the direction of causality. The findings may aid the design of future randomised controlled trials for interventions designed to reduce myopia progression. As regards genetic risk, our studies may help identify novel genes that confer a risk of myopia. This knowledge may aid the development of drugs capable of slowing myopia progression.
Date proposal received: 
Thursday, 10 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Ophthalmology, Gene mapping, GWAS, Microarrays, RNA, Statistical methods, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Mendelian randomisation, Physical - activity, fitness, function, Sleep, Vision

B3671 - Urban exposome during pregnancy and early childhood and child cognitive and motor function - 15/12/2020

B number: 
B3671
Principal applicant name: 
Monica Guxens | ISGlobal
Co-applicants: 
Anne-Claire Binter
Title of project: 
Urban exposome during pregnancy and early childhood and child cognitive and motor function
Proposal summary: 
Impact of research: 
Date proposal received: 
Tuesday, 15 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Epidemiology, Cognitive impairment, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Cognition - cognitive function, Statistical methods

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