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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B3748 - Data collection measurement and correlates of internalized weight stigma - 29/04/2021

B number: 
B3748
Principal applicant name: 
Amanda Hughes | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Prof Laura Howe, Dr Helen Bould
Title of project: 
Data collection: measurement and correlates of internalized weight stigma
Proposal summary: 

Increasing evidence suggests that social processes including weight-related stigma are key to explaining many consequences of overweight and obesity. For instance, people carrying genetic variants linked to obesity are at higher risk of depression, even where those variants have no known metabolic consequences(1). This strongly implicates social, not just biological, processes by which body weight affects mental health. Among the different facets of stigma is internalized weight stigma (self-attribution of negative obesity-related stereotypes) which may have especially negative consequences. For higher-weight individuals, it is linked to disordered eating(2), maladaptive coping(3), and worse quality of life(4). But it can also affect normal weight and underweight people, and predicts disordered eating and drive for thinness in non-overweight groups(5).
Despite strong theoretical work in this area, our empirical understanding of weight stigma’s causes and consequences is limited. This includes how socioeconomic factors, adiposity development across the lifecourse, and parental body weight influence weight stigma internalization, and the consequences for mental health and social functioning. This is because research has been almost entirely based on small, non-representative samples. In this project, we would measure internalized weight stigma among ALSPAC participants of all weight statuses using a validated questionnaire(6). This would, uniquely, allow investigation of its causes and consequences in a large sample of young people. We would also investigate if a proxy measurement of internalized weight stigma can be constructed from other items, for when purpose-designed items are unavailable. The data and results will support further research in a range of existing data sources.

Impact of research: 
The analysis of causes and consequences of internalized weight stigma within ALSPAC will be a step-change in this area. Research has so far been restricted to small samples, often highly non-representative, and usually with only self-reported height and weight information. The exploration of a possible proxy measure for internalized weight stigma, meanwhile, will support further analysis in national surveys including the Millennium Cohort Study and the UK Household Longitudinal Survey, both of which include the proxy item but not the validated measure of internalized weight stigma. In this way, analysis on internalized weight stigma would be facilitated in nationally representative populations across the adult range, in surveys with a considerable ethnic minority population, and in surveys where genetic and linked administrative data would support application of causal inference methods and avoidance of reporting bias.
Date proposal received: 
Monday, 22 March, 2021
Date proposal approved: 
Monday, 22 March, 2021
Keywords: 
Epidemiology, Eating disorders - anorexia, bulimia, Mental health, Obesity, Statistical methods, BMI, Childhood - childcare, childhood adversity, Psychology - personality, Social science

B3721 - Perinatal and postnatal risk factors for mental health symptoms in adolescence - 15/03/2021

B number: 
B3721
Principal applicant name: 
Steven Marwaha | University of Birmingham
Co-applicants: 
Camilla Carr, Cristina Preece, Dr Isabel Morales Muñoz
Title of project: 
Perinatal and postnatal risk factors for mental health symptoms in adolescence
Proposal summary: 

Perinatal psychiatry is a relatively new, multidisciplinary field of psychiatry. Perinatal usually refers to the period immediately before and after birth, starting at the 20th to 28th week of gestation and ending 1 to 4 weeks after birth; while the postnatal period can be defined as the first 6-8 weeks after birth. Although knowledge is increasing, more research is needed to clarify the associations between parental and offspring mental illness.
The theory behind the potential associations between perinatal and postnatal risk factors and subsequent offspring mental health problems proposes that environmental stress, during pregnancy, such as life event exposure, may affect the neurodevelopment of the foetus and lead to an increased risk of psychopathology.
Among the perinatal and postnatal risk factors that have been investigated in the last years, maternal postnatal depression is one of the most relevant and studied risk factors, and thus most of the existing research is solely focused on this specific risk factor. Further, maternal postnatal depression is known to have an adverse effect on several aspects of child and adolescent development, including social, emotional, and cognitive function, and is associated with offspring depressive symptoms in adolescence and adulthood. Maternal postnatal depression might negatively affect bonding and parenting during infancy, which might affect offspring attachment style and increase the risk of psychotic experiences, among others.
In addition to postnatal depression, there are some other perinatal and postnatal risk factors that could be considered a form of psychological distress and that might reflect chronic maternal stress, which could affect the neurodevelopment of offspring. Among these risk factors, perinatal and postnatal maternal sleeping problems, family adversity, substance abuse, gestational age, or maternal age when birth could also play an important role in the development of subsequent mental health problems in adolescence, such as depressive and psychotic symptoms. However, to the best of our knowledge, this is the first study investigating a range of relevant perinatal and postnatal risk factors for subsequent psychopathology in adolescence.

Impact of research: 
This research will provide novel information about the role of perinatal and postnatal risk factors for the development of offsprings depressive and psychotic symptoms in adolescence.
Date proposal received: 
Thursday, 11 March, 2021
Date proposal approved: 
Monday, 15 March, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health

B3738 - Gestational Age at Birth and Childhood Body Size - 15/03/2021

B number: 
B3738
Principal applicant name: 
Anne-Marie Nybo Andersen | University of Copenhagen (Danmark)
Co-applicants: 
Johan Lerbech Vinther, Phd Student
Title of project: 
Gestational Age at Birth and Childhood Body Size
Proposal summary: 

Preterm birth and overweight constitutes
significant global burdens at individual and structural level underlining an
importance
for identifying modifiable risk factors to inform preventive efforts, e.g. in early-life.
It is well-established that birth weight is associated with later increased risk of
adiposity, and it has been suggested that gestational age is the factor behind this
association. Still, evidence is scarce and social context may affect the association

Impact of research: 
This reasearch will add to the literature evidence on the impact of gestational age on offspring body size in the first 18 years of life. Also, findings from this cross-cohort study will add important information about geographical variations in this association
Date proposal received: 
Monday, 15 March, 2021
Date proposal approved: 
Monday, 15 March, 2021
Keywords: 
Epidemiology, Obesity, Statistical methods, BMI, Metabolic - metabolism, Offspring, Statistical methods

B3735 - Financial Stress and Smoking Behaviour - 15/03/2021

B number: 
B3735
Principal applicant name: 
Marcus Munafo | The University of Bristol
Co-applicants: 
Dr Alex Kwong , Henry Shirlaw
Title of project: 
Financial Stress and Smoking Behaviour
Proposal summary: 

Smoking is the leading cause of preventable death in the UK (Cornish et al., 2019) and represents both a risk of serious illness (Prescott, 2019; Bello et al., 2014) and a significant burden on public services and the economy (Ekpu and Brown, 2015). As a result, research which may have potential implications for smoking cessation interventions may be considered justified.

A number of studies have examined the relationship between financial stress and smoking behaviour and identified associations between these variables (Guillaumier et al., 2017; Siahpush, Borland and Scollo, 2013). However, the exact causal nature of this relationship may be considered somewhat obscure.

The proposed research plans to investigate the possibility of financial stress acting as an active predictor/risk factor of smoking behaviour. The longitudinal nature of the ALSPAC data facilitates research examining how changes in financial stress overtime may relate to later smoking behaviour. Although exact cause and effect may not be identified, tracking the relationship between these variables overtime may offer some form of greater insight into how they interact. This insight may be considered enough to make recommendations for further investigation and/or have implications for smoking cessation interventions.

Impact of research: 
This research may potentially inform us about if/to what extent we consider financial stress as an active predictor/risk factor of smoking. This subsequently may have potential implications for how addressing financial stress may be considered when applying smoking cessation interventions.
Date proposal received: 
Wednesday, 10 March, 2021
Date proposal approved: 
Monday, 15 March, 2021
Keywords: 
Health Services Research/Health Systems Research, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc.

B3736 - Lifecycle The role of maternal eating disorders in childhood wheezing asthma and lung function - 15/03/2021

B number: 
B3736
Principal applicant name: 
Maja Popovic | University of Turin, Department of Medical Sciences (Italy)
Co-applicants: 
Prof Lorenzo Richiardi
Title of project: 
Lifecycle: The role of maternal eating disorders in childhood wheezing, asthma and lung function
Proposal summary: 

Maternal mental disorders have been shown to influence foetal development, increase the risk of pregnancy complications, and the risk of several perinatal and childhood outcomes, including wheezing and asthma. To date asthma research has been predominantly focused on the most frequent mental disorders, such as depression and anxiety, showing that these two disorders and broadly-defined maternal stress increase the risk of childhood respiratory diseases, most likely through the activation of the hypothalamic-pituitary-adrenal axis. The low prevalence of eating disorders, especially during pregnancy, makes challenging single study analyses, and collaborative projects that involve birth cohorts with prospectively collected data represent the best setting for elucidating the association between maternal eating disorders and childhood respiratory outcomes. In this project we will estimate the associations of maternal lifetime eating disorders with childhood preschool and school-age wheezing and asthma, and with childhood/adolescent lung function in several cohorts participating in the EU Child Cohort Network.

Impact of research: 
Eating disorders are characterized by severe disturbances in eating behavior that significantly impact an individual’s emotional, psychosocial and physical well-being. The literature suggests that maternal eating disorders negatively influence child growth, feeding behaviors, cognitive and psychological development, while less is known on childhood respiratory outcomes. This study will add to the existing knowledge on the associations between maternal eating disorders and childhood outcomes and increase the knowledge on the effect of eating disorders independent of other mental health comorbidities, including depression and anxiety. We aim to move forward and explore the potential mediating pathways, focusing in particular on some modifiable factors during early childhood, including breastfeeding and daycare attendance.
Date proposal received: 
Wednesday, 10 March, 2021
Date proposal approved: 
Monday, 15 March, 2021
Keywords: 
Epidemiology, Respiratory - asthma, Asthma, Wheezing, Eating disorders, Mental health

B3729 - Growing up in deprivation or threat A network decision tree approach to the timing of early adversity - 12/03/2021

B number: 
B3729
Principal applicant name: 
Duncan Astle | University of Cambridge (United Kingdom)
Co-applicants: 
Sofia Carozza, Dr Joni Holmes
Title of project: 
Growing up in deprivation or threat: A network decision tree approach to the timing of early adversity
Proposal summary: 

Early life adversity can have a profound impact on children's cognitive development. But is that association specific or general? We want to test whether adversities group according to their type, and whether the longitudinal impact of different types of adversity are associated with different kinds of negative outcome.

Impact of research: 
Date proposal received: 
Monday, 8 March, 2021
Date proposal approved: 
Friday, 12 March, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity

B3728 - Assessing individual susceptibility to changes in sleep during the COVID-19 lockdown - 12/03/2021

B number: 
B3728
Principal applicant name: 
Rebecca Richmond | University of Bristol (United Kingdom)
Co-applicants: 
Miss Bryony Hayes
Title of project: 
Assessing individual susceptibility to changes in sleep during the COVID-19 lockdown
Proposal summary: 

Stay-at-home orders during the COVID-19 pandemic have had a major impact on people's usual routines, including their sleeping patterns. Recent studies have demonstrated that relaxed work schedules and more time spent at home have meant that the timing of sleep has become more regular, with less "social jetlag" (the discrepancy in sleep timing between working and non-working days) (1). Nonetheless, there are also been reports in a decline in sleep quality based on self-reported data (2). The factors which influence individual's susceptibility to altered sleep patterns during the pandemic have not been fully investigated. Within the Avon Longitudinal Study of Parents and Children (ALSPAC), parents and young people (YP) were asked to report whether their amount of sleep had decreased, stayed the same, or increased during lockdown. They were also asked to record any difficulty sleeping.

References:
(1) Christine Blume, Marlene H. Schmidt, Christian Cajochen. Effects of the COVID-19 lockdown on human sleep and rest-activity rhythms. Current Biology, 2020; DOI: 10.1016/j.cub.2020.06.021
(2) Kenneth P. Wright, Sabrina K. Linton, Dana Withrow, Leandro Casiraghi, Shannon M. Lanza, Horacio de la Iglesia, Celine Vetter, Christopher M. Depner. Sleep in University Students Prior to and During COVID-19 Stay-at-Home Orders. Current Biology, 2020; DOI: 10.1016/j.cub.2020.06.022

Impact of research: 
Identifying lifestyle or genetic predictors of changes in sleep during lockdown, could be useful for identifying or risk-stratifying those individuals most susceptible to sleep disruption.
Date proposal received: 
Tuesday, 9 March, 2021
Date proposal approved: 
Friday, 12 March, 2021
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Sleep traits such as insomnia and sleep duration, GWAS, Statistical methods, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Sleep, Statistical methods

B3737 - The CIVIC project Predicting Covid-19 Impact on Vulnerable Individuals and Communities via Health and Loyalty Card data - 19/03/2021

B number: 
B3737
Principal applicant name: 
James Goulding | University of Nottingham (United Kingdom)
Co-applicants: 
Prof Nic Timpson , Prof Markus Owens, Dr Anya Skatova, Dr John Harvey, Prof Chris Starmer, Prof Andrew Smith
Title of project: 
The CIVIC project: Predicting Covid-19 Impact on Vulnerable Individuals and Communities via Health and Loyalty Card data
Proposal summary: 

Diseases such as COVID-19 are not defeated, and there remains an urgent need for improved modelling of disease incidence to support future early-warning systems; improved prevalence estimation; and understanding of long term impacts to vulnerable communities. Finding data to underpin such analyses, however, is extremely difficult indeed. Much COVID incidence goes completely unreported; even the largest studies are limited to tiny fractions of the population, and biased towards specific demographics; and generalized studies have to use either tip-of-the-iceberg medical statistics (ONS, NHS), fine-grained but unsustainable self-reporting technologies (e.g. KCL’s COVID Symptom Study app), or broad brush behavioural data (e.g. Google COVID-19 mobility reports, Social media data). With a lack of widespread adoption of track-and-trace systems in the UK, and (understandably) declining public engagement with self-reporting initiatives, new approaches are urgently required.

A solution is available however. Epidemics such as COVID-19 are now well recognized as being driven as much by behavioural factors as they are from clinical ones - behavioural factors that are richly embedded in the mass, anonymized retail transaction logs held (untapped) in CIVIC's private-sector partners' datasets. Through the interrogation of such data (e.g. health purchases from the UK's leading health retailer), CIVIC will address key epidemiological knowledge gaps in: determining dynamic estimates of untested COVID-19 via fine-grained pharmacy and self-medication datasets; advancing AI/Modelling knowledge by triangulating behavioural features embedded in >1.5 billion loyalty-card logs - that can act as predictors of future outbreak; and advancing the state-of-the-art in identification and mapping of key vulnerable communities across the UK (Olio, Fareshare, ONS).

In such modelling "ground-truth" labelling of target (independent) variables) is crucial. In stage 1 of CIVIC, analysis will occur at aggregated LSOA geographical levels, with data-points labelled with (a) time series of recorded incidence in each LSOA (NHS) and (b) time series of relevant 111-related activity. However in Stage-2, CIVIC will importantly, also investigate the potential of "data-linkage", an approach that holds potential to underpin finer-grained individual level analyses at scale. Such processes must be engrained with privacy-by-design, and underpinned by informed and participatory consent, if they are ever to contribute to public health.

Impact of research: 
The aim, and target impact, of this research is 3-fold: 1. To establish the potential of behavioural signals (held in mass, and readily anonymizable, transactional datasets) to shed light on public health risks, such as COVID-19 (and underpin new forms of syndromic surveillance tools, providing capabilities for early-warning systems at scale; sustainably; and without reliance on self-reporting apps). 2. To uncover potentially hidden impacts of COVID-19 on vulnerable and under-examined communities (e.g. BAME, areas of Food Poverty, Deprivation) 3. To demonstrate the importance of transparency, security and privacy-by-design in data linkage systems, through open frameworks connecting key stakeholders: health services, researchers, private-sector data holders, and individuals/communities themselves. We expect the programme's work to directly impact on practices within our partners in the form of NHS, ONS, Joint Biosecurity Centre and Boots Pharmacy.
Date proposal received: 
Thursday, 11 March, 2021
Date proposal approved: 
Thursday, 11 March, 2021
Keywords: 
Epidemiology, Infection, Statistical methods, Linkage

B3731 - Feasibility assessment of RNA sequencing of blood spots - 22/03/2021

B number: 
B3731
Principal applicant name: 
Jennifer Silvers | University of California, Los Angeles
Co-applicants: 
Steve Cole
Title of project: 
Feasibility assessment of RNA sequencing of blood spots
Proposal summary: 

We are seeking to test the feasibility of doing RNA sequencing on blood spots as collected in the ALSPAC study. We have done this type of analysis on dry blood spots before but not on blood that was collected in a tube and then put on paper. We want to ensure the samples are viable for our planned analyses.

Impact of research: 
The feasibility analysis would inform whether the planned eventual research is possible. The planned future research would be the first to examine longitudinal changes in immune system markers across 3 timepoints in development. This could fundamentally shape our knowledge of neuroimmune functioning and launch a broader series of studies to examine how childhood experiences shape inflammatory disease.
Date proposal received: 
Thursday, 4 March, 2021
Date proposal approved: 
Monday, 8 March, 2021
Keywords: 
Immunology, RNA, Biological samples -e.g. blood, cell lines, saliva, etc., Development

B3732 - Association between social disadvantage and childrens language and literacy attainments between ages 3-and-9 - 08/03/2021

B number: 
B3732
Principal applicant name: 
Sonali Nag | University of Oxford (UK)
Co-applicants: 
Siyu Ma
Title of project: 
Association between social disadvantage and children’s language and literacy attainments between ages 3-and-9.
Proposal summary: 
Impact of research: 
We expect the work to inform the significant social predictors of the development of children’s language and literacy development. Understanding the impact of social disadvantage may benefit the development of screening tools for reading difficulties such as dyslexia, that can trace actual difficulties and rule out poor reading performance due to limited learning resources in deprived environments. We intend to present the findings at educational conferences and workshops, as well as scientific conferences and in peer-reviewed journals.
Date proposal received: 
Sunday, 7 March, 2021
Date proposal approved: 
Monday, 8 March, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Learning difficulty, Statistical methods, Childhood - childcare, childhood adversity

B3727 - Youth Vascular Consortium - 17/03/2021

B number: 
B3727
Principal applicant name: 
Chloe Park | University College London (United Kingdom)
Co-applicants: 
Dr Rachel Climie, Terence Fong
Title of project: 
Youth Vascular Consortium
Proposal summary: 

Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for nearly one-third of all deaths, and poses a major economic burden to the global healthcare system. Thus, the prevention of CVD is a public health priority and identifying individuals at increased cardiovascular risk at an early stage is of paramount importance for minimising disease progression.

Vascular ageing, the decline in vascular structure and function, is an integrated marker of overall cardiovascular risk burden on the vasculature over time and ultimately leads to end organ damage in the heart, brain and kidney. While age-dependent arterial damage typically appears in the fifth or sixth decade of life, there is wide variability between individuals with some displaying early vascular ageing. Exposure to environmental and genetic factors as early as during childhood or even during foetal life promotes the development and accumulation of subclinical vascular changes that directs an individual towards a trajectory of early vascular ageing. This has led to the concept that vascular age, as opposed to chronological age, may be better related to the prognosis of CVD.

However, research concerning vascular ageing in early life and/or adolescents is sparse despite substantial evidence indicating that the formative years of life play a significant role in contributing to traditional risk factors exhibited in adulthood. It is unclear what is normal vascular ageing in this population and no large-scale study has determined what specific factors contribute to accelerated vascular ageing in early life.

By creating the Vascular Youth Consortium we will be able to address these unkonwns. The findings of which, will be instrumental to clinicians in preventing the development of overt CVD later in life.

Impact of research: 
There are several expected outcomes from this consortium including: • The establishment of a collated databank containing study data from collaborators worldwide. • The establishment of reference values for vascular ageing in children, adolescents and young adults. • The identification of risk factors that contribute to early vascular ageing in the younger population. • The development of a predictive index of early vascular ageing in children, adolescents and young adults, based on identified risk factors. • A head-to-head comparison between different techniques used to determine vascular ageing in children, adolescents and young adults. The results of the consortium will be instrumental to clinicians in preventing the development of overt CVD later in life.
Date proposal received: 
Monday, 1 March, 2021
Date proposal approved: 
Friday, 5 March, 2021
Keywords: 
Physiology, Medical imaging, Ageing

B3730 - Exposure to green and blue spaces and working memory in children aged 5-12 - 04/03/2021

B number: 
B3730
Principal applicant name: 
Mikel Subiza Pérez | University of the Basque Country UPV/EHU (Spain)
Co-applicants: 
Dr. Aitana Lertxundi, Gonzalo García-Baquero
Title of project: 
Exposure to green and blue spaces and working memory in children aged 5-12
Proposal summary: 

Current scientific evidence suggests that exposure to green and blue spaces and infraestructures (e.g. parks, rivers, street trees...) may have an impact on human's health and that this effect might be partiallt explained by the sequestration of air pollutants. The general aim of the project is to analyze the association of various residential green and blue space metrics with working memory in children aged 5-12 years old in European birth cohorts.

Impact of research: 
We think our contribution will be relevant due to the large sample of participants available for the analyses and the use of a relatively novel variable in the greenness-cognition literature as most of the previous studies have focused on attention, IQ or academic performance. Besides, the inclusion of metrics of exposure to blue spaces will also mean a relevant step forward. In all, we will generate more evidence on environmental health that could inspire future policies and interventions.
Date proposal received: 
Thursday, 4 March, 2021
Date proposal approved: 
Thursday, 4 March, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Cognitive impairment, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Environment - enviromental exposure, pollution

B3726 - DNA methylation score development for in utero exposure to paternal smoking - 01/03/2021

B number: 
B3726
Principal applicant name: 
Diana Ivankovic | Clemson University (USA)
Co-applicants: 
Cristy Stagnar
Title of project: 
DNA methylation score development for in utero exposure to paternal smoking
Proposal summary: 

The ability of environmental conditions to influence phenotypes in future generations requires that environmental exposures induce changes in the epigenome of male gametes via the transmission of aberrant sperm epigenetic marks following fertilization. Studies have demonstrated that exposure to cannabis and tobacco products alter sperm DNA methylation. Thus, it is important to investigate environmental exposures, including cigarettes and cannabis, and their effect on the male gametes during the crucial pre and periconception window. In addition, there is a need to determine whether these methylation marks are heritable and associated with health outcomes in the progeny, especially given that men are the predominant cannabis and tobacco product consumers, and their use is increasing. Our machine learning-based DNA methylation score is based on cord blood measurements of DNA methylation (Illumina’s Infinium HumanMethylation450K BeadChip) and will reflect exposure to paternal smoking pre and during pregnancy.

Impact of research: 
A machine learning-based DNA methylation score will be useful in studies of childhood health outcomes to fill in the inevitable missing data on whether or for how long a father smoked and to validate self-reports of nonsmoking. It will also enable its implementation in adjusting epigenome-wide DNA methylation association studies for this early-life exposure.
Date proposal received: 
Sunday, 28 February, 2021
Date proposal approved: 
Monday, 1 March, 2021
Keywords: 
Bioinformatics, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, Statistical methods

B3725 - Exercise and Mental Health in Children with Neurodevelopmental Conditions - 04/03/2021

B number: 
B3725
Principal applicant name: 
Umar Toseeb | University of York
Co-applicants: 
Title of project: 
Exercise and Mental Health in Children with Neurodevelopmental Conditions
Proposal summary: 
Impact of research: 
This unique project will help to elucidate the mechanisms via which exercise and mental health are related in children with neurodevelopmental conditions. Parents of children with neurodevelopmental conditions will be consulted during the initial stages of study development and during the dissemination of the findings. By understanding how exercise and mental health are related in children with neurodevelopmental conditions we hope to be in a position to inform the development of educational programmes and parenting strategies designed to optimise exercise in ways that are bespoke to specific challenges. Findings will be shared with policy makers and practitioners through targeted policy briefs, a workshop, and press releases news articles aimed at the general public.
Date proposal received: 
Friday, 26 February, 2021
Date proposal approved: 
Monday, 1 March, 2021
Keywords: 
Social Science, Developmental disorders - autism, Learning difficulty, Mental health, Speech/language problem, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Genomics, Physical - activity, fitness, function, Speech and language, Statistical methods

B3723 - Nature vs nurture of type 2 diabetes applying polygenic risk scores to dissect genetic from environmental effects on type 2 dia - 01/03/2021

B number: 
B3723
Principal applicant name: 
Despoina Manousaki | University of Montreal (Canada)
Co-applicants: 
Melanie Henderson, Nicholas J Timpson, Laura Corbin, Faegheh Ghanbari Divshali, Nahid Yazdan Panah
Title of project: 
Nature vs nurture of type 2 diabetes: applying polygenic risk scores to dissect genetic from environmental effects on type 2 dia
Proposal summary: 

Type 2 diabetes (T2D) is a heritable disease leading to an abnormal glucose metabolism, influenced by multiple genetic variants across the genome. Although common in adults, T2D was previously rare in childhood, but its prevalence in this age group has been increasing in the past two decades as a result of the childhood obesity pandemic, accounting for up to 45% of cases of diabetes in youth in certain at-risk populations. The prevalence of prediabetes (an early stage of T2D, which is characterized by elevated blood sugar below the threshold to diagnose T2D) is even higher among obese children. Furthermore, individuals who develop both prediabetes and T2D in childhood and adolescence develop early microvascular complications, whose treatment failure is high. Thus, prevention of young-onset T2D using targeted lifestyle modification presents a particularly important yet difficult challenge. As such, identifying children at increased risk early in their lives is critical for these targeted interventions. Additionally, quantifying the genetic liability to youth-onset T2D could help better understand the respective contributions of environment vs genetics in the etiology of this disease. For instance, it is crucial to understand if among children with increased genetic risk for T2D, a favorable environment can prevent the development of T2D.
T2D has a polygenic nature, with an important heritable component explaining between 20% and 80% of the risk to develop this disease. Polygenic risk scores (PRS) have been demonstrated to have an improving ability to identify adult individuals at significantly high/low predisposition towards polygenic diseases. Therefore, it has become possible to identify adults who will lie at the extreme distribution of a trait, such as risk of T2D. T2D is causally linked to obesity. Obesity, as expressed by the measures of body mass index (BMI), is also a highly heritable polygenic trait. A PRS for adult BMI (Khera et al, Cell 2019) has been able to predict differences in body weight in ALSPAC children as early as at birth, with increasing predictive performance as individuals grow older.
Therefore, we posit that, similar to the PRS for BMI, a PRS for adult T2D, in combination with clinical risk factors (such as nutrition and physical activity) may be able to effectively predict individuals presenting abnormal glycemic traits in childhood. Since T2D and prediabetes in both adults and children is causally linked to obesity, we will also test if a PRS for adult BMI predicts abnormal glycemic traits in children. We will then compare the predictive performance of the PRSes and combine them with traditional non-genetic risk factors to enhance T2D risk prediction in youth. Finally, among children at the extremities of the PRS distribution (ie children with the highest and lowest genetic risk for T2D), we will seek to identify which environmental factors mitigate the effects of this genetic risk, and either contribute or prevent the development of T2D. To do this, we will use a large pediatric cohort representing the general population (ALSPAC), as well as a population of children at risk of obesity (QUALITY), both of predominantly European ancestry.

Impact of research: 
Our study can potentially stratify for risk of T2D among children, based on PRS derivable at no risk and low cost. Such a stratification is likely to improve screening for candidates for targeted lifestyle interventions, while optimizing allocation of medical resources. Individuals who maintain normal glycemic profile despite an unfavorable PRS – or develop T2D despite a favorable PRS – may be of particular interest, since the discordance between polygenic susceptibility and clinical phenotype in these individuals could result from a disproportionate influence of environment. As such, this study can lead to interesting conclusions on the “nature vs nurture” of T2D in youth. Finally, a clear understanding of the genetic predisposition to obesity may help to destigmatize obesity among patients, their health care providers, and the general public.
Date proposal received: 
Monday, 22 February, 2021
Date proposal approved: 
Tuesday, 23 February, 2021
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, GWAS, Genetic epidemiology

B3722 - Associations of Cardiorespiratory Fitness Body Composition Physical Activity and Sedentary Time with Cardiometabolic risks - 03/05/2021

B number: 
B3722
Principal applicant name: 
Andrew O. Agbaje | University of Eastern Finland (Finland)
Co-applicants: 
Samuel Barmi, RN, MPH, Prof. Alan R. Barker, Prof. Tomi-Pekka Tuomainen
Title of project: 
Associations of Cardiorespiratory Fitness, Body Composition, Physical Activity and Sedentary Time with Cardiometabolic risks
Proposal summary: 

Components of physical fitness such as physical activity and body composition has been associated with cardiometabolic risk factors in children and adolescents in several cross-sectional and a few longitudinal studies. However, it remains unclear how objectively measured cardiorespiratory fitness, physical activity, and sedentary time and body composition associates with individual and clustered cardiometabolic risk factors from childhood (9 years) through young adulthood (24.5 years). Our current projects B3455 and B3622 are investigating the roles of these predictors with vascular outcomes from childhood through young adulthood. For a holistic understanding of the interrelatedness of vascular and cardiometabolic health across early life, we are therefore investigating this further using our current ALPSAC project data.

Impact of research: 
Our research has the potential to improve understanding of the physiological mechanism and epidemiology of disease evolution.
Date proposal received: 
Monday, 22 February, 2021
Date proposal approved: 
Monday, 22 February, 2021
Keywords: 
Epidemiology, Diabetes, Hypertension, Obesity, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Blood pressure, BMI, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Physical - activity, fitness, function, Puberty, Sex differences, Statistical methods

B3720 - NCS Cohort Project ARQ3 COVID-19 and Healthcare Disruption - 18/02/2021

B number: 
B3720
Principal applicant name: 
Alex Kwong | IEU / PHS
Co-applicants: 
Professor Nic Timpson, Dr Kate Northstone
Title of project: 
NCS Cohort Project ARQ3 COVID-19 and Healthcare Disruption
Proposal summary: 

The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society. To reduce the spread of the infection, the UK government imposed strong restrictive measures across England, Scotland, and Wales, including the lockdown announced on 23rd March 2020, as well as strict physical distancing rules. These infection control measures, as well as the diversion of resources towards COVID-19 services has resulted in substantial disruption to UK health care and delivery.

Recent reports from NHS digital indicate a 153-fold increase in those waiting 12 months or more for elective treatments, compared to 2020.1 Furthermore, despite a decrease in those attending A&E services, the number of patients waiting over 12 hours for admission was 34% higher in January 2021 than January 2020. Furthermore, disruption to pharmacological treatments has also been reported with delays to accessing medication.

Although restrictive measures were implemented universally to the UK population, it has become apparent that not all those are affected equally, with some individuals impacted more than others.

As a result of the health inequalities, which have been well documented for decades, exist based on sex, ethnicity and socioeconomic status, there is an increased concern that these groups will be disproportionately impacted in terms of healthcare disruption.

The aim of this project is to investigate sociodemographic predictors of healthcare disruption during the COVID-19 pandemic.

Impact of research: 
Policy change
Date proposal received: 
Wednesday, 17 February, 2021
Date proposal approved: 
Thursday, 18 February, 2021
Keywords: 
Health Services Research/Health Systems Research

B3719 - Maternal asthma and offspring methylation EWAS Meta-analysis of PACE cohorts - 16/02/2021

B number: 
B3719
Principal applicant name: 
Raquel Granell | University of Bristol
Co-applicants: 
Klaus Bønnelykke, Professor, Hanna Elliott, Dr
Title of project: 
Maternal asthma and offspring methylation: EWAS Meta-analysis of PACE cohorts
Proposal summary: 

Background
Asthma is a highly heritable disease with parental asthma being the strongest known risk factor for asthma in the offspring. Maternal asthma is a stronger risk factor than paternal asthma suggesting a role of epigenetic effects. Furthermore, clinical studies have suggested that parental effects might be sex-specific.

Impact of research: 
Date proposal received: 
Monday, 15 February, 2021
Date proposal approved: 
Tuesday, 16 February, 2021
Keywords: 
Genetics, EWAS, Epigenetics

B3716 - Ultra-processed food and DNA methylation age acceleration - 15/02/2021

B number: 
B3716
Principal applicant name: 
Oliver Robinson | IMPERIAL COLLEGE LONDON (United Kingdom)
Co-applicants: 
Adam Koczoski
Title of project: 
Ultra-processed food and DNA methylation age acceleration
Proposal summary: 

This project will analyse data already transferred under project: B3258 STOP: Science and Technology in childhood
Obesity Policy

Ultra-processed food (UPF) has become increasingly common in the diets of children, particularly in the UK. Consumption of UPF has been linked with obesity, cardio-metabolic disease and some cancers, independently of total energy intake and nutritional composition. Mechanisms through which UPF effects health remain unclear. DNA methylation can be used to compute a measure of biological age using methods developed by Horvath and others. Age acceleration (AA, having a higher DNA methylation age than chronological age) measured in children may reflect developmental processes and epigenetic stability and is strongly related to child obesity. We propose to explore the effects of UPF on AA in ALSPAC children and its role in the development of obesity

Impact of research: 
May add to understanding of mechanism of effects of UFP on child development. Student will gain knowledge of analytical methods
Date proposal received: 
Wednesday, 10 February, 2021
Date proposal approved: 
Monday, 15 February, 2021
Keywords: 
Epidemiology, Obesity, DNA sequencing, Statistical methods, BMI, Development, Epigenetics, Nutrition - breast feeding, diet

B3718 - Relationships between stress ageing and risk-taking behaviour - 15/02/2021

B number: 
B3718
Principal applicant name: 
Tim Fawcett | University of Exeter (UK)
Co-applicants: 
Stephanie Hunt, Dr Doretta Caramaschi, Dr Caroline Wright
Title of project: 
Relationships between stress, ageing and risk-taking behaviour
Proposal summary: 

The propensity to take risks is highly variable between individuals. Individuals who suffer stressful experiences early in life tend to show faster physiological development, an effect known as ‘psychosocial age acceleration’. Evolutionary theories predict that individuals who experience accelerated ageing are more likely to become risk-takers, as their likelihood of morbidity and mortality later in life is increased, and they therefore have less to lose and more to gain by taking risks. This predicts a ‘pace-of-life’ syndrome in which individuals exposed to early stress adopt a “live fast, die young” attitude, whereas those under less stress are more risk averse (Ellis et al. 2009; DOI: 10.1007/s12110-009-9063-7). Alternatively, the causality could be reversed – increased risk-taking could increase stress, and thereby accelerate ageing. As of yet, there are hardly any tests of these predictions in humans, and none that investigate causality. In this project, we will test whether groups of people who have inherited different genetic variants for epigenetic age acceleration differ in their risk-taking behaviour; or, conversely, whether those who have inherited different genetic variants for risk-taking behaviour differ in epigenetic markers of ageing.

Impact of research: 
This project will be the first to investigate the causal relationship between biological aging and risk-taking behaviours. In doing this, insights from this project will contribute to our understanding of the biological basis of human risky behaviours.
Date proposal received: 
Thursday, 11 February, 2021
Date proposal approved: 
Monday, 15 February, 2021
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Childhood - childcare, childhood adversity, Epigenetics, Genetic epidemiology, Mendelian randomisation, Social science

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