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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B3619 - Depositing data with DPUK a trial dataset - 22/09/2020

B number: 
B3619
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Dr Sarah Bauermeister
Title of project: 
Depositing data with DPUK: a trial dataset
Proposal summary: 

As part of our commitment to DPUK (https://www.dementiasplatform.uk/) we are developing a trial dataset to be classified using the DPUK ontology and for the variable list to be uploaded to the DPUK data portal. Further developments may take place if hte trial proves successful.

Impact of research: 
Date proposal received: 
Friday, 18 September, 2020
Date proposal approved: 
Tuesday, 22 September, 2020
Keywords: 
Neurology, Cognitive impairment, Cognition - cognitive function

B3616 - Implications of covid-19 lockdown for inequalities in health student mini project - 22/09/2020

B number: 
B3616
Principal applicant name: 
Laura Howe | IEU (United Kingdom)
Co-applicants: 
Madeleine Smith, Amanda Hughes
Title of project: 
Implications of covid-19 lockdown for inequalities in health student mini project
Proposal summary: 

Stark inequalities in health already exist in the UK, with people from lower socioeconomic backgrounds suffering from greater levels of ill health across multiple domains. The covid-19 pandemic potentially threatens to worsen these health inequalities. The ‘lockdown’ changed people’s behaviour radically, but the socioeconomic differences in these experiences are not well understood. Some groups of society may have increased health-promoting behaviours – for example, engaging in more physical activity and preparing more food within the home. Other groups may have experienced adverse changes in health-related behaviours – for example, smoking more or consuming more alcohol in response to the stress and anxiety induced by the pandemic. It is possible these differences are socioeconomically patterned, and could therefore worsen pre-existing inequalities. Another key factor likely to influence patterns of behaviour change during the pandemic is household/family structure. For example, parents with children and individuals shielding or living with a household member who was shielding may have been less able to engage with health-promoting behaviours.

Data from the Office for National Statistics demonstrate that between 23rd March and 5th April 2020, 27% of the UK workforce were furloughed due to the COVID-19 lockdown. Many others lost jobs, or had working hours and income reduced. The adverse financial and employment consequences of the covid-19 lockdown are concentrated in already vulnerable groups of society – they are more likely to be experienced by people in insecure or low-paid jobs. The young adults in ALSPAC are in the age groups most likely to have been affected by furlough, job losses, and loss of pay or hours (https://www.resolutionfoundation.org/publications/young-workers-in-the-c...). Detailed pre-pandemic data from the ALSPAC cohort offers the opportunity to better understand which groups of society were more likely to be impacted financially by the lockdown. We will explore whether SEP, adverse childhood experiences, pre-existing mental health problems, obesity, smoking, alcohol use, shielding or living with a household member who was shielding, and family structure are associated with greater likelihood of adverse financial changes during covid-19, and hence whether the lockdown is likely to exacerbate health challenges for these groups.

Impact of research: 
understanding of inequalities in relation to covid-19 lockdown
Date proposal received: 
Wednesday, 16 September, 2020
Date proposal approved: 
Tuesday, 22 September, 2020
Keywords: 
Epidemiology

B3615 - Research-on-research Blinded data analysis to improve the robustness and reproducibility of health research - 08/10/2020

B number: 
B3615
Principal applicant name: 
Robert Thibault | University of Bristol (United Kingdom)
Co-applicants: 
Prof Marcus Munafo
Title of project: 
Research-on-research: Blinded data analysis to improve the robustness and reproducibility of health research
Proposal summary: 

Bias in scientific research can lead to research waste and useless or even harmful health care and policy interventions. To reduce bias, researchers commonly employ experimental designs that blind both participants and outcome assessors. Data analysts, however, are rarely blinded. Here, we propose to test whether blinding data analysts improves the reliability of published research findings. To execute the study, we will randomize researchers who request the Avon Longitudinal Study of Parents and Children (ALSPAC) dataset, and consent to partake in the research, to receive either data from only 10% of participants, or data from all participants. Researchers who receive 10% of the data will develop their analysis based on this subset and be asked to register their analysis plan. After registering their analysis plan, the full dataset will be provided. We call this “Blind Access”. Researchers who receive the full dataset will not be required to register their analysis. We call this “Standard Access”. We will then compare the reliability of the published findings between the Blind Access and Standard Access groups.

Impact of research: 
1. If we find that blinded data analyses are less biased than non-blinded analyses, this will be the first substantial empirical evidence to support blinded data analysis in health research. This finding would promote researchers to conduct blinded data analyses and in turn increase the robustness and reproducibility of published research findings. 2. We will garner information on how best to implement blinded data analysis. This will be useful information for data managers, including ALSPAC. 3. If we find that blinded data analyses and non-blinded data analyses are similarly biased, then we will have documented that this initiative is not necessarily worth pursuing.
Date proposal received: 
Saturday, 12 September, 2020
Date proposal approved: 
Tuesday, 15 September, 2020
Keywords: 
Statistics/methodology, This project is not concerned with a disease or condition. We are conducting 'research on research' to improve the robustness and reproducibility across observational health research., Statistical methods, meta-research blind data analysis

B3613 - Deep phenotyping of cardiovascular systems physiology in adults born to hypertensive pregnancies - 10/09/2020

B number: 
B3613
Principal applicant name: 
Adam Lewandowski | University of Oxford (RDM Cardiovascular Medicine) (United Kingdom)
Co-applicants: 
Title of project: 
Deep phenotyping of cardiovascular systems physiology in adults born to hypertensive pregnancies
Proposal summary: 

New-onset hypertension during pregnancy occurs in up to 10% of women. People born to pregnancies complicated by hypertension (i.e. gestational hypertension and preeclampsia) are at increased risk for cardiovascular disorders, including hypertension and stroke, in later life. The underlying disease process is identifiable in the first decades of life with evidence of emerging damage to their hearts and blood vessels. Phenotypic changes that have been observed in early postnatal life and as they reach young adulthood include higher blood pressure, altered heart structure and function, as well as a reduced number, size, and function of small blood vessels. However, to date, longitudinal data in the same individuals, as well as a multi-systems, deep phenotyping approach to characterizing cardiovascular physiology in offspring of hypertensive pregnancies, remains limited. By using ALSPAC, we will be able to make use of the previously collected demographic, anthropometric, and phenotypic data collected. We will also design a new study in 200 young adults, of which 100 will be born to hypertensive pregnancies and 100 born to normotensive pregnancies. These participants will be invited by the ALSPAC team to travel to Oxford for a 3 hour study visit, including blood sample collection, exercise stress testing, blood pressure and imaging of the small blood vessels in the eye, brain MRI, as well heart scans using both MRI and echocardiography at rest and during exercise. By studying and tracking changes both temporally and spatially across multiple organs, we will be able to better describe and quantify the multi-dimensional landscape of hypertensive disease progression.

Impact of research: 
Our ultimate goal is to be able to better characterise temporal trends in disease progression in people born to hypertensive pregnancy, and to then translate this to the development of clinical tools, for application at scale.
Date proposal received: 
Tuesday, 8 September, 2020
Date proposal approved: 
Wednesday, 9 September, 2020
Keywords: 
Clinical research/clinical practice, Hypertension, Medical imaging, Birth outcomes

B3612 - Using detailed cohort data to investigate collider bias in mental health outcomes - 08/09/2020

B number: 
B3612
Principal applicant name: 
Gareth Griffith | University of Bristol MRC-IEU (United Kingdom)
Co-applicants: 
Dan Smith, Matt Tudball, Dr Tim Morris, Dr Hannah Sallis, Professor Kate Tilling, Professor George Davey Smith, Professor Marcus Munafo
Title of project: 
Using detailed cohort data to investigate collider bias in mental health outcomes.
Proposal summary: 

The need for comprehensive and representative data collection on populations for epidemiological research has been brought into sharp focus by the COVID-19 pandemic. This has resulted in the generation of many COVID-specific modules within existing cohorts and datasets (e.g. Henderson et al, 2020, Kwong et al, 2020). These datasets are going to be invaluable in understanding the mental health response of individuals to the COVID-19 pandemic. These studies reflect individuals responding under unique circumstances, presenting unique selection effects, which have the capacity to substantially bias results (Griffith et al. 2020). These selection effects are likely to be particularly stark with respect to mental health, which is known to be associated with non-response (Kwong, 2019). The data and analysis will be carried out by GG and DS, and data stored on the University of Bristol RDSF.

Impact of research: 
Elucidate potential impacts of non-random dropout, selection and collider bias. Increase understanding of the importance of representation in a mental health context.
Date proposal received: 
Monday, 7 September, 2020
Date proposal approved: 
Tuesday, 8 September, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3608 - Do poverty-reduction fiscal policies reduce childhood obesity A study based on microsimulations and scenario evaluations - 29/09/2020

B number: 
B3608
Principal applicant name: 
Costanza Pizzi | University of Turin
Co-applicants: 
Davide Rasella
Title of project: 
Do poverty-reduction fiscal policies reduce childhood obesity? A study based on microsimulations and scenario evaluations.
Proposal summary: 
Impact of research: 
Date proposal received: 
Monday, 31 August, 2020
Date proposal approved: 
Tuesday, 8 September, 2020
Keywords: 
Health Economics

B3610 - Understanding the relationship between autism and personality disorder an epidemiological study - 04/09/2020

B number: 
B3610
Principal applicant name: 
Paul Moran | University of Bristol (United Kingdom)
Co-applicants: 
Dheeraj Rai, Rebecca Pearson, Sarah Douglas
Title of project: 
Understanding the relationship between autism and personality disorder: an epidemiological study
Proposal summary: 

People with autism and those with personality disorder often experience difficulties in understanding and responding to their emotions and managing relationships with others. The overlapping nature of these symptoms means that health professionals sometimes find it difficult to distinguish the presence of autism from personality disorder in an individual. To date, very little research has examined the diagnostic overlap between autism and personality disorder and the potential links, as well as the differences between these two conditions, are not well understood. For example, it is unclear whether any features of autism are associated with the future development of personality disorder.

We propose to undertake the first robust scientific study of these issues, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a world leading cohort study. We will accelerate knowledge in the field by clearly establishing whether a link exists between autism and personality disorder. We will explore a wide range of biological, psychological and social factors that might be driving the association, ranging from genes through to the experience of being bullied as a child. Our study has the potential to make a difference to the lives of people with personality disorder and autism. This is because the knowledge that we will develop about the potential pathways between autism and personality disorder will improve the support and care offered to people with these conditions in the future.

Impact of research: 
Beyond understanding the relative risk of personality disorder in individuals with autism, it is also important to understand the nature of any risk or protective factors on a pathway from autistic traits to later personality disorder/personality difficulties. This is because such information could help to inform the development of more effective interventions that will benefit service users and their families.
Date proposal received: 
Wednesday, 2 September, 2020
Date proposal approved: 
Friday, 4 September, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3600 - Investigating the effects of autism related exposures on BMI and disordered eating behaviours in adulthood - 02/09/2020

B number: 
B3600
Principal applicant name: 
Dheeraj Rai | Bristol Medical School, Centre of Academic Mental Health, Centre for Academic Primary Care (United Kingdom)
Co-applicants: 
Ms Amanda Ly, Dr. Evangelia Stergiakouli, Dr. Jon Heron
Title of project: 
Investigating the effects of autism related exposures on BMI and disordered eating behaviours in adulthood.
Proposal summary: 

Autism is a lifelong condition characterised by difficulties with social interaction, social communication and repetitive behaviours. In recent decades, the number of children and adults diagnosed with autism has increased. As autism is heritable, genetic risk may explain why there are some individuals with mild autistic traits but they may not meet the criteria for an autism diagnosis and subsequent treatment or other support requirements. As more children with autism and mild autistic traits reach adulthood, the need for support from health and other services will likely increase. However, few large, population based longitudinal studies involving adults with autism/autistic traits exist, representing a research gap.

During this phase of my PhD project, I will study how autism and autism traits, including genetic risk for autism, may be associated with BMI and disordered eating behaviours in adulthood. Children with autism often having sensory issues and unusual eating preferences, which could have an effect on growth and health in adult life. It has been reported that social communication difficulties may increase the risk of disordered eating patterns in adolescence. This implies that maintaining a healthy BMI may be challenging during this period and that there is a possible increased risk of disordered eating behaviours and eating disorders in adulthood for those with social communication difficulties. This phase of my PhD project is focussed on whether autistic individuals are more likely to have high BMI and disordered eating behaviours in adulthood. Changes in growth during late childhood into late adolescence will also be studied to assess whether there are critical periods that are suitable for intervention.

Impact of research: 
Understanding of the relationship between autism or core features of autism, BMI and disordered eating in adulthood. Possible identification of risk periods suitable for intervention.
Date proposal received: 
Wednesday, 26 August, 2020
Date proposal approved: 
Wednesday, 2 September, 2020
Keywords: 
Epidemiology, Developmental disorders - autism, Eating disorders - anorexia, bulimia, Obesity, Statistical methods, BMI, Development, Genetic epidemiology

B3607 - The relationship between sedentary time sedentary patterns and cognitive functions in adolescents and young adults - 02/09/2020

B number: 
B3607
Principal applicant name: 
Dominika M Pindus | University of Illinois at Urbana-Champaign (US)
Co-applicants: 
Ms Ana Laura Selzer Ninomiya
Title of project: 
The relationship between sedentary time, sedentary patterns and cognitive functions in adolescents and young adults
Proposal summary: 

Previous research has shown that time spent viewing TV or in self-reported sedentary behaviors is related to suboptimal cognitive functioning in older adults. However, not all sedentary behaviors show negative relationship with cognitive functions and most studies focused on leisure time sedentary behaviors. Consequently, these studies were unable to assess the relationship between daily volume of sedentary time and cognitive functions. Physiological adaptations to sedentary lifestyle include adverse cardio-metabolic profiles and low-grade inflammation. These physiological responses contribute to suboptimal brain and cognitive functions. Chronic stress has been negatively related to cognitive functions in youth and adults. Socio-economic status is one of the correlates of sedentary behaviors and higher levels of chronic stress have been observed among individuals with low socio-economic status. Thus, individual differences in chronic stress may help explain the associations between sedentary time, physical inactivity and suboptimal cognitive functioning. Furthermore, it is important to ascertain which biological pathways may be specific to excessive engagement in sedentary time. Adolescence and young adulthood are the most opportune periods to study these relationships due to low prevalence of chronic disease and comorbid conditions compared to middle-aged and older adults, high levels of sedentary time (adolescents are the most sedentary group after older adults, and European adolescents spend on average 7.5 hours per day sedentary) and protracted development of higher order cognitive functions yielding them amenable to behavioral interventions during these developmental periods.

Impact of research: 
Our work will help elucidate the role of potential biological pathways that may help explain the relationship between objectively measured sedentary time, physical activity and cognitive functions in adolescents and young adults from ALSPAC.
Date proposal received: 
Saturday, 29 August, 2020
Date proposal approved: 
Wednesday, 2 September, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Obesity, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cognition - cognitive function, Physical - activity, fitness, function

B3605 - Genetic influences on infant and childhood growth - 02/09/2020

B number: 
B3605
Principal applicant name: 
Stefan johansson | Department of clinical science, university of Bergen, Bergen, Norway (Norway)
Co-applicants: 
Øyvind Helgeland, Pål R Njølstad, Marc Vaudel
Title of project: 
Genetic influences on infant and childhood growth
Proposal summary: 

The obesity epidemic is one of the most important health challenges of the 21st century.
Identifying genetic factors predisposing to weight gain is crucial for identifying biological processes important for weight-control and help identify individuals already at young age that might benefit from health interventions and thereby reducing their risk for disorders such as type 2 diabetes that follow in its footpath.

While there is great progress deciphering the genetic factors influencing weight in in adulthood, and at birth, there is a huge knowledge gap on the role of the genomes of the child and its parents in infancy and childhood into puberty. This is very unfortunate, as it is firmly established that the BMI-development during the first 6 years of life are strong predictors of obesity in adolescence . Results from our own ongoing work in the Norwegian Mother, Father and Child and work of others show that it is possible to find novel genetic variants with specific and substantial effect on weight development during infancy with high quality data and large GWAS sample sizes.

Impact of research: 
We believe our data will provide much better understanding of the genetic and molecular insight toward healthy and unhealthy weight trajectories.
Date proposal received: 
Saturday, 22 August, 2020
Date proposal approved: 
Wednesday, 2 September, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, DNA sequencing, GWAS, Statistical methods, Endocrine - endocrine disrupters, Fathers, Offspring, Whole genome sequencing, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Hormones - cortisol, IGF, thyroid, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet

B3317 - Visual Impairment in Psychosis Cause Consequence or Biomarker - 25/08/2020

B number: 
B3317
Principal applicant name: 
Claudia Cooper | University College London (United Kingdom)
Co-applicants: 
Claudia Cooper, Joseph Hayes, Karoline Kuchenbaecker, Gemma Lewis, Natalie Shoham
Title of project: 
Visual Impairment in Psychosis: Cause, Consequence, or Biomarker?
Proposal summary: 

Eyesight Problems and Psychotic Illnesses: What’s the Link?
Psychotic illnesses affect just under 1% of people in England. Symptoms include hearing voices and experiencing confusing and distressing thoughts. These often begin in early adulthood, and can have a major effect on people’s lives.
People with psychotic illnesses seem to have more eyesight problems. We are not sure why, but it might be because:
• Possibility 1: Some people with psychotic illnesses find it harder to look after their health including their eyes, for example by going to the optician’s.
• Possibility 2: The same brain changes cause eyesight problems and psychotic illnesses.
• Possibility 3: Eyesight problems increase a person’s chances of having a psychotic illnesses.
I plan to look at which of these best explains the link between eyesight problems and psychosis. If people with psychosis have less eye care (possibility 1), we need to improve this. If possibility 2 is correct, eye research might hold the key to understanding more about the brain changes that cause psychosis. Or, if eyesight problems lead to psychosis, then improving eye health could be a way of preventing or reducing psychosis.
I will start by reviewing past research, to make sure I base my work on the most up-to-date information. I will then carry out research using two large datasets: UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC).
UK Biobank has information on over half a million 40 to 69-year-olds including questionnaires, eyesight tests and genetic tests.
ALSPAC has information on 14,500 UK families. The children have been followed up since before birth and will be 25.
I will look at UK Biobank and ALSPAC because older and younger people are most at risk of developing psychosis. In these datasets, I will see if people with short-sight genes have more psychotic illnesses. If so, this would be evidence that poor eyesight can lead to psychosis. Genes are present before birth, so I will know that they came before any psychotic illness began. I will also find out if genes for psychotic illnesses are linked with eyesight problems. This would suggest the reverse: that psychosis leads to poor eyesight.
I will also use a third, Israeli dataset. All Israeli 17-year-olds have health checks to decide if they can join the armed forces. I will use this data to find out if teenagers with eyesight problems are more likely to have a psychotic illness over the following years. If so, I will see what level of eyesight problems are associated with developing psychosis. This will allow me to test the theory that perfect eyesight and complete blindness both protect against psychosis, with moderate eyesight problems carrying the highest risk.
Throughout this research, I will chair a group every 6 months. It will include people with psychosis, people with eyesight problems, carers, charity members and doctors. We will discuss study findings and think about how to use them to improve the experiences of people with eyesight problems and psychosis. This will include plans to publicise findings, influence healthcare and plan new studies.
When the research is finished, I will tell healthcare professionals and researchers about the results at meetings and in journals. I will also write about them in publications read by people with mental health and eyesight problems. I will offer to present findings to public groups, through links with the Royal National Institute for the Blind (RNIB) and a forum of mental health service users.
People with eyesight problems and mental health service users helped to write this summary.

Impact of research: 
I will aim to publish findings in peer-reviewed journals. An implementation group will meet six-monthly, with particular emphasis on pathways to impact. They will advise on opportunities to disseminate findings via healthcare professionals, charities, and patient and carer groups, and develop plans to influence clinical practice, for example by responding to NICE and other relevant consultations. Visual impairment can be debilitating and is preventable in around 50% of cases. If we demonstrate evidence that psychosis increase risk of visual impairment (hypothesis 1), this would represent a major unmet need in people with psychosis; a health inequality that could and ought to be addressed. This may be different between younger people, who are most likely to experience a first episode of ‘non-organic’ psychosis associated with neurodevelopment, and older people, who are at higher risk of having psychotic symptoms associated with neurodegeneration. Older people are also more likely to have non-myopia causes of visual impairment than younger people. Studying the ophthalmic changes that lead to visual deterioration in psychosis could provide insights into the neurological processes underlying some psychotic illnesses, potentially informing the development of new treatments. It has been proposed, based on this hypothesis, that retinal nerve fibre layer thickness could be used as a diagnostic test for schizophrenia. If we demonstrate evidence supporting hypothesis 3, offering eye tests to people at high risk of or in the early stages of a psychotic illness could be a rational intervention to test. Training in visual processing has also been suggested as a possible therapeutic intervention for people with psychotic illnesses and visual impairment based on the hypothesis that visual impairment may contribute to its development.
Date proposal received: 
Wednesday, 12 August, 2020
Date proposal approved: 
Tuesday, 25 August, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health

B3604 - Positive and adverse childhood experiences and cardiovascular disease risk - 25/08/2020

B number: 
B3604
Principal applicant name: 
Rebecca Lacey | UCL (UK)
Co-applicants: 
Dr Naomi Priest
Title of project: 
Positive and adverse childhood experiences and cardiovascular disease risk
Proposal summary: 

Cardiovascular diseases (CVDs) are a significant public health concern and are a leading cause of mortality, representing 31% of all global deaths in 2017. These diseases often have their origins in childhood. Ample evidence suggests that exposure to childhood adversity, such as experiences of violence, parent imprisonment, household mental illness or substance use, has harmful effects on cardiovascular and other non-communicable diseases. Experiencing two or more adversities is associated with higher risk of cardiovascular disease in Europe and North America, respectively, corresponding to US$150 and US$164 billion in associated costs. Whilst there is evidence that adverse childhood experiences are associated with higher cardiovascular risk, whether socioeconomic inequalities in cardiovascular risk might be explained by childhood adversities. Understanding the extent to which adverse experiences in childhood could potentially explain socioeconomic inequities in CVD risk would help to inform the targeting of resources.

Further, the milieu of the family environment includes not just adverse experiences, however, but also positive experiences, which have been understudied. Positive experiences do not simply reflect the absence of risk factors, but instead are independent attributes or assets that enhance health and resilience over time. For example, the absence of abuse in the household does not necessary imply optimal parenting. The Health Outcomes from Positive Experiences (HOPE) is a complimentary framework to childhood adversity that organises positive childhood experiences into four broad categories: Being in nurturing, supportive relationships; Living, developing, playing, and learning in safe, stable, protective, and equitable environments; Having opportunities for constructive social engagement and to develop a sense of connectedness; and Learning social and emotional competencies.

Emerging evidence suggests that positive childhood experiences – variably defined – are associated with better adult cardiovascular health. These studies are suggestive that positive experiences in childhood also have relevance for cardiovascular health. To fully understand children’s experiences in the early years and how environments can be optimised to promote cardiovascular health in later life, however, we need to capture both adverse and positive experiences in childhood; otherwise, we just look at half the picture. For example, no previous studies have examined whether the effect of positive experiences was evident over and above that of adverse experiences in childhood. While adverse and positive experiences are not the inverse of one another, they are negatively correlated. Do positive experiences actually matter for cardiovascular health, or are they just a proxy indicator for the absence of adverse experiences? If they do matter, can they help to promote resilience in the presence of childhood adversity; that is, good health despite the presence of adversity?

Impact of research: 
Findings have important practical implications, by informing the extent to which both positive and adverse experiences need to be considered if we are to promote cardiovascular health through childhood. Better understanding of modifiable resilience factors could provide targets for interventions to improve outcomes for children who may face adversity in the future or have experienced past adversities; offer important insights into the mechanisms underlying the relationships between childhood adversity and outcomes, and improve the tailoring of interventions to those who can most benefit from them. At a broader level, this study can contribute to shifting narratives in the childhood adversity field, away from a deficit-only and overly deterministic perspective.
Date proposal received: 
Friday, 21 August, 2020
Date proposal approved: 
Tuesday, 25 August, 2020
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cardiovascular risk, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Cardiovascular, Childhood - childcare, childhood adversity

B3606 - Genetic determinants of neonatal hyperbilirubinemia - 25/08/2020

B number: 
B3606
Principal applicant name: 
Connie Bezzina | Amsterdam UMC (The Netherlands)
Co-applicants: 
Najim Lahrouchi
Title of project: 
Genetic determinants of neonatal hyperbilirubinemia
Proposal summary: 

Neonatal jaundice is a yellowish discoloration of the eyes and skin in a newborn baby as a consequence of high bilirubin levels. While jaundice in most newborn is normal, a subset of patients with elevated bilirubin levels may develop excess sleepiness or poor feeding, whereas patients with excessive bilirubin levels are at risk for severe brain damage. In this project we aim to identify genetic risk factors for the development of high bilirubin levels in the newborn. This information can aid in risk prediction and the onset of early treatment for hyperbilirubinemia in the newborn.

Impact of research: 
If an association is found between genetic variants and neonatal hyperbilirubinemia, this finding would (1) provide an inroad for future risk prediction of hyperbilirubinemia and (2) has the potential to uncover novel biological pathways that play a role in hyperbilirubinemia.
Date proposal received: 
Tuesday, 25 August, 2020
Date proposal approved: 
Tuesday, 25 August, 2020
Keywords: 
Genetics, Hyperbilirubinemia, GWAS, Genetic epidemiology, Genetics, Genomics, Genome wide association study

B3601 - The genetic basis of acne vulgaris - 02/09/2020

B number: 
B3601
Principal applicant name: 
Josine Min | MRC Integrative Epidemiology Unit
Co-applicants: 
Dr. Jake Saklatvala, Professor Michael Simpson, Professor Catherine Smith
Title of project: 
The genetic basis of acne vulgaris
Proposal summary: 
Impact of research: 
Date proposal received: 
Wednesday, 19 August, 2020
Date proposal approved: 
Tuesday, 25 August, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Skin diseases - acne vulgaris, GWAS, Dermatology

B3602 - Linking observed mental health data with record linkage in ALSPAC - 21/08/2020

B number: 
B3602
Principal applicant name: 
Alex Kwong | IEU
Co-applicants: 
Dr Rebecca Pearson, Dr Dheeraj Rai, Dr Julian Walker, Andy Boyd, Ms Holy Fraser
Title of project: 
Linking observed mental health data with record linkage in ALSPAC
Proposal summary: 

The purpose of this project is to provide additional data for the project B3550 (antidepressant use and mental health) and collect new data as part of ALSPAC's mental health response to the COVID-19 pandemic. This data will allow further examinination for the ongoing mental health work by ASPAC and can be used alongside record linkage data to examine patterns of mental health before and during the COVID-19 pandemic. We are interested in examining if observed data from COVID-19 and the annual Questionnaire match patterns taken from health record data (i.e., are people who report poorer mental health accessing services). If these patterns do not match, it is important to determine why not and how people with poorer mental health are managing if not by accessing services. This will provide insights into alternative forms of treatment for poorer mental health in the pandemic. We have three main objectives. The first is to further describe patterns of mental health by building upon our earlier work using COVID 19 mental health data. The second is to link the observed mental health data with the health record linkage and examine outcomes from the COVID-19 pandemic. The third is to provide additional data for B3550.

Impact of research: 
Change how mental health is treated in response to COVID-19. We have already influenced policy so this will be an extension of this work.
Date proposal received: 
Wednesday, 19 August, 2020
Date proposal approved: 
Wednesday, 19 August, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3598 - Psychosocial mechanisms of persistent pain Expression of Interest - 28/08/2020

B number: 
B3598
Principal applicant name: 
Edmund Keogh | University of Bath (United Kingdom)
Co-applicants: 
Rachael Gooderman-Hill, Christopher Eccleston
Title of project: 
Psychosocial mechanisms of persistent pain: Expression of Interest
Proposal summary: 

The remit of the Advanced Pain Discovery Platform funding call is to better understand the mechanisms associated with pain. Our Expression of Interest is focused on psychosocial mechanisms of pain, and as part of this we wish to see how these impact on individuals across the lifespan. We wish to explore potential psychosocial correlates of pain, and build on work already conducted by members of our consortium on pain. Details of this project will be updated in due course.

Impact of research: 
To better understand the way in which psychosocial factors impact on the development of pain
Date proposal received: 
Monday, 17 August, 2020
Date proposal approved: 
Tuesday, 18 August, 2020
Keywords: 
Social Science, Pain, Statistical methods, Ageing, Cognition - cognitive function, Social science

B3597 - Resilience and Susceptibility to Chronic Pain in ALSPAC - 28/08/2020

B number: 
B3597
Principal applicant name: 
Anthony Pickering | University of Bristol (United Kingdom)
Co-applicants: 
Dr Jim Dunham, Dr Jon Brooks, Dr Tom Lancaster, Dr. Laura Corbin, Dr. Laura Howe, Prof. Christopher Eccleston, Prof. Rachael Gooberman-Hill, Prof. Emma Robinson, Prof. Ian Penton-Voak
Title of project: 
Resilience and Susceptibility to Chronic Pain in ALSPAC
Proposal summary: 

Pain which lasts for more than 3 months is termed chronic or persistent pain. It often occurs in the absence of obvious injury. It can be very difficult to treat. The UK is home to several large databases that contain information about subjects’ life history of pain and their genetic “make-up”. We plan to use the largest of these (UK Biobank) to help identify the genes that are related to the presence of a chronic pain condition (e.g. pain of duration >3 months) and the related symptoms experienced by sufferers e.g. low mood, poor sleep, lack of motivation, (pain) anxiety or pain depression. By gaining confidence that these genetic markers are related to the presence of a chronic pain condition, we will then use this information to recruit two small (each <200) groups of ALSPAC subjects who may or may not already have a pain condition. The beauty of this approach, is that by identifying the genes that make people susceptible to developing a pain condition, we will see how this interacts with health factors e.g. weight, blood pressure, and events that shape a person’s psychology e.g. adverse life events such as bereavement, to try to provide a means for people to modify their risk, or identify people for whom early intervention might be most beneficial following an injury – to hopefully avoid them going on to suffer life-long pain.

To achieve this goal, we would ask those subjects to undergo a series of pain tests (which of themselves cause only temporary discomfort) and undergo an MRI scan of their brain and spinal cord.

To better characterise pain present in the ALSPAC cohort, we propose to add pain-specific questionnaires (and tasks) to the upcoming age 30 clinics and questionnaires, which would target all participants. These questionnaires/tasks would explore the incidence of pain in the cohort, which will provide a more complete picture than is currently available. By adding information to this time point, we will gain insight to the cohort and to which genetic and biological factors can influence the development of a chronic pain condition. The availability of this window, where the majority of the cohort are still (hopefully) pain-free, will provide a baseline from which future studies will be able to reflect on the factors that ultimately led some participants to develop a chronic pain condition.

Impact of research: 
1. Defining a polygenic risk score for chronic pain, if validated, will aid in the future delivery of personalised patient care. 2. The PRS with MR PheWAS can suggest causality and directionality enabling better understanding of the complex relationships between pain and psychosocial influences. 3. The recall arm will determine if high and low risk individuals, identified via the PRS, have altered pain processing in the absence of chronic pain. This will informed understanding on the development of chronic pain and could well aid in delivery of personalised patient care. 4. Inclusion of a set of standard pain (and pain related) questionnaires within the ALSPAC cohort will create a resource to the pain community of international importance.
Date proposal received: 
Friday, 14 August, 2020
Date proposal approved: 
Tuesday, 18 August, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pain, As described above: PRS and MR-PheWAS QST, CPM and Imaging New Questionnaires, Genetic epidemiology

B3599 - G1 Substance Use questions for the next sweep - 25/08/2020

B number: 
B3599
Principal applicant name: 
Jon Heron | UOB (United Kingdom)
Co-applicants: 
Title of project: 
G1 Substance Use questions for the next sweep
Proposal summary: 

We would like to find some additional data collection for the G1 cohort

These data would facilitate the continued longitudinal modelling of G1 substance use into adulthood
and be particularly useful in the event we are successful in the MRC grant we submitted in May 2020.

Impact of research: 
Date proposal received: 
Tuesday, 18 August, 2020
Date proposal approved: 
Tuesday, 18 August, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc.

B3595 - Assessing the contribution of poylgenic risk to pediatric lipid levels and longitudinal trends - 14/08/2020

B number: 
B3595
Principal applicant name: 
Shoa L. Clarke, MD, PhD | Stanford University (United States)
Co-applicants: 
Themistocles Assimes, MD, PhD
Title of project: 
Assessing the contribution of poylgenic risk to pediatric lipid levels and longitudinal trends
Proposal summary: 

Genetic studies have found connections between a person's genes and their cholesterol. These studies have been conducted in adults. Cholesterol is much less variable during childhood. We aim to see if the associations seen in adults also extend to children.

Impact of research: 
This work will lead to a better understanding of the polygenic contributions to complex traits, and it will have important implications for defining the emerging entity of "polygenic familial hypercholesterolemia."
Date proposal received: 
Wednesday, 12 August, 2020
Date proposal approved: 
Friday, 14 August, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Dyslipidemia and hypercholesterolemia, Statistical methods, Genetic epidemiology

B3596 - Pubertal development and psychobiological health - 14/08/2020

B number: 
B3596
Principal applicant name: 
Samantha Dockray | University College Cork (Ireland)
Co-applicants: 
Yvonne Nolan, Jenny Cooney, Eadaoin Whelan, Eithne Hunt
Title of project: 
Pubertal development and psychobiological health.
Proposal summary: 

During adolescence there are changes in how adolescents experience and regulate their emotions, and this is related, in part by changes in the body related to puberty and development of the neuroendocrine system. These changes can begin at different ages for people, and can also be influenced by the general physical health of the person, as well as their life experience of stress, social relationships and learning opportunities. Physical health influences psychosocial development in several ways, and there is an accumulation of evidence that biomarkers of physical health, including markers of inflammation, cortisol levels, and other indicators of stress, influences when, and how, adolescents develop skills in emotional regulation and stress management. There is a related body of evidence that puberty, inflammation and stress interact to influence emotional experience in childhood and adolescence, and may influence mood, and the risk of mod disorders, for example anxiety and depression. Much of the research on the psychobiological predictors, correlates and consequences of mood and behaviour have been done with adults, and so there is still much to know about if and how adolescent development may be influenced by inflammation, biomarkers of stress and experiences, and further, how these interactions may be influenced by pubertal development.

Impact of research: 
Understanding the interaction of pubertal development, inflammation, and stress during adolescence may provide insight into vulnerabilities to poor psychobiological health and mood disorders, and how these may vary according to the physical health and health behaviours of the person. Determining the associations of pubertal development and physiological indicators of health and inflammation, if any, will provide insight into how biomarkers of stress and inflammation and psychological wellbeing are related. Mapping these associations may provide indications of if and how prevention and intervention programs to support positive psychobiological health across childhood and adolescence.
Date proposal received: 
Thursday, 13 August, 2020
Date proposal approved: 
Friday, 14 August, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Speech/language problem, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Sex differences, Sleep, Blood pressure, BMI, Cardiovascular, Hormones - cortisol, IGF, thyroid, Metabolic - metabolism, Psychology - personality, Physical - activity, fitness, function, Puberty

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