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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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

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

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.

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.

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

B3594 - Large-Scale Genomic Analysis of Aging-Related Cognitive Change Prior to Dementia Onset - 14/08/2020

B number: 
B3594
Principal applicant name: 
Alex Kwong | UoB IEU
Co-applicants: 
Professor Nic Timpson, Dr Gail Davies, Professor Ian Deary
Title of project: 
Large-Scale Genomic Analysis of Aging-Related Cognitive Change Prior to Dementia Onset
Proposal summary: 

This project will provide the most comprehensive interrogation of the genetics of aging-related cognitive changes during prodromal, so-called “silent,” periods of ADRD progression. Identifying the genetic risk factors and mediating biological mechanisms underlying progression to Alzheimer’s disease and related dementias of aging is crucial to developing interventions to prevent, delay, or otherwise mitigate ADRD disease progression.

Impact of research: 
Greater understanding of the genetics underpinning cognitive decline.
Date proposal received: 
Wednesday, 12 August, 2020
Date proposal approved: 
Friday, 14 August, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Cognitive impairment, GWAS, Ageing

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

B3589 - The moderating role of genetic propensity in the relationship between depression/anxiety and substance use during Covid-19 era - 11/08/2020

B number: 
B3589
Principal applicant name: 
Jueun Kim | Chungnam National University
Co-applicants: 
Title of project: 
The moderating role of genetic propensity in the relationship between depression/anxiety and substance use during Covid-19 era
Proposal summary: 

Previous studies have reported that addictive behaviors decrease when infectious disease first occurs but increase as the disease continues. It shows that especially among health workers, the addiction problems can get even more serious compared to the period when the infectious disease did not occur. This study wants to examine predictive factors that are associated with addictive behaviors before and after Covid-19.

Impact of research: 
Date proposal received: 
Wednesday, 5 August, 2020
Date proposal approved: 
Tuesday, 11 August, 2020
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc.

B3593 - Genetic impact on youth vaping extending known genetic risk factors in smoking to vaping - 11/08/2020

B number: 
B3593
Principal applicant name: 
Meghan Chenoweth | Centre for Addiction and Mental Health, and the University of Toronto (Canada)
Co-applicants: 
Dr. Rachel Tyndale, Dr. Marcus Munafo, Alaa Alsaafin, Ahmed El-Boraie
Title of project: 
Genetic impact on youth vaping: extending known genetic risk factors in smoking to vaping
Proposal summary: 

Adolescents who smoke cigarettes are more likely to start vaping, and the reverse is also true: vaping can lead to smoking. In former smokers, vaping can also increase the risk for relapse back to smoking. While some young people report vaping to help them quit smoking, most continue to smoke resulting in dual use. The high rate of dual use suggests that vaping could prolong smoking and increase harms in young people who would have otherwise quit. Biomarker data show that dual users are exposed to higher levels of harmful chemicals known to cause tobacco-related illnesses compared to those who only smoke.

Genetic variation influences cigarette smoking. People with gene variants that increase the rate at which nicotine is inactivated smoke more cigarettes, have a higher risk for tobacco-related illnesses, and are less likely to quit, compared to people with slow nicotine metabolism. In ALSPAC, we propose to study whether youth smokers with genetically faster nicotine metabolism have a higher risk for becoming a dual user and continuing smoking once they start vaping. In former smokers, we will test whether faster nicotine metabolism increases relapse back to smoking among vapers. As a secondary goal, we will also test whether other genes, for example those that alter the response to nicotine in the brain, also influence the risk for vaping.

The reasons underlying the popularity of vaping and dual use among youth are not well understood, and our work will show whether genetic factors play a role.

Impact of research: 
Our work will provide insight into the genetic contributions to vaping, allowing for the identification of vulnerable sub-groups. Due to the nature of the genes under study, our work will also identify potential mechanisms underlying the high rate of dual use, and thus the persistence of smoking, in youth vapers. Because CYP2A6 variation predicts smoking cessation outcomes and can be used to optimize treatment, our work may also facilitate tailored approaches to quitting vaping.
Date proposal received: 
Monday, 10 August, 2020
Date proposal approved: 
Tuesday, 11 August, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, Genetic epidemiology

B3591 - Exploring the progression of mental illness Identifying predictors of recovery - 11/08/2020

B number: 
B3591
Principal applicant name: 
Robyn Wootton | University of Bristol
Co-applicants: 
George Davey Smith, David Kessler, Marcus Munafo, Andy Skinner, Kate Tilling, Alexandra Havdahl, Anne-Siri Oyen
Title of project: 
Exploring the progression of mental illness: Identifying predictors of recovery
Proposal summary: 

Depression is the leading cause of global disability with over 300 million people suffering world-wide. Estimates suggest that up to two thirds of patients do not recover following their first antidepressant treatment and up to one third do not recover after multiple treatments. Therefore, it is critically important to identify factors that predict recovery and reduce risk of relapse. Current methods in genetic epidemiology focus on predictors of mental illness onset. While this is crucial to prevent new diagnoses, it does little to help individuals already suffering. Therefore, the Recover project aims to extend current genetic epidemiology methods to better understand recovery from depression. The methods developed here will begin with a focus on depression but can also be extended to other mental illnesses. First, we will develop trajectories of depression using continuous longitudinal measures in two critical time points, 1) adolescence and early adulthood and 2) during and post pregnancy. Second, using these trajectories as outcomes we will explore many modifiable predictors of recovery. Third, we will use cutting-edge causal inference techniques to test whether or not these predictors are causal. And finally, we will develop novel technologies to capture fine-grained fluctuations in mood. Taken together, this work will lead to better interventions and inform adjuncts to treatment having real impact for the growing number of individuals suffering from depression.

Impact of research: 
With over 300 million people living with depression globally, it has been called a “mental illness epidemic”. Depression is the leading cause of disability worldwide, resulting in an estimated 800,000 suicides per year globally and 44 million lost years of productive life. Despite increased treatment provision, prevalence of depression has not decreased and up to a third of patients have still not responded after multiple treatments. Depression can bring immense suffering to both the individual afflicted and their family. Not responding to treatment can be both terrifying and frustrating. Given this significant burden that depression poses to both the individual and their families, strategies to promote recovery and prevent relapse are of upmost importance to public health. Therefore, it is critically important for patients that we identify factors that predict recovery and reduce the risk of relapse. Our proposed Recover project would have real impact for individuals with depression, their families and wider society.
Date proposal received: 
Thursday, 6 August, 2020
Date proposal approved: 
Tuesday, 11 August, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Genetic epidemiology

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