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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B3428 - Epigenetic trajectories of mental health - 19/12/2019

B number: 
B3428
Principal applicant name: 
Esther Walton | University of Bath
Co-applicants: 
Title of project: 
Epigenetic trajectories of mental health
Proposal summary: 

Mental illness accounts globally for one third of years lived with disability, leading to tremendous loss of human, societal and economic potential. Most symptoms (e.g., depression, anxiety, conduct problems) emerge before adulthood, highlighting the first two decades of life as an important period of heightened vulnerability. Epigenetics has emerged as a biological system that captures the underlying genetic and environmental risk factors, but we do not yet understand the developmental dynamics in this system over time. Such knowledge, however, is critical if we are to understand how mental health disorders develop, and thus how they may be prevented.

Impact of research: 
Findings could lend novel insights into the epigenetic landscape of child psychiatric symptoms.
Date proposal received: 
Tuesday, 10 December, 2019
Date proposal approved: 
Monday, 16 December, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Microarrays, Biological samples -e.g. blood, cell lines, saliva, etc., Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Epigenetics, Genetics

B3430 - Liver measures in F30 clinic - 10/01/2020

B number: 
B3430
Principal applicant name: 
Kushala Abeysekera | Population Health Sciences (United Kingdom)
Co-applicants: 
Professor Matthew Hickman
Title of project: 
Liver measures in F@30 clinic
Proposal summary: 

Liver disease remains the only disease where mortality is rising in the UK. Alcohol-related liver disease (ARLD) and non-alcoholic fatty liver disease (NAFLD) are the two commonest indications for liver transplantation in this country.

ALSPAC analysed the prevalence of these diseases in the F@24 clinic using a modality called transient elastography, also known as Fibroscan. This gives measurement on how fatty the liver is (steatosis) and how scarred it is (fibrosis). This demonstrated over 1 in 5 participants had NAFLD, with 1 in 40 having evidence of fibrosis. Individuals with harmful drinking patterns AND obesity were at greatest risk of fibrosis. This is all the more alarming as ARLD and NAFLD tend to be diseases that manifest in the 4th and 5th decade.

ALSPAC has an opportunity to be, to the best of our knowledge, the only birth cohort to sequentially assess its participants for liver disease. We are proposing to re-assess the participants that remain in the G1 cohort for liver disease to see if there has been a progression in the number of cases seen. This would be one of the first attempt to map the development of liver disease in the general population setting.

Impact of research: 
Young adults are an poorly phenotype demographic for liver disease and remaina a clinic blind spot. If we unearth a larger prevalence of liver disease, particularly fibrosis, this could support primary care screening measures for young people with risk factor profiles.
Date proposal received: 
Wednesday, 11 December, 2019
Date proposal approved: 
Monday, 16 December, 2019
Keywords: 
Clinical research/clinical practice, Obesity, Medical imaging, Cohort studies - attrition, bias, participant engagement, ethics

B3426 - The longitudinal association between childhood sleep disturbances and psychotic experiences in adulthood - 03/12/2019

B number: 
B3426
Principal applicant name: 
Andrew Thompson | University of Warwick
Co-applicants: 
Mrs Latoya Clarke, Dr Katharine Chisholm, Professor Stanley Zammit, Professor Barnaby Nelson
Title of project: 
The longitudinal association between childhood sleep disturbances and psychotic experiences in adulthood
Proposal summary: 

Sleep disturbances during childhood are common and often resolve spontaneously without intervention (Touchette et al., 2005; Galland et al., 2012). However, those that are persistent and frequent have been shown to be associated with the development of later psychopathology including psychotic like experiences (Jeppesen et al., 2014). Previous research exploring data from the Avon Longitudinal Study of Parents and Children has shown that children, aged 2.5 and 9 years old, experiencing frequent nightmares were more likely to report psychotic experiences at age 12 (Fisher et al., 2014). Similarly, nightmares at 12 years old was also found to be associated with an increased risk of psychotic experiences at aged 18 (Thompson et al., 2015). Such findings suggest that nightmares during childhood may represent an important and clinically significant indicator for risk of psychotic experiences in adolescence.

The relationship between childhood sleep disturbances and the presence of psychotic experiences beyond the age of 18 is still yet to be understood. Research has shown that the incidence of psychotic experiences often peaks during adolescence to early adulthood (McGrath et al., 2016) and sleep disturbances frequently co-occur with psychotic like experiences during this time (Taylor et al., 2015). Consequently, understanding which early sleep problems present as a risk factor for the development of later psychotic experiences is key. This project will explore the longitudinal associations between childhood and adolescent sleep problems between the ages of 2.5 - 17 years old and self-reported psychotic experiences at 24 years old.

Fisher, H.L., Lereya, S.T., Thompson, A., Lewis, G., Zammit, S. and Wolke, D., 2014. Childhood parasomnias and psychotic experiences at age 12 years in a United Kingdom birth cohort. Sleep, 37(3), pp.475-482.
Galland, B.C., Taylor, B.J., Elder, D.E. and Herbison, P., 2012. Normal sleep patterns in infants and children: a systematic review of observational studies. Sleep medicine reviews, 16(3), pp.213-222.
Jeppesen, P., Clemmensen, L., Munkholm, A., Rimvall, M.K., Rask, C.U., Jørgensen, T., Larsen, J.T., Petersen, L., van Os, J. and Skovgaard, A.M., 2015. Psychotic experiences co‐occur with sleep problems, negative affect and mental disorders in preadolescence. Journal of Child Psychology and Psychiatry, 56(5), pp.558-565.
McGrath, J.J., Saha, S., Al-Hamzawi, A.O., Alonso, J., Andrade, L., Borges, G., Bromet, E.J., Oakley Browne, M., Bruffaerts, R., Caldas de Almeida, J.M. and Fayyad, J., 2016. Age of onset and lifetime projected risk of psychotic experiences: cross-national data from the World Mental Health Survey. Schizophrenia bulletin, 42(4), pp.933-941.
Taylor, M.J., Gregory, A.M., Freeman, D. and Ronald, A., 2015. Do sleep disturbances and psychotic-like experiences in adolescence share genetic and environmental influences?. Journal of Abnormal Psychology, 124(3), p.674.
Thompson, A., Lereya, S.T., Lewis, G., Zammit, S., Fisher, H.L. and Wolke, D., 2015. Childhood sleep disturbance and risk of psychotic experiences at 18: UK birth cohort. The British Journal of Psychiatry, 207(1), pp.23-29.
Touchette, É., Petit, D., Paquet, J., Boivin, M., Japel, C., Tremblay, R.E. and Montplaisir, J.Y., 2005. Factors associated with fragmented sleep at night across early childhood. Archives of pediatrics & adolescent medicine, 159(3), pp.242-249.

Impact of research: 
This research will highlight whether childhood sleep disturbances represent an early risk factor for the development of psychotic experiences in adulthood. This will extend previous research which has shown childhood sleep disturbances to be related to psychotic experiences during adolescence (Fisher et al., 2014; Thompson et al., 2015). The proposed project will further what we know about the importance of early childhood experiences in the development of adulthood mental health experiences.
Date proposal received: 
Tuesday, 3 December, 2019
Date proposal approved: 
Tuesday, 3 December, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Sleep

B3425 - Does socioeconomic position modify associations between grandparental body composition and that of the grandchildren - 04/12/2019

B number: 
B3425
Principal applicant name: 
Christina Catherine Dahm | Aarhus University (Denmark)
Co-applicants: 
Jie Zhang, MPH, Professor Debbie Lawlor
Title of project: 
Does socioeconomic position modify associations between grandparental body composition and that of the grandchildren?
Proposal summary: 

The worldwide prevalence of obesity has tripled since 1975, and nearly a third of the world's population is now classified as overweight or obese. This rising prevalence of obesity is not only due to single genetic or environmental factors, but largely attributed to complex gene-environment interactions. Genetically predisposed individuals may be more prone to obesity in an obesogenic environment. Previous studies have focused on the identification of specific environmental factors that interact with genetic predisposition to obesity. The results indicate that physical activity, diet, age, gender and ethnicity could modulate the risk for obesity. Socioeconomic position (SEP) is relevant to all realms of behaviors and lifestyles, is a key factor that determines health across the lifespan, and may carry over to subsequent generations. The fact that BMI inequalities have persisted across different generations means that SEP is a significant factor to consider when understanding the role of environment. Parental SEP could influence the offspring’s risk of obesity through shared lifestyles such as dietary profile, home environment, social networks, and physical activity patterns early in life, which may be exacerbated by predisposition to obesity. Emerging studies have started to focus on SEP mobility across the life course, or intergenerational SEP mobility across two generations. The findings show evidence that higher parental education may be favorable in lowering obesity risk in offspring, especially for women. Longitudinal research should minimize reverse causation and allow us to investigate the dynamic interplay between one’s social strata of origin and own achieved social strata on obesity. However, it is still unclear how early the ancestors’ influence emerge and to what extent susceptibility to obesity is attenuated by SEP mobility.
We hypothesize that higher grandparental SEP, and upward SEP mobility across generations would diminish the grandchildren’s risk of obesity, compared to those who are always in social disadvantaged strata. The approach to consider ancestors’ SEP as a modifier in the heritability of BMI will add in tailoring appropriate interventions in future work.

Impact of research: 
A better understanding of the etiology of obesity and the related risk factors will help to identify possible preventative strategies. Parental SEP has immediate and long-term effects on children’s health. More evidence suggests that we need to move the emphasis from traditional risk factors to ‘upstream’ factors. In particular, this applies to the socioeconomic determinants of health. Minimizing social inequities through effective policy would offer an important opportunity to prevent the development of risk factors and consequent disease. The development and implementation of obesity prevention strategies could target factors contributing to obesity in social disadvantage groups. To conclude, the results from the study will add new evidence to the national and international research in this area.
Date proposal received: 
Monday, 2 December, 2019
Date proposal approved: 
Tuesday, 3 December, 2019
Keywords: 
Epidemiology, Obesity, Statistical methods, BMI

B3424 - Is normal variation in brain activity during sleep related to liability for schizophrenia - 10/12/2019

B number: 
B3424
Principal applicant name: 
Matt Jones | University of Bristol, School of PPN (UK)
Co-applicants: 
Nicholas Timpson
Title of project: 
Is normal variation in brain activity during sleep related to liability for schizophrenia?
Proposal summary: 

Different parts of our brains communicate with one another as we learn new information during the day, then continue to communicate “offline” as we sleep. This overnight brain activity helps file memories for long-term storage, but the process is complex and delicate: lots of genes influence brain activity in ways we do not yet understand. We also need to establish why and how this process is disrupted in disorders like schizophrenia, which are associated with impaired sleep-dependent brain activity and memory. This study will investigate links between a set of schizophrenia-associated genes and brain function during sleep.

Participants will be asked to wear a ‘fitbit’-like device for 2 weeks of normal activity, so we can track when and how much they sleep. We will then use a comfortable sleep cap that contains an array of recording devices to monitor EEG brainwaves while participants sleep at home for 2 nights. By analysing the EEG data using machine learning methods (similar to those used for speech recognition), we will identify patterns of activity that make up their personal “sleep fingerprint”. This will allow us to test whether these fingerprints vary according to genetics in a healthy population, without interference from things like medication that complicate patient studies.

The main outcomes will be (1) development of novel analysis methods allowing us to capture brain activity, (2) a deeper understanding of the mechanisms that determine variation in patterns of brain activity during sleep and (3) a route towards understanding mechanisms of schizophrenia liability.

Impact of research: 
Given the complexity of interwoven levels linking genetics to brain-wide connectivity and function, how best to map genomic information to a neurobiological understanding of schizophrenia? Sleep neurophysiology presents a uniquely powerful opportunity to bridge these levels of analysis. Psychiatric genetics has catalogued hundreds of risk-associated variants, and will continue to inform our interpretations of complex brain disorders as sample sizes expand and omics advances. However, neuropsychiatric disorders still cause untold global suffering – we urgently need to bridge genomics to pathophysiological pathways and rational therapeutic design. We believe interdisciplinary collaborations like our own are an indispensable part of this effort.
Date proposal received: 
Wednesday, 27 November, 2019
Date proposal approved: 
Friday, 29 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Computer simulations/modelling/algorithms, Cognition - cognitive function

B3421 - Brain signatures of adolescent depression and depression risk - 29/11/2019

B number: 
B3421
Principal applicant name: 
Heather Whalley | University of Edinburgh
Co-applicants: 
Professor Andrew McIntosh, Professor Nic Timpson, Mr Alex Kwong, Ms Miruna Barba, Dr Liana Romaniuk
Title of project: 
Brain signatures of adolescent depression and depression risk
Proposal summary: 

Population-based genetic and imaging studies of depression in adults have greatly advanced our understanding of this leading cause of global disability, particularly regarding associated neurobiological features. However, the causes and timings of such brain changes remain unknown, highlighting the need for a targeted study of the origins of these differences in younger individuals.

The largest risk factor for depression is a positive family history, and the major risk period for its development is during adolescence. The current project will therefore investigate whether the origin of these imaging features in adults (from work in UK Biobank, Enigma and Generation Scotland) is seen earlier in life in relation to increased risk for the disorder (including family history, polygenic risk, and associated traits such as depressive cognition, locus of control and self-esteem) using genetic and imaging data from children and parents in ALSPAC. Only now are there adult samples of sufficient size to inform such a focused study of adolescent depression, and this will form the first step towards determining potential causative associations between risk factors, associated neurobiology and depressive symptoms.

Summary data from these investigations in future could be combined in meta-analyses with other cohorts (e.g. MoBa) and consortia for discovery and replication. This would be under strict governance structures, where data would remain in Edinburgh and no individual data would be shared and this would be the focus of a separate application.

Impact of research: 
This will be the first study using large population-based imaging data to inform origins of neurobiological features of depression during adolescence
Date proposal received: 
Tuesday, 26 November, 2019
Date proposal approved: 
Friday, 29 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Medical imaging, Psychology - personality

B3423 - Characterising the ALSPAC mothers who are also UKBiobank participants - 29/11/2019

B number: 
B3423
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
Alison Teyhan, Mark Mumme, Richard Thomas, Nic Timposn
Title of project: 
Characterising the ALSPAC mothers who are also UKBiobank participants
Proposal summary: 

Many of the ALSPAC mums and fathers/partners may have also volunteered to take part in the UK Biobank cohort study. It is important that the study Data Managers and the researchers understand who is in both studies. This is because studies such as ALSPAC and UKBiobank are often used together in order to study rare events or small associations (where you need large numbers of participants for the statistical tests to work) or they are used to check and confirm whether findings in one study are also seen in another study. Finding the same patterns means there can be more confidence the findings are genuine, rather than occurring by chance or due to error. In both cases, the statistical tests assume the people in one study are different to the people in the other study. However we now know there is substantial overlap between participants in ALSPAC and UK Biobank (and possibly other studies).

ALSPAC and UKBiobank are ensuring that any duplication is flagged so researchers can take account of this (without knowing the identities of the participants). To inform thinking on how to best deal with this issue, it is necessary to produce descriptive statistics describing the characteristics of the ALSPAC participants who are in UKBiobank and how these differ from ALSPAC participants who are not in UKBiobank.

Impact of research: 
To inform users of the ALSPAC and UKBiobank resources and to aid study managers plan additional research questions, methodological research, data collection and participant communications & engagement strategies based on the overlapping sample.
Date proposal received: 
Wednesday, 27 November, 2019
Date proposal approved: 
Friday, 29 November, 2019
Keywords: 
Epidemiology, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3418 - Neurobiological Mechanisms in Adolescent Marijuana Exposure and Schizophrenia Risk - 22/11/2019

B number: 
B3418
Principal applicant name: 
Beng-Choon Ho | University of Iowa Carver College of Medicine (United States of America)
Co-applicants: 
Prof. John Macleod, Andy Boyd
Title of project: 
Neurobiological Mechanisms in Adolescent Marijuana Exposure and Schizophrenia Risk
Proposal summary: 

Heavy marijuana (MJ) use in adolescence has been associated with 2-4 fold increased risk for schizophrenia (SZ) in later life. It is unclear if lighter and more sporadic MJ exposure (i.e. recreational MJ use), a pattern more typical of most adolescent users, has similar deleterious effects especially when more potent forms of MJ have become the norm during the past 2 decades. In a recently completed 3-year longitudinal study, we found that unaffected adolescent first-degree biological relatives of schizophrenia patients with recreational MJ use failed to show age-expected maturation in processing speed and executive functioning and in pruning of gray matter cortical thickness within dorsolateral prefrontal and parieto-temporal brain regions. The overall objective of this ALSPAC proposal are to understand the nature of the association between adolescent recreational MJ use and schizophrenia susceptibility. The specific aims are to delineate the impact of adolescent recreational MJ use on cognitive maturation, brain cortical development and its specificity on risks for developing schizophrenia and other common psychiatric disorders in later life.

Impact of research: 
If exposure to low levels of high potency forms of marijuana during adolescence heightens the risk for schizophrenia later in life, such a finding will have important public health implications. Counseling adolescents against heavy adolescent marijuana use may no longer be sufficient if recreational use is no longer “safe”. New public health policies to reduce marijuana use among adolescents may therefore be necessary. Reduced adolescent exposure to high potency MJ may also lead to lower SZ incidence. Another likely impact of this research is advancing understanding regarding the neurobiological mechanisms that underlie how adolescent marijuana use may increase susceptibility for schizophrenia through disruptions in adolescent brain maturation. Such novel findings from this proposal will bolster vital foundational knowledge for the development of new therapeutic measures to help reduce the severe disease burden of schizophrenia.
Date proposal received: 
Wednesday, 20 November, 2019
Date proposal approved: 
Friday, 22 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Cognitive assessments, questionnaires, brain MRI scans, data linkage to healthcare records of psychiatric diagnoses, Cognition - cognitive function, Development

B3417 - The effect of the perceived environmental surroundings on face shape at 15 years of age - 22/11/2019

B number: 
B3417
Principal applicant name: 
Stephen Richmond | Cardiff University (UK)
Co-applicants: 
Ler Chong, Dr Damian Farnell
Title of project: 
The effect of the perceived environmental surroundings on face shape at 15 years of age.
Proposal summary: 

This project will explore the perception of environmental conditions on the face shape of 15 year old children.

The question that will be addressed does environmental surroundings influence face shape?

Impact of research: 
Any findings between face and environment are likely to be subtle.
Date proposal received: 
Wednesday, 20 November, 2019
Date proposal approved: 
Friday, 22 November, 2019
Keywords: 
Face shape, Face shape, Face shape analyses, Face - face shape

B3415 - Investigating the role of genetics in the obese-asthma phenotype in children - 21/11/2019

B number: 
B3415
Principal applicant name: 
Raquel Granell | MRC Integrative Epidemiology Unit (IEU), University of Bristol (England )
Co-applicants: 
Dr. Cristina Longo, Dr. Anke-Hilse Maitland van der Zee
Title of project: 
Investigating the role of genetics in the obese-asthma phenotype in children
Proposal summary: 

We now know that children who have asthma and are also obese are more likely to require an urgent visit to the doctor for breathing problems than those who are not obese. Obese children are thought to have a different type of asthma, which is more severe and harder to control. This may be because the current treatments we use to manage daily symptoms do not work very well for this type of asthma. There are many theories that could explain why this is happening. One possible reason could be that the child’s genetic makeup may also play a role in the development of obesity as well as influence their response to treatment.

To address this problem, my proposed project aims to investigate how obesity can affect the response to treatment in children with asthma. In the first phase, I will examine whether obese children with asthma are less likely to respond to standard treatments than those who have normal weight using cutting-edge statistical methods. In the second phase, I will investigate whether certain genetic changes influence the children’s ability to respond to asthma treatments and if these same changes are also affected by excess weight.

To do this, I will analyze data that has already been collected from a large number of children with asthma in many different countries, including ALSPAC. The data that will be used for this project forms part of an international collaboration in pediatric asthma, called the Pharmacogenomics in Childhood Asthma (PiCA) Consortium. PiCA is the largest pediatric asthma consortium in the world and has all the necessary data to successfully carry out this research.

I expect the results of this project to help doctors and scientists understand why obese children with asthma are suffering with more severe symptoms than others. Identifying the reasons why they are severe will promote the development of new targeted treatments for children with asthma who have excess weight, with the ultimate goal of improving the management and quality of life for these children.

Impact of research: 
Date proposal received: 
Wednesday, 20 November, 2019
Date proposal approved: 
Thursday, 21 November, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Obesity, Respiratory - asthma, Statistical methods, BMI, Genetic epidemiology, Mendelian randomisation

B3416 - Investigating a DNA methylation signature of e-cigarette use - 29/11/2019

B number: 
B3416
Principal applicant name: 
Rebecca Richmond | University of Bristol (UK)
Co-applicants: 
Matthew Suderman, Paul Yousefi, Marcus Munafo, Caroline Relton, Suzanne Gage
Title of project: 
Investigating a DNA methylation signature of e-cigarette use
Proposal summary: 

Electronic cigarettes (e-cigarettes) have the potential to reduce the harm caused by smoking, but there is currently little information regarding their long-term safety. We propose a novel methodology to quantify aspects of the biological (specifically epigenetic) changes associated with e-cigarette use, and the extent to which these changes are associated with future disease risk. We will determine whether e-cigarette users (“vapers”) are more comparable to smokers of tobacco cigarettes or to never-smokers with respect to their epigenetic signature. We will then determine whether the epigenetic profile associated with e-cigarette use differentially predicts risk of disease, and whether these epigenetic changes are causally linked to disease, and as such may be targets for preventative interventions. This research will provide key scientific insights, as well as valuable information to both cigarette smokers and vapers regarding the relative safety of these products in relation to their biological impact and future disease risk.

Impact of research: 
These results will be of direct relevance to health professionals and policy makers. If we find vaper methylation patterns similar to those of smokers, this might indicate that long-term health risk is similar. If, conversely, e-cigarette methylation patterns are more akin to patterns seen in non-smokers, this might provide evidence that their use as a smoking-cessation device could be encouraged. This information is important to governments and organisations making e-cigarette policy and legislation decisions.
Date proposal received: 
Wednesday, 20 November, 2019
Date proposal approved: 
Thursday, 21 November, 2019
Keywords: 
Epigenetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, epigenome-wide association study, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics

B3414 - The Association between the Natural Environment and Emotional Social and Behavioural Development - 02/12/2019

B number: 
B3414
Principal applicant name: 
Dr Benedict Wheeler | University of Exeter (UK)
Co-applicants: 
Mr Mark Ferguson, Dr Alison Teyhan, Dr Rosie McEachan, Dr Rebecca Lovell , Mr Andy Boyd, Prof John Macleod
Title of project: 
The Association between the Natural Environment and Emotional, Social and Behavioural Development
Proposal summary: 

Exposure to natural environments has been shown to be associated with child development and outcomes later in life. This will be investigated by measuring exposure to the natural environment using a combination of linked spatial environmental indicators and self-reported data. For example, normalized difference vegetation index (NDVI) measurements will be used alongside subjective measurements of parks visits and outdoor time. This will assess exposure multi-dimensionally, by measuring how much an individual visits natural environments as well as the abundance of vegetation in their living environments.

The primary outcome of interest will be emotional, social and behavioural development, primarily assessed using the Strengths and Difficulties Questionnaire. It will be assessed at multiple time points and corroborated from parent and teacher-reported sources. Other mental wellbeing/developmental measures will be used as secondary outcomes. The project will also investigate potential intermediate variables such as air pollution, maternal wellbeing, biomarkers of stress and birth outcomes. Access to the natural environment is often distributed
by social class / socio-economic status. Therefore detailed and multiple dimensional indicators will be used to account for confounding.

Impact of research: 
The primary impact of this research will be to develop the evidence base on the connection between natural environments/ Greenspace and childhood development. Many studies in the field have been cross-sectional. Therefore adding a study with highly detailed temporal data will enhance the evidence base, particularly if submitted for publication in a high-quality journal. The variables available within ALSPAC will allow for the development of greenspace exposure metrics beyond what is often used in greenspace and health studies. This will help to understand which metrics (i.e. geospatial or self-reported metrics) are most appropriate; it will enable a greater understanding of what aspect(s) of the natural environment are likely to influence child development. For example, whether active usage or passive exposure is more prominent and at which stages of the life course may be more sensitive. Utilising this data will be impactful for ALSPAC and PEARL and display the increasing potential of linking cohort studies to geospatial data temporally.
Date proposal received: 
Tuesday, 19 November, 2019
Date proposal approved: 
Thursday, 21 November, 2019
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Development, Environment - enviromental exposure, pollution

B3411 - Using genetically informed designs to disentangle depression - 19/11/2019

B number: 
B3411
Principal applicant name: 
Alex kwong | UoB / IEU / Uni of Edinburgh
Co-applicants: 
Dr Mark Adams, Professor Andrew McIntosh
Title of project: 
Using genetically informed designs to disentangle depression
Proposal summary: 

Genome-wide association studies (GWAS) have been instrumental in highlighting associations between genetic variants and 1000s of traits. A recent GWAS of major depressive disorder (MDD) by the psychiatric genetics consortium (PGC) has recently identified 102 genetic variants associated with the disorder (Howard et al., 2019). In ALSPAC, genetic liability (indexed by polygenic risk scores) are associated with depression and numerous mood disorder phenotypes. However, genetics are only one side of the story and the interplay between genetic liability and environmental risk factors in the onset and maintenance of depression and related mood disorders is still unclear.

The data will be created by AK and will require a collaborator ID and DAA to have the data stored in Edinburgh on the secure server.

Impact of research: 
elucidate pathways to depression
Date proposal received: 
Friday, 15 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3409 - The effect of early life exposures on body mass index from early childhood to early adulthood - 19/11/2019

B number: 
B3409
Principal applicant name: 
Tim Cadman | IEU, Bristol University
Co-applicants: 
Professor Deborah Lawler, Dr Ahmed Elhakeem, Johan Lerbech Vinther, Serena Fossati, Anne-Marie Nybo Andersen, Kate Northstone
Title of project: 
The effect of early life exposures on body mass index from early childhood to early adulthood
Proposal summary: 

Reducing childhood obesity is a major global public health challenge. However, interventions designed at changing individual or family behaviours often do not show an impact. It is important therefore to better understand the causes of childhood obesity. Whilst there is some evidence that factors in pregnancy are associated with obesity, it is unclear whether these are causes. It is also unclear whether different factors affect obesity at different ages.

For example, there is evidence that children whose mothers had gestational diabetes may have a greater risk of childhood obesity. Studies in Europe and South Asia have also reported that this effect may not emerge until later on in childhood. There is also evidence that infants born preterm are about two-fold more likely to be obese later in life than those born at term. However few studies have examined the association between preterm birth and BMI in later childhood.

In terms of socioeconomic factors, lower family socioeconomic position (SEP) has been associated with higher BMI from as early as 9 months. However, there is inconsistent evidence on the extent as to whether which the effect of SEP increases, decreases or remains constant over time. There is also evidence that neighbourhood exposures in the post-natal period (such as exposure to green spaces and area-level deprivation) are also associated with childhood BMI; however to our knowledge the effect of these exposures before birth has not been investigated.

The LifeCycle project is an EU initiative to harmonise key data from a number of EU studies, including ALSPAC. To maintain participant anonymity, we will be using innovative software called DataSHIELD to analyse the data. DataSHIELD allows the remote analysis of summaries of this harmonised data, but prevents the access of individual data.

The LifeCycle project provides a unique opportunity to examine how early life factors might relate to childhood BMI. In this ‘proof of principle’ study we will use DataSHIELD to carry out remote analyses of LifeCycle cohorts, selecting variables that have evidence for some effect on childhood BMI (maternal and paternal education, area level deprivation, access to greenspace, gestational diabetes and gestational age at birth). We will conduct analysis on BMI at different points throughout childhood to explore how the effect of these factors emerges over childhood.

Impact of research: 
Date proposal received: 
Thursday, 14 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Epidemiology, Obesity, Statistical methods, BMI

B3413 - The role of the glycocalyx in cardiovascular and pregnancy health - 22/11/2019

B number: 
B3413
Principal applicant name: 
Deborah Lawlor | MRC IEU at the University of Bristol (United Kingdom)
Co-applicants: 
Prof Simon Satchell, Dr Victoria Bills, Dr Colin Down, Dr Tom Richardson
Title of project: 
The role of the glycocalyx in cardiovascular and pregnancy health
Proposal summary: 

The glycocalyx is a gel-like layer covering the inside surface of all blood vessels. It is essential for normal flow and activity of the blood. Laboratory studies suggest damage to the glycocalyx increases risk of heart disease and pregnancy complications such as preeclampsia, gestational hypertension, gestational diabetes, small and large for gestational age and preterm delivery. Glycocalyx could be a valuable target for disease prevention and treatment. We do not have studies in large numbers of humans that use methods which could help us understand the causal effects of the glycocalyx. The clycocalyx can be measured in two ways: (i) measures in stored blood samples of molecules that are inside the glycocalyx but are shed into the blood when it is damaged (e.g. heparin sulphate proteoglycans, hyaluronic acid and syndecan 1 (SND1) and (ii) microscopic measurement of of small blood vessues under the tongue. We want to add both of these types of measurements to ALSPAC to improve our understanding of how the glycogalix could influence health and well being in pregnancy, during childhood and in adulthood.

Impact of research: 
Increased understanding of the role of the glycocalyx on cardiovascular and pregnancy health. Discovery of a potential target for preventing cardiovascular diseases and pregnancy disorders
Date proposal received: 
Tuesday, 19 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, BMI

B3412 - Environmental exposures in pregnancy and early life influencing cognitive and cardio-respiratory development - 24/11/2019

B number: 
B3412
Principal applicant name: 
Anna Hansell | University of Leicester, Centre for Environmental Health and Sustainability (United Kingdom)
Co-applicants: 
Miss Yingxin Chen, Miss Katie Eminson, Professor John Gulliver, Dr Calvin Jephcote
Title of project: 
Environmental exposures in pregnancy and early life influencing cognitive and cardio-respiratory development
Proposal summary: 

Exposure to air pollution and road transport noise in pregnancy and early life may affect development of heart, lung and cognitive function that have long-term effects into adult life. However, it is unclear how important this is as there are few studies on the impact of very early life exposures to environmental pollution

Impact of research: 
The findings of this project will provide new knowledge to inform UK and European policy, with relevance to design and placement of new housing, schools and roads, and to noise and air pollution abatement schemes. Dissemination will be through our existing links with the Noise and Nuisance Technical and Evidence Team at DEFRA, through candidate attendance at international conferences (International Commission for the Biological Effects of Noise conference in 2020 and the Internoise conference 2021) and publication of peer-reviewed journal papers. It is intended to publish results in high impact journals at the end of the project, which might contribute to policy decision-making and/or future follow-up studies.
Date proposal received: 
Monday, 18 November, 2019
Date proposal approved: 
Tuesday, 19 November, 2019
Keywords: 
Epidemiology, Developmental disorders - autism, Cognitive impairment, Diabetes, Hypertension, Learning difficulty, Mental health, Respiratory - asthma, Speech/language problem, CVDs, lung function, Computer simulations/modelling/algorithms, Statistical methods, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, Offspring, Parenting, Psychology - personality, Physical - activity, fitness, function, Social science, Speech and language, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Development, Environment - enviromental exposure, pollution, Growth, Intelligence - memory, Linkage

B3410 - Testing the role of relative age within school year on mental health in children with neurodevelopmental vulnerability - 24/11/2019

B number: 
B3410
Principal applicant name: 
Stephan Collishaw | Cardiff University (UK)
Co-applicants: 
Mr Tom Broughton, Professor Kate Tilling, Dr Kate Langley, Dr Richard Anney
Title of project: 
Testing the role of relative age within school year on mental health in children with neurodevelopmental vulnerability
Proposal summary: 

In England and Wales, the academic year begins in the September, and children start school in September before they are five years old. If children are born in September, then they are nearly five when they start school, but if they are born in August in the following chronological year then they have only just turned four years old when the school year starts. Studies have shown that the youngest children within a school year are at an increased risk for mental health problems, social impairment, neurodevelopmental disorder and intellectual disability diagnoses, and lower educational attainment (Bedard & Dhuey, 2006; Zoëga et al., 2012; Pottegård et al, 2014; Root et al., 2019). Cross-national comparisons of large representative population surveys that compare countries with different school entry dates have suggested that associations may reflect causal influences of age within school year on these outcomes, rather than season-of-birth (Goodman et al., 2003). This project will focus on children with early neurodevelopmental vulnerability, which will be defined using neurodevelopmental symptoms and diagnoses, genetic risk, or prematurity of birth. These children are all already at a higher risk of mental health problems including depression (Rice et al., 2018). We hypothesise that relative age effects may affect these groups of children more than others over development from childhood to adulthood. We also hypothesise that differences in mental health by month of birth will emerge only after school entry but show some persistence across the school years into early adulthood.

Impact of research: 
This project will likely be impactful as it aims to be assess whether age at school entry is causally associated with later mental health difficulties in specific at-risk groups. The project will help identify those children who are at highest risk of later mental health problems, and who are therefore a priority for early support and preventative intervention. Furthermore, identifying a group(s) of children who would benefit from delaying school entry has potentially significant individual, family and societal benefits. Currently, guidance in England and Wales indicates that it is possible to delay school entry if there is a ‘compelling reason’. However, decisions on deferred school entry are often left to individual school admission boards, and policy varies between the devolved nations. The project will provide comprehensive evidence on whether children at risk should be rigidly assigned to school entry based on date of birth or given greater flexibility regarding school entry, taking into account developmental maturity. Therefore, the findings of this project would be of significant interest to parents, carers, and teachers of premature children and children with neurodevelopmental disorders, as well as charities that advocate for these groups. The findings will also be of interest to the Welsh Government, UK Government, and local education authorities.
Date proposal received: 
Friday, 15 November, 2019
Date proposal approved: 
Sunday, 17 November, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Genetic epidemiology, Statistical methods

B3408 - International Cannabis Consortium - GWAMA of quantity/frequency of cannabis use - 14/11/2019

B number: 
B3408
Principal applicant name: 
Lindsey Hines | Population Health Sciences
Co-applicants: 
Dr Robyn Wootton, Dr Hannah Sallis, Professor Marcus Munafo
Title of project: 
International Cannabis Consortium - GWAMA of quantity/frequency of cannabis use
Proposal summary: 

The International Cannabis Consortium has been created to combine the results of multiple genome-wide association studies of different cannabis use phenotypes (e.g., lifetime use, age at initiation, frequency of cannabis use) in meta-analyses in order to increase the probability of detection of genetic variants associated with individual differences in cannabis use.

Impact of research: 
The consortium has published several successful GWAS meta-analyses over the years, including lifetime use and age at initiation. This it the first meta-analysis on the frequency of cannabis use. Frequency of use is a key determinant of the harms of cannabis use, and developing the GWAS for this phenotype is critical for understanding the relationship between cannabis and mental health.
Date proposal received: 
Wednesday, 13 November, 2019
Date proposal approved: 
Thursday, 14 November, 2019
Keywords: 
Genetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, GWAS, Genome wide association study

B3407 - Identifying genetic variants predisposing to overeating behaviour - 10/01/2020

B number: 
B3407
Principal applicant name: 
Fotios Drenos | Brunel University London and University College London
Co-applicants: 
Dr Terry Dovey
Title of project: 
Identifying genetic variants predisposing to overeating behaviour
Proposal summary: 

Obesity has been associated with a number of life threatening common diseases and is cited as the driving force behind poor health from early ages in both developing and developed countries. Obesity is the product of a complex interplay between our biology and our environment, with our behaviour playing a major role on how these interact. Previous studies have shown that targeted behavioural changes are effective obesity interventions for both short-term weight loss and long-term weight management. Although behaviour is a complex characteristic shaped by our culture, society and upbringing, similar to other complex human characteristics, it also has a genetic component that predisposes us to respond to environment cues in a specific manner. These genetic predisposition markers usually confer poor prediction of a specific individual’s complex phenotype or behaviour, but in larger population samples, they can provide information for existing patterns that can help us plan effective population level interventions and assess the causal patterns associated with them.

Impact of research: 
To identify the genetic predisposition of overeating and the markers predicting the behaviour. To use this information to better understand overconsumption and the potential behavioural interventions that can be used to avoid overeating and associated health problems.
Date proposal received: 
Monday, 11 November, 2019
Date proposal approved: 
Tuesday, 12 November, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Diabetes, Eating disorders - anorexia, bulimia, Obesity, Computer simulations/modelling/algorithms, GWAS, Metabolomics, BMI, Cardiovascular, Genetic epidemiology, Genome wide association study, Mendelian randomisation, Metabolic - metabolism, Psychology - personality

B3406 - Acceptability to participants of novel data linkages ethical issues and the practicalities of obtaining consent Evidence from - 21/11/2019

B number: 
B3406
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
Kate Shiells, Oliver Davis, Andy Skinner, Nic Timposn
Title of project: 
Acceptability to participants of novel data linkages, ethical issues, and the practicalities of obtaining consent: Evidence from
Proposal summary: 

This project will summarise and collate information gathered by ALSPAC and TwinsUK describing participant understanding and feelings towards 'novel' methods of data collection. This is in response to rapid changes in possibilities for data collection which are emerging from the rapid digitisation of routine information, that many people now routinely carry powerful computers (mobile phones, smart devices), and that many devices are now connected to the internet (e.g. smart doorbells and smart thermostats). There is potentially very valuable information which can be collected through either linking to individuals' records or by collecting the 'Digital Footprint' records left through using digital connected devices. In addition, these connected devices - e.g. mobile phones, or smart speakers - provide an opportunity to collect data in new ways.

It is vitally important that studies - such as ALSPAC and TwinsUK - understand participants views on this. This is so that studies can understand what is acceptable and what is not, what safeguards are needed to ensure acceptability, and how to inform participants about these new options and how they could work. This project is summarising existing information, it is not collecting any new information.

Impact of research: 
To inform funders and longitudinal studies about the potential for novel 'Digital Footprint' data sources and to emphasis the ethical and safeguard dimensions to this.
Date proposal received: 
Monday, 11 November, 2019
Date proposal approved: 
Monday, 11 November, 2019
Keywords: 
Statistics/methodology, study methodology, research ethics, data linkage., Qualitative study, Cohort studies - attrition, bias, participant engagement, ethics

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