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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B3442 - The biological background of attention-deficit/hyperactivity disorder - 14/01/2020

B number: 
B3442
Principal applicant name: 
Hannah Sallis | MRC IEU
Co-applicants: 
Ville Karhunen, Gemma Sharp, Marcus Munafo, Claire Prince, Marjo-Riitta Järvelin
Title of project: 
The biological background of attention-deficit/hyperactivity disorder
Proposal summary: 

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by persistent patterns of inattention, hyperactivity and/or impulsivity, which interfere with normal functioning or development. ADHD is highly heritable, with heritability estimates from twin studies at around 75%. It is also suggested that epigenetic modifications – alterations in the DNA not changing the sequence itself – play a role in ADHD aetiology. In addition, there is known shared genetic liability between obesity and ADHD. Maternal obesity is a known risk indicator for offspring ADHD, however it is not clear whether this is due to the shared genetic predisposition, or possible intrauterine mechanisms.

Impact of research: 
Adding information to the biological background of attention-deficit/hyperactivity disorder.
Date proposal received: 
Monday, 13 January, 2020
Date proposal approved: 
Tuesday, 14 January, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Epigenetics, Genetic epidemiology, Statistical methods

B3438 - Novel statistical methods for the analysis of high-dimensional epigenetic data - 10/01/2020

B number: 
B3438
Principal applicant name: 
Haeran Cho | University of Bristol (United Kingdom)
Co-applicants: 
Prof Kate Tilling, Dr Josine Min, Dr Claire Gormley, Prof Jonathan Rougier
Title of project: 
Novel statistical methods for the analysis of high-dimensional epigenetic data
Proposal summary: 

We propose to address the problem of handling large-scale genome-wide DNA methylation data. To this end, we will develop a novel technique for clustering DNA methylation (DNAm) sites which will aid reducing the complexity of the subsequent EWAS. For example, a DNAm site that is hypo-methylated in the smoker cohort but hyper-methylated in non-smoker one merits further analysis for significant association with smoking, while those sites exhibiting no difference in the two cohorts does not.
We will investigate the use of algorithms for large matrix factorisation under constraints to provide a natural clustering of DNAm sites, and study what statistical guarantee is achievable under which conditions. To verify the suitability of the proposed method, we propose to use the DNA methylation data available from ARIES.

Impact of research: 
The findings from the proposed study will help lay a solid foundation for addressing the additional challenges brought on by epigenetic data analysis include (i) handling of continuous exposures beyond discrete variables (e.g., smoker/non-smoker), and (ii) accounting for cell heterogeneity. In particular, further research into (ii) is highly relevant since samples are measured at bulk rather than at the single-cell level and the methylome obtained for each sample contains the signals aggregated from distinct cell types. Few existing methods can identify the risk-DNAm sites for each individual cell type, missing the opportunity to obtain finer-scale results in EWAS. We plan to address the above problems based on the insights gained from the proposed research.
Date proposal received: 
Thursday, 9 January, 2020
Date proposal approved: 
Friday, 10 January, 2020
Keywords: 
Statistics/methodology, DNA sequencing, Statistical methods, Genetic epidemiology, Genome wide association study, Statistical methods

B3440 - PLACENTA - 29/01/2020

B number: 
B3440
Principal applicant name: 
Abigail Fraser | University of Bristol (United Kingdom)
Co-applicants: 
Sue Ring, Prof Tony W Parks, Prof Janet Catov, Alix Groom, Chris Nellaker, Prof Brian Cox
Title of project: 
PLACENTA
Proposal summary: 

Few studies have examined a large number of placenta from general population samples. There are therefore many unanswered questions about the links between placental abnormalities and maternal and offspring health in pregnancy and beyond. ALSPAC is unique, with some 10000 stored placentas from the original ALSPAC pregnancies in the early 90s. We will generate pathology data on this collection and study placental findings in relations to short term health in mums and their offspring.

Impact of research: 
Date proposal received: 
Thursday, 9 January, 2020
Date proposal approved: 
Friday, 10 January, 2020
Keywords: 
Epidemiology

B3439 - A Consolidator Grant to Study the Developmental Trajectories of Physical and Mental Health Multimorbidity in Genetic High-Risk C - 31/01/2020

B number: 
B3439
Principal applicant name: 
van den Bree | Cardiff University (UK)
Co-applicants: 
Professor John MacLeod, Professor Mark Mon-Williams, Professor David van Heel, Professor Sir Michael Owen, Professor James Walters, Professor George Kirov, Professor Peter Holmans, John Wright, Dr Sarah Finer
Title of project: 
A Consolidator Grant to Study the Developmental Trajectories of Physical and Mental Health Multimorbidity in Genetic High-Risk C
Proposal summary: 

A subgroup of people in the population have a change in their genetic make-up that greatly increases their risk of physical disorder and psychiatric disorder. The medical consequences of these genetic changes are however still very poorly understood. Particularly, we don't really know how these changes lead to increased risk of combinations of physical and mental health problems over time. As presence of a physical or mental health problem increases risk of other ones developing, it is important to understand how and why this happens in this high-risk group. Because these genetic changes are rare, it is important to bring together large samples to study their role in medical outcomes properly. This is particularly important if we want to understand how these changes influence the combined risk of physical and mental health problems in different groups within the population, for example young people versus adults, different ethnic groups and groups from different socio-economic backgrounds. To study these important questions, we propose to work together across four large UK studies in which these genetic changes have been established and which have collected rich information on physical and mental health as well as relevant risk factors. The data sets we will work with differ in the age and ethnic and socio-economic background of the participants. We will be able to follow over time how risk of physical and mental health problems influence each other and how this may be different in these different age. ethnic and socioeconomic groups. The findings will have important implications for developing better interventions for this group, for understanding complex medical risks in the population more generally and for insights into the biology of complex medical risks.

Impact of research: 
The impact will be large, as very little is yet known about the medical implication of pathogenic CNVs in the general population. Our papers have been amongst the first to document this however and have found very high risk of physical and mental health problems as well as mortality. Multimorbidity remains virtually undescribed however. There will be important implications for interventions in this population, for insights that will benefit the general population as well as for understanding the biology of multimorbidity.
Date proposal received: 
Thursday, 9 January, 2020
Date proposal approved: 
Friday, 10 January, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), A range of physical and mental health conditions, Microarrays, CNVs, PRS, physical health, mental health, cognition, risk factors

B3419 - The relationship between cognitive and neural development and a childs environment - 10/01/2020

B number: 
B3419
Principal applicant name: 
Duncan Astle | University of Cambridge (United Kingdom)
Co-applicants: 
Ms Tess Smith, Mr Tochukwu Nweze, Dr Rogier Kievit
Title of project: 
The relationship between cognitive and neural development and a child's environment
Proposal summary: 

In the UK 14 million people live in poverty. Four million of these are children. The level of child poverty is rising, and the rate is projected to accelerate in coming years. Growing up in a deprived environment can have a profoundly negative effect on a child’s development. Children from deprived backgrounds are more likely to be placed in special education, fail courses, and complete fewer years of schooling. But the adversities children encounter extend well beyond economic hardship and incorporate multiple familial factors like chaotic home life, poor parental mental and physical health, lack of community support, poor schooling and communication difficulties. These factors have a well-documented impact on multiple child outcomes including educational attainment, mental health, and behaviour. This is a global problem. Up to 50% of children and adolescents growing up worldwide experience at least one episode of childhood adversity in early life: 30% of all mental health problems are attributable to such adversity. The effects are also persistent – early adversity can set a life-long trajectory associated with poor physical and mental well-being and significantly worse occupational and economic outcomes. This results in an inter-generational cycle of disadvantage where deprivation impacts each subsequent generation. Supporting young people who face adversity is one of the major modern challenges for educators, practitioners and policy-makers, as they work to reduce educational under-attainment, poor economic outcomes and address the burgeoning mental health crisis.

Yet not all children who face adversity go on to experience poor outcomes: certain factors appear to insulate children from hardship, such that they demonstrate resilience (broadly defined as succeeding in a particular domain, such as education, despite experiencing adversity). Resilience within mental health is an increasingly recognised phenomenon, but our knowledge about which factors foster resilience across a broader range of outcomes, different populations and in response to diverse sources of adversity is currently limited. Understanding the cross-domain factors that promote resilience is vital to drive the development of interventions that improve the outcomes of child and adolescent victims of adversity. This is the purpose of our project. We want to explore how different environmental factors interact with cognitive and brain development, whether particular features of a child's environment are most strongly linked with these outcomes, and whether some factors foster resilience.

Impact of research: 
The research will benefit national policy-makers, practitioners working in educational and clinical practice, those responsible for child welfare in other institutions, and ultimately children and families who are at risk.
Date proposal received: 
Tuesday, 7 January, 2020
Date proposal approved: 
Friday, 10 January, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Cognitive impairment, Statistical methods, Development

B3437 - Examining the association between alcohol use cognitive functioning and self-harm - 10/01/2020

B number: 
B3437
Principal applicant name: 
Liam Mahedy | University of Bristol
Co-applicants: 
Prof. Marcus Munafo, Miss Daisy Drummond, Miss Kajal Shah, Miss Maddy Cooper
Title of project: 
Examining the association between alcohol use, cognitive functioning and self-harm
Proposal summary: 

Alcohol use during adolescence is a major public health concern, in particular because the brain is still developing and undergoing considerable structural and functional changes. Identifying risk factors that influence adolescent alcohol use is important to appropriately target prevention programs. One area of research that has received considerable attention is the role cognitive functioning (e.g., working memory and inhibition) play as risk for involvement in adolescent alcohol use. There is also a large literature showing a relationship between substance use and self-harm. It is possible that alcohol may increase the risk of self-harm by lowering inhibitions and impairing working memory, which is central to decision making. There is also evidence to suggest that there may be a bi-directional relationship, as several longitudinal studies have reported an association between adolescent self-harm and alcohol problems in adulthood. Although previous prospective studies have examined this association, they are often limited by the use of small sample size, different alcohol use phenotype (i.e. bingeing vs frequency), different follow-up periods, or lack of control for relevant confounders.

Impact of research: 
This research project has the potential to inform the development of cognitive training as intervention/prevention strategies aimed at reducing alcohol initiation and self-harm.
Date proposal received: 
Wednesday, 8 January, 2020
Date proposal approved: 
Friday, 10 January, 2020
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Mental health, Statistical methods, Cognition - cognitive function, Statistical methods, Alcohol use, self-harm

B3436 - Mapping the shared genetic architecture of human blood multi-omics phenotypes at cardiovascular disease risk loci - 08/01/2020

B number: 
B3436
Principal applicant name: 
Josine Min | MRC Integrative Epidemiology Unit (IEU)
Co-applicants: 
Prof Tom Gaunt, Caroline Relton, Mahsa Sheikhali Babaei
Title of project: 
Mapping the shared genetic architecture of human blood multi-omics phenotypes at cardiovascular disease risk loci
Proposal summary: 

The majority of the disease risk variants identified by genome wide association studies (GWAS) fall inside of non-coding regions, leading to the conclusion that their effects are likely to be mediated by regulation of gene expression or other molecular phenotypes. This highlights the value of utilizing multiple molecular phenotype QTLs (collectively, xQTLs) to establish the link between the regulatory genetic variant (risk allele) and various traits and diseases. In this study we will employ DNA methylation QTL, expression QTL, histone QTL, protein QTL and metabolite QTL data from peripheral blood to map shared genetic influences on multiple intermediate molecular traits in GWAS and EWAS associated loci and investigate the molecular pathways in which they play a role.

Impact of research: 
Date proposal received: 
Monday, 6 January, 2020
Date proposal approved: 
Wednesday, 8 January, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B3435 - Sex differences in the association of socioeconomic position with cardiovascular health across the life course - 08/01/2020

B number: 
B3435
Principal applicant name: 
Linda O'Keeffe | School of Public Health, University College Cork (UK)
Co-applicants: 
Minhal Ahmed
Title of project: 
Sex differences in the association of socioeconomic position with cardiovascular health across the life course
Proposal summary: 

Socioeconomic differences in cardiovascular health are evident in adulthood. When these inequalities emerge and how they change through the life course is not well understood. Understanding when inequalities in cardiovascular health emerge may inform early life prevention opportunities.

Impact of research: 
This research will provide aetiological understanding on sex differences in cardiovascular health.
Date proposal received: 
Thursday, 2 January, 2020
Date proposal approved: 
Monday, 6 January, 2020
Keywords: 
Epidemiology, Cardiovascular, Statistical methods, Cardiovascular

B3434 - Methylation of the glucocorticoid receptor gene in the development of child psychopathology - 10/02/2020

B number: 
B3434
Principal applicant name: 
Moniek Zeegers | Research Institute of Child Development and Education (Netherlands)
Co-applicants: 
Prof. Geertjan Overbeek
Title of project: 
Methylation of the glucocorticoid receptor gene in the development of child psychopathology
Proposal summary: 
Impact of research: 
Findings from this study will lead to a better understanding of family-system influences on the development of stress-related mental health disorders. Specifically, with this study we will be able—as a first research team worldwide—to identify whether parenting can prospectively predict methylation changes in the glucocorticoid system, and through these changes affect children’s likelihood of developing psychopathology.
Date proposal received: 
Wednesday, 18 December, 2019
Date proposal approved: 
Friday, 20 December, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Parenting

B3431 - Association of Maternal education with DNA-methylation - 16/12/2019

B number: 
B3431
Principal applicant name: 
Giulia Mancano | IEU
Co-applicants: 
Dr Gemma Sharp
Title of project: 
Association of Maternal education with DNA-methylation
Proposal summary: 

Maternal education, a predictor of social-economic status, has been associated with several offspring health outcomes during the life course (e.g. obesity, type 2 diabetes, cognitive function...). The biological mechanisms regulating this association are yet to be understood. Possible mediation in the maternal education-offspring health outcome relationship might be played by DNA-methylation epigenetics markers. We therefore aim to investigate how epigenetics changes are associated to maternal educational attainment.

Impact of research: 
Produce evidence in support or against the association between DNA-methylation and maternal education
Date proposal received: 
Thursday, 12 December, 2019
Date proposal approved: 
Monday, 16 December, 2019
Keywords: 
Epigenetics, Microarrays, Maternal educational attainment

B3427 - The effect of historic digit sucking on facial shape at 15 years of age - 16/12/2019

B number: 
B3427
Principal applicant name: 
Stephen Richmond | Cardiff University (UK)
Co-applicants: 
Rashed Alrashed, Dr Renata Medeiros Mirra, Dr Damian Farnell, Dr Alexei Zhurov
Title of project: 
The effect of historic digit sucking on facial shape at 15 years of age.
Proposal summary: 

A previous study in 350 6-year-old children has suggested that digit sucking has no effect on craniofacial parameters but may affect occlusal development. It is reasonable to expect that if digit sucking has an effect on the dentition this also should also influence facial shape. We have a large sample and we should be able to determine whether the frequency of digit sucking and hand used have and long-lasting changes in face shape.
1. Campos MPMS, Valença PAM, Silva GMD, Lima MC, Jamelli SR, Góes
PSA. Influence of head and linear growth on the development of malocclusion at six years of age: a cohort study. Braz Oral Res. 2018 Oct 11;32:e98.

Impact of research: 
Very little data has been explored on digit sucking in a large cohort.
Date proposal received: 
Tuesday, 10 December, 2019
Date proposal approved: 
Monday, 16 December, 2019
Keywords: 
Anthropology, Facial shape and habits, Face shape, Face - face shape

B3429 - Obesity and Inflammation - 16/12/2019

B number: 
B3429
Principal applicant name: 
Komal Satti | Dartmouth-Hitchcock medical center, New Hampshire USA (United States of America)
Co-applicants: 
Title of project: 
Obesity and Inflammation
Proposal summary: 

Between 2015 and 2016, obesity affected approximately 13.7 million children and adolescents in the United States. Children with obesity are more likely to have high blood pressure, abnormal lipids and insulin resistance even though overt cardiovascular disease may not develop for decades.Additionally, children with obesity are at increased risk for musculoskeletal and mental health disorders, as well as certain cancers. This project aims to to better understand the development and progression of the metabolic derangement seen with obesity in children as well as the associations with development of comorbidities. Inflammation is considered to be the common link between obesity and its progression to various comorbidities. If we are able to identify an early signal in children with obesity who are more likely to develop diseases such as asthma, cardiovascular disease and cancers we will be able to address the problem in a timely fashion and offer focused intervention and treatment to these high risk children

Impact of research: 
The findings from the proposed study will help lay a solid foundation for future proposed work in the use of metabolic markers to identify and prevent childhood obesity-related diseases. At the successful completion of this project we expect to have gained useful insights into the underlying mechanisms and trends of obesity leading to its end outcomes.
Date proposal received: 
Tuesday, 10 December, 2019
Date proposal approved: 
Monday, 16 December, 2019
Keywords: 
Clinical research/clinical practice, Obesity, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Breast feeding, Cardiovascular, Growth, Nutrition - breast feeding, diet, Physical - activity, fitness, function

B3432 - Hypothesis-free and pQTL analysis of deep vein thrombosis aetiology a Mendelian randomization study - 16/12/2019

B number: 
B3432
Principal applicant name: 
Emma Vincent | University of Bristol (UK)
Co-applicants: 
Andrei-Emil Constantinescu, Caroline Bull
Title of project: 
Hypothesis-free and pQTL analysis of deep vein thrombosis aetiology: a Mendelian randomization study
Proposal summary: 

Deep vein thrombosis (DVT) usually presents as a blood clot which forms in the deep veins of the legs. It can be a life-threatening disease if not identified in time, leading to pulmonary embolism or heart failure. While research have found some risk factors using observational epidemiological studies, little is known about the exact causes of DVT.

Impact of research: 
The likely output of this research will be a publication, contributing to the field of deep vein thrombosis research (DVT). We hope to strengthen evidence for suggested risk factors and to identify novel ones. We hope our study would therefore lead to the advancement of the knowledge of the field and might influence future clinical applications for DVT.
Date proposal received: 
Friday, 13 December, 2019
Date proposal approved: 
Monday, 16 December, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Obesity, Deep vein thrombosis, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cardiovascular, Genetic epidemiology, Mendelian randomisation

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.

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