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.

Click here to export results in Word format.

B3316 - Genetics susceptibility to high BMI and its relationship to food intake in children - 23/05/2019

B number: 
B3316
Principal applicant name: 
Laura Johnson | Centre for Exercise, Nutrition and Health Sciences, School for Policy Studies, University of Bristol (United Kingdom)
Co-applicants: 
Franscisca Ibacache
Title of project: 
Genetics susceptibility to high BMI and its relationship to food intake in children.
Proposal summary: 
Impact of research: 
Understand the extent of genetics influence in relation to the development of obesity in children, and consequently, leading to stratified approaches to prevention and treatment, which is crucial for dealing with the current obesity epidemic that is known to have a multi-factorial aetiology.
Date proposal received: 
Monday, 20 May, 2019
Date proposal approved: 
Thursday, 23 May, 2019
Keywords: 
Genetics, Obesity, Statistical methods, Genetics

B3318 - Genetics of Child Growth Trajectories - 23/05/2019

B number: 
B3318
Principal applicant name: 
Kateryna D. Makova | Penn State University Department of Biology (United States)
Co-applicants: 
Sarah JC Craig, PhD, Francesca Chiaromonte, PhD, Matthew L. Reimherr, PhD, Ana Kenney
Title of project: 
Genetics of Child Growth Trajectories
Proposal summary: 

Our team is interested in variables that influence the weight gain patterns of young children. In this study we aim at identifying genetic variants (differences in the DNA between individuals) that could be used to predict which children are most at risk at developing childhood obesity. With this information we could identify children who would benefit most from early life obesity interventions.

Impact of research: 
Childhood obesity is a growing epidemic. With early life interventions, this growth could be prevented or even reversed. However, these interventions can often be expensive and labor intensive, which precludes their widespread implementation. If a test (such as a PRS) could be performed that identifies children who are most at risk of developing childhood obesity, intervention efforts could be focused on that sub-population. This would decrease the burden of intensive intervention programs.
Date proposal received: 
Tuesday, 21 May, 2019
Date proposal approved: 
Thursday, 23 May, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Obesity, GWAS, Statistical methods, Birth outcomes, BMI, Childhood - childcare, childhood adversity, Genetic epidemiology, Genetics, Genomics, Growth, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods

B3314 - The metabolomic profiling of cigarette smoking - 20/05/2019

B number: 
B3314
Principal applicant name: 
Osama Mahmoud | School of Psychological Science and Integrative Epidemiology Unit (IEU), University of Bristol (United Kingdom)
Co-applicants: 
Prof. Marcus Munafo , Professor George Davey Smith
Title of project: 
The metabolomic profiling of cigarette smoking
Proposal summary: 

It is hypothesized that exposure to cigarette smoking could influence the risk of cardiovascular diseases through direct modification of the lipoprotein profile, lipotoxicity and change in chronic oxidative stress. However, the metabolic profiling of cigarette smoking have not been precisely investigated.
Using the ALSPAC data, this study aims to provide insights into the molecular effect of smoking both in terms of the composition and the concentration of the molecular species affected.

Impact of research: 
Assuming that our hypothesis is true, this study will provide novel insights into the metabolic profiling of cigarette smoking in early adulthood. This work thus has the potential to contribute to the growing body of evidence suggesting association of smoking with cardiovascular disease through modification of metabolomics. Of particular interest will be whether we can identify potential mechanisms that are linking smoking exposure to cardiovascular disease.
Date proposal received: 
Thursday, 16 May, 2019
Date proposal approved: 
Monday, 20 May, 2019
Keywords: 
Epidemiology, coronary heart disease and cardiovascular disease., Metabolomics, NMR, Statistical methods, Cardiovascular, Metabolic - metabolism, cigarette smoking

B3315 - Intergeneration transmission of sexual abuse and violence - 20/05/2019

B number: 
B3315
Principal applicant name: 
Kate Walker | Coventry University, Coventry University (UK)
Co-applicants: 
Prof Sarah Brown
Title of project: 
Intergeneration transmission of sexual abuse and violence
Proposal summary: 

Children, particularly daughters, of mothers who have been victims of sexual violence and abuse have a higher risk of becoming victims of sexual violence and abuse, compared to children of mothers who have no such victimisation histories. The majority of studies examining this intergeneration 'transmission' of sexual abuse and violence have been conducted using samples from populations in which there are a high number of victims and outside the UK. Furthermore, studies have tended to focus on the sexual abuse histories of the mother and not the father. This study, using a general population sample (i.e., of people not specifically identified on the basis of being victims of sexual abuse) will enable us to identify the extent to which mothers' sexual abuse experiences increase the risk of similar victimisation in their children. We will also examine the impact of the sexual histories of fathers and what other factors (e.g., other types of abuse experienced by the mother and/or father, parents' mental health, children's early development and conduct disorders) exacerbate or reduce the risk of intergeneration transmission.

Impact of research: 
This research is important to understand in a general UK population study whether the child of parents who have been sexually abuse are at a greater risk of being victims of sexual abuse than children whose parents have not been abused. It will also highlight whether it is the sexual victimisation specifically or other factors that co-occur that increase the risk. This will have important implications for the prevention of sexual abuse, particularly in respect of identifying areas that can be the focus of intervention and support for parents who have experienced sexual abuse, in order that the risk to their children is minimised. If the findings show that the children of sexually abused parents are not at increased risk (i.e., due to the nature of the sample in this study compared to the specific sexual abuse population samples in most other studies), then the findings have significant impact for theory/policy developed on the belief of intergenerational transmission.
Date proposal received: 
Saturday, 18 May, 2019
Date proposal approved: 
Monday, 20 May, 2019
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Child sexual abuse Inter-generation transmission Sexual violence and abuse

B3310 - Puberty timing and cardiovascular structure and function at age 25 years - 13/05/2019

B number: 
B3310
Principal applicant name: 
Linda O'Keeffe | MRC Integrative Epidemiology Unit, University of Bristol (UK)
Co-applicants: 
Lisa Ryan
Title of project: 
Puberty timing and cardiovascular structure and function at age 25 years
Proposal summary: 

Puberty timing has been decreasing for several decades. Earlier puberty is thought to be associated with greater cardiovascular disease risk. The aim of this project is to examine the association between puberty timing and cardiac measures at age 25 years.

Impact of research: 
This work will help to clarify the evidence around puberty timing and its health effects in a contemporary birth cohort with rich data. Impacts may include implications for initiatives to prevent early puberty due to its downstream cardiovascular impacts.
Date proposal received: 
Thursday, 9 May, 2019
Date proposal approved: 
Monday, 13 May, 2019
Keywords: 
Epidemiology, Puberty timing; cardiovascular disease, Statistical methods, Offspring

B3309 - Understanding the mechanisms linking the urban environment to psychotic experiences across the lifespan - 21/05/2019

B number: 
B3309
Principal applicant name: 
Joanne Newbury | King's College London and University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
Understanding the mechanisms linking the urban environment to psychotic experiences across the lifespan
Proposal summary: 

Individuals who are raised in urban (versus rural) settings are around twice as likely to develop a psychotic disorder in adulthood. This association has now been replicated for subclinical psychotic experiences during childhood and adulthood (e.g., hearing voices, extreme paranoia). These symptoms lie on a continuum with clinical psychosis and therefore provide a useful marker to explore the urbanicity-psychosis association in the general population. Given that 70% of the world’s population will live in urban areas by 2050, it is essential that we uncover the pathways linking cities and psychosis so that we can inform intervention efforts.

Research supports a role of neighbourhood social factors correlated with urbanicity in the aetiology of psychotic experiences, such as neighbourhood disorder and social fragmentation (i.e., weak connections between individuals in a community). In addition, emerging research suggests that urban residents have a higher genetic risk for schizophrenia, meaning that the urbanicity-psychosis association could be partly confounded by genes.

However, very little is currently known about the potential role of air pollution in the link between cities and psychosis. Air pollution is the world's biggest environmental health problem, and is particularly problematic in cities. Recent cross-sectional research has provided the first evidence linking air pollution to psychotic experiences among teenagers.

However, longitudinal research into the link between air pollution and psychotic experiences is needed to establish the temporal nature of associations. In addition, neighbourhood social exposures are highly correlated with air pollution (i.e., the most deprived neighbourhoods also tend to be the most polluted). The interplay between neighbourhood social conditions and air pollution (i.e., confounding versus interaction) in relation to psychotic experiences is not known. Furthermore, though influences on inflammatory and cognitive processes are the most commonly suggested mechanisms linking urban exposures to psychosis, very few studies have directly tested these mechanisms.

This project will examine 1) the longitudinal associations of air pollution exposure from birth to age 15 with psychotic experiences in childhood and adolescence, 2) the interplay between neighbourhood social characteristics (neighbourhood disorder and social fragmentation) and air pollution in the emergence of psychotic experiences, and 3) potential biopsychological mechanisms linking urban neighbourhood exposures with psychotic experiences, including inflammation and cognition.

Impact of research: 
This research will serve a range of stakeholders, including researchers, industry, policymakers, and the general public. Air pollution is a known cause of physical disease, but very little is known about the impact of air pollution on mental health problems. My research will contribute to the evidence base on air pollution and mental health, which is essential for policymakers to make the economic case for tightening air pollution restrictions. Though a major global challenge, urban expansion nevertheless provides a unique opportunity for promoting healthy urban design. My research will also be useful to industry and policymakers to provide evidence on targets in the urban environment that could be modified to improve mental health. By identifying modifiable targets in the urban environment, this research has the strong potential to improve the mental health of urban residents now and for years to come. My plan for maximising impact of the findings is as follows: 1) I expect that the research proposed will lead directly to at least four publications in highly regarded journals with a broad readership. 2) I will disseminate findings via oral presentations at six international psychiatry/epidemiology conferences that attract a wide audience such as MQ Mental Health Science Meeting. 3) I will liaise with press teams such as the Science Media Centre to maximise the impact of the findings through press releases and press briefings. 4) I will ensure that findings are clearly presented to the public by preparing blogs and podcasts, and by participating in interactive open workshops and talks. 5) I will share my findings with policymakers by holding a policy lab with support from Policy Bristol.
Date proposal received: 
Wednesday, 8 May, 2019
Date proposal approved: 
Thursday, 9 May, 2019
Keywords: 
Epidemiology, Mental health, Statistical methods, Environment - enviromental exposure, pollution

B3306 - Modelling techniques for accelerated longitudinal studies - 07/05/2019

B number: 
B3306
Principal applicant name: 
Gwen Fernandes | Population Health Sciences (United Kingdom)
Co-applicants: 
Dr Jon Heron, Dr Fanny Kilpi , Professor Kate Tilling, Professor Debbie Lawlor
Title of project: 
Modelling techniques for accelerated longitudinal studies
Proposal summary: 

I met with Dr Fanny Kilpi following her presentation on some of the maternal data with cognitive outcomes from ALSPAC. Dr Jon Heron noticed the similarity in terms of structure of her dataset and wondered whether we could use these data to trial a new method of handling data produced from another study that we are involved with called cVEDA.

The purpose of this exercise is to trial a method/s of dealing with data including missing data that is completely new to me and the cVEDA (Indian cohort) team. It is purely for learning purposes and to consider any assumptions and adjustments we may make to our models when our final dataset is officially released at the end of 2020 i.e. a practice dataset.

Despite a publishable manuscript not being our primary goal it would be useful to have some input into how best to use these data, and which exclusions to make (e.g. HRT etc). Also, we may discover the analytical approach to be useful to you and then a publication may result if all collaborators consider this a worthwhile exercise and outcome.

Impact of research: 
The most tangible impact of this work will be to help guide our analysis plans for the final cVEDA dataset. As this is exploratory, we do not envisage publishing any of our findings but we will share these with Dr Kilpi and her team at every stage to ensure that we have their statistical input but also, if it might help inform their results, the collaboration could be mutually helpful.
Date proposal received: 
Wednesday, 1 May, 2019
Date proposal approved: 
Tuesday, 7 May, 2019
Keywords: 
Epidemiology, Methodological development without focus on specific outcome however we will be using either grip strength (biomechanical outcome) or cognitive functioning (mental health outcome) , Computer simulations/modelling/algorithms, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3307 - A multi-cohort GWAS of income using ALSPAC - 07/05/2019

B number: 
B3307
Principal applicant name: 
Tim Morris | University of Bristol (United Kingdom)
Co-applicants: 
Prof Nic Timpson, Dr Neil Davies, Mr Alex Kwong
Title of project: 
A multi-cohort GWAS of income using ALSPAC
Proposal summary: 
Impact of research: 
Academic
Date proposal received: 
Thursday, 2 May, 2019
Date proposal approved: 
Tuesday, 7 May, 2019
Keywords: 
Genetics, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., GWAS, Genetics, Genome wide association study, Social science

B3308 - The development of genetically-based pathways underlying problematic alcohol use - 07/05/2019

B number: 
B3308
Principal applicant name: 
Frances Wang | University of Pittsburgh (United States)
Co-applicants: 
Bernie Devlin
Title of project: 
The development of genetically-based pathways underlying problematic alcohol use
Proposal summary: 

Problematic alcohol use is a serious public health threat. Research suggests that there exist unique, biologically-based "types" of adolescents who are at high risk for problematic alcohol use. Discovering these types will help us identify personalized prevention targets for this condition. This proposal will examine patterns by which adolescent risk factors for problematic alcohol use (conduct problems, depressive symptoms, and personality traits) are inherited to identify new highly heritable traits. This proposal will also test sex differences in these new genetically-based traits and their relation to problematic alcohol use to shed light on whether differing treatments are needed for males and females.

Impact of research: 
This research could accelerate personalized prevention targets relevant to problematic alcohol use.
Date proposal received: 
Thursday, 2 May, 2019
Date proposal approved: 
Tuesday, 7 May, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, GWAS, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Development, Genetics, Psychology - personality, Sex differences

B3297 - Methods to identifying genetically regulated components using transcriptome data - 09/05/2019

B number: 
B3297
Principal applicant name: 
Jin Liu | Duke-NUS Medical School, National University of Singapore (Singapore)
Co-applicants: 
Title of project: 
Methods to identifying genetically regulated components using transcriptome data
Proposal summary: 

Although genome-wide association studies (GWAS) have been very successful in identification of genetic variants associated with complex traits, the mechanistic links between these variants and complex traits are still largely unknown. A scientific hypothesis is that genetic variants influence complex traits via affecting cellular traits, e.g., regulating gene expression and altering protein abundance. Yet, how to systematically examine this hypothesis remains an open problem.
Recently, large genomic consortia are generating a vast volume of genomic data towards comprehensively characterizing the regulatory role of genetic variants. For example, the Genotype-Tissue Expression Project (GTEx) has collected genomic profile of 449 individuals, comprised of measurements of gene expression from multiple tissues and about 12.5 million DNA bases, providing unprecedented opportunities to dissect genetic contributions to complex traits. Statistical methods that effectively harness multilayer data (genetic variants, cellular traits and organismal traits) for mechanistic interpretation are highly demanding. The phenomenon that genetic variants have individually weak effects on complex traits makes statistical modeling very challenging, because it requires that the developed models can efficiently exploit information in low signal-noise-ratio (SNR) regimes.
In the proposed research, we aim at developing statistical methods to advance mechanistic understanding of the role of associated variants in complex traits. The key idea is built upon the emerging scientific evidence that genetic effects at the cellular level are much stronger than those at the organismal level. In our pilot study, we proposed a statistical approach, AUDIS, to accounting for uncertainty in dissecting genetic contributions to complex traits by leveraging regulatory information. We also developed a parameter expanded expectation-maximization (PX-EM) algorithm to ensure that AUDIS can perform stably in low SNR regimes. Interestingly, two popular methods in this field, SKAT and PrediXcan can be connected via a stagewise view of AUDIS, as supported by results from comprehensive simulation studies. Then we applied stagewise AUDIS to analyze 20 complex traits in GERA by incorporating the transcriptome data in the Genetic European Variation in Health and Disease (GEUVADIS) Project. Real data analysis results show that AUDIS can identify more genetically regulated genes that are significantly associated with complex traits, without inflated type I errors. To continue in this promising direction, we propose generalized AUDIS models to allow detection of trait-associated expression quantitative trait loci (eQTLs), as well as integrative analysis of GWAS data with transcriptome data from multiple tissues. We also propose to investigate theoretical properties of our methods, e.g., why AUDIS can be immune to model mis-specification.
The novelty of this research is that a statistically efficient and computationally feasible framework is developed to dissect genetic contributions to complex traits. Specifically, the proposed methods (AUDIS and its generalizations) can effectively borrow regulatory information at the cellular level and then boost statistical power of identifying genetically-regulated and trait-associated genes, even though in low SNR regimes. The stagewise view of AUDIS not only offers a statistical connection between existing approaches, but also highlights the importance of statistically rigorous design. Unlike conventional engineering approaches that often only consider a point estimate or a maximum a posteriori probability estimate, the stagewise view of AUDIS implies that the posterior distribution obtained in former stage should be naturally incorporated as the prior in the later stage. This gives birth to a modularized design of the whole data analytics system, greatly helping biomedical researchers to gain new scientific insights. The statistical and computational skills developed here are also broadly useful to many other applications in the field of data science.

Impact of research: 
The impact of our research will lie on two sides. First, we will develop statistically rigorous methods to conduct integrative analysis of multi-platform genetic/genomic data. Second, the results from our analysis will help people better understand the mechanistic link that genetic variants influence complex traits via affecting cellular traits.
Date proposal received: 
Tuesday, 16 April, 2019
Date proposal approved: 
Tuesday, 30 April, 2019
Keywords: 
Bioinformatics, Bone disorders - arthritis, osteoporosis, Developmental disorders - autism, Cancer, Diabetes, Eating disorders - anorexia, bulimia, Eczema, Hypertension, Mental health, Obesity, Computer simulations/modelling/algorithms, GWAS, Medical imaging, Statistical methods, Statistical methods

B3299 - Clinical and Genetic Predictors of Polycystic Ovary Syndrome - 30/04/2019

B number: 
B3299
Principal applicant name: 
Laura Torchen | Northwestern University Feinberg School of Medicine (USA)
Co-applicants: 
Laura Rasmussen-Torvik, Margrit Urbanek
Title of project: 
Clinical and Genetic Predictors of Polycystic Ovary Syndrome
Proposal summary: 

Polycystic ovary syndrome (PCOS) is a common disorder affecting women associated with major adverse health outcomes including subfertility and increased risk for type 2 diabetes. PCOS is a complex genetic trait which arises from a combination of genetic risk and environmental such as obesity. Currently, a conclusive diagnosis of PCOS cannot be made until sexual maturation is complete and the patient develops the characteristic diagnostic features of hyperandrogenism, oligomenorrhea, and/or polycystic ovarian morphology. However, studies in girls with increased risk for PCOS, including daughters of affected women and girls with obesity, have identified early reproductive and metabolic features of the syndrome even prior to the onset of puberty. Investigations into the early origins of PCOS have been limited by small sample size and lack of longitudinal data. The ALSPAC cohort includes critical data needed to investigate PCOS, including maternal reproductive histories, hormone levels, and offspring pubertal development, reproductive hormone levels, and menstrual histories. These proposal seeks to identify early clinical and genetic predictors of PCOS. Data collected in this project will be used for preliminary data in planned future innovative investigations of the early origins of PCOS. This study will propose using a translational approach integrating whole genome sequencing, epigenetic, and metabolomics data available in this cohort with clinical predictors of PCOS. This proposed research will have a sustained and lasting impact on the field as it will inform future efforts toward development of targeted prevention and early treatment approaches in at-risk girls.

Impact of research: 
The proposed research will generate critical preliminary data required for a planned future extramural application aiming to employ this rich data source for innovative investigations of the early origins of PCOS. This study will propose using a translational approach integrating whole genome sequencing, epigenetic, and metabolomics data available in this cohort with clinical predictors of PCOS. This proposed research will have a sustained and lasting impact on the field as it will inform future efforts toward development of targeted prevention and early treatment approaches in at-risk girls.
Date proposal received: 
Wednesday, 17 April, 2019
Date proposal approved: 
Tuesday, 30 April, 2019
Keywords: 
Endocrinology, Polycystic ovary syndrome, GWAS, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Puberty, BMI, Development, Genetics, Genome wide association study, Hormones - cortisol, IGF, thyroid, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism, Offspring

B3305 - EFSA systematic review of Sugars 30-04-2019 - 120653 - 30/04/2019

B number: 
B3305
Principal applicant name: 
Pauline Emmett | CACH, University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
EFSA systematic review of Sugars (30-04-2019 - 12:06:53)
Proposal summary: 

Review of the literature relating dietary intake of sugars to adverse health outcomes is being undertaken by EFSA. Five ALSPAC papers have been selected for the review and need extra details added on precise intakes of sugars in order to improve their usefulness to the review

Impact of research: 
To enhance the contribution of ALSPAC to a systematic review
Date proposal received: 
Tuesday, 30 April, 2019
Date proposal approved: 
Tuesday, 30 April, 2019
Keywords: 
Epidemiology, Diabetes, BMI

B3304 - HDR Data Discovery Preparation for ATLAS - 02/05/2019

B number: 
B3304
Principal applicant name: 
Philip Quinlan | University of Nottingham (UK)
Co-applicants: 
Matt Styles, Tom Giles
Title of project: 
HDR Data Discovery: Preparation for ATLAS
Proposal summary: 

Medical research in the UK is still hindered by a perceived lack of suitable data and sample resources that can be used by the research community. This perception contrasts starkly with the knowledge that there are hundreds of potential resources that can supply data and samples. The work of the Tissue Directory and Coordination Centre and backed by the Medicines Discovery Catapult has shown that the actual problem experienced by both academic and commercial researchers is the inability to find suitable resources. The consequence is that researchers tend to utilise the resources that are close by proximity (because they can go and talk to the resource directly) rather than close to their research goals. This approach is driven because there is no easy mechanism in which to discover other potential national resources.
The Tissue Directory and Coordination Centre (TDCC) is the UKs national centre that is tasked with coordinating biobanks (samples and data) to ensure that researchers re-use existing resources before seeking to collect new samples or datasets. TDCC is a joint endeavour between the University of Nottingham and University College London. TDCC has created a Tissue Directory to allow a high-level search on aggregated meta data that works well for clinical and disease orientated biobanks. In part the Tissue Directory has begun to solve the issue of findability but the challenge has evolved. Researchers can search on very high-level classification of disease, gender and age and resources matching those criteria are displayed. This Directory acts as a first filter but does not allow researchers to ask detailed feasibility questions. Although candidate resources are listed the confidence that the data or samples required do actually exist remain low once sub-typing is considered. Assuming the identified resources have a search portal (many do not), the researcher would have to create accounts in each in order to perform a more detailed search. This effort can often go unrewarded as the ultimate answer is often that once more detailed criteria are added, the resource does not have the data or samples required.

It is clear that in order to support and utilise existing UK investment in health care resources we must have a more efficient mechanism in which a researcher can ask a relatively detailed question and understand whether resources exist that could support them. It is especially important that researchers find out quickly if something is not feasible (rather than investing time and finding it is not) and equally that referrals to the resources (such as ALSPAC) from the search system does not create irrelevant traffic. By bringing together key academic, technology and research infrastructure stakeholders we are seeking to change this to make the necessary change.

Impact of research: 
Date proposal received: 
Monday, 29 April, 2019
Date proposal approved: 
Tuesday, 30 April, 2019
Keywords: 
Data Discovery at scale

B3302 - Road traffic injuries and risk behaviours in children and young people with special educational needs - 29/04/2019

B number: 
B3302
Principal applicant name: 
Julie Mytton | University of the West of England, Bristol
Co-applicants: 
Dr Nicola Christie, Sarah O'Toole, Dr Elizabeth Orton, Prof Alan Emond
Title of project: 
Road traffic injuries and risk behaviours in children and young people with special educational needs
Proposal summary: 

Road traffic injuries are known to affect the vulnerable in our society. Children travelling to and from school, and young people especially young road drivers, are known to be at risk of being involved in a road traffic crash. We wish to explore whether children and young people with special educational needs (including physical or behavioural disabilities or learning difficulties) are at an increased risk of being injured in a road traffic crash. By better understanding how children with special educational needs are involved in road traffic crash events we can develop and test targeted interventions to prevent these injuries and deaths, and support the parents and carers of children and young people with special educational needs.

Impact of research: 
The identification of vulnerable road users and associated risk factors for injury may inform policy and prevention / intervention efforts to reduce road traffic injuries. Understanding how the risk of road traffic injury compares in children with SEND to those in typically developing young people may inform efforts to support these young people to keep safe on the roads. The parents and carers of young people with SEND may be more involved in providing support to their children beyond the time period of young people without such needs. The outputs from this research may therefore inform parents and carers of any additional risk their child may face and lead to improved resources for parents and carers. We intend to distribute outputs from this research to networks of organisations working with young people with SEND. Outputs will also include peer reviewed publications and conference presentations.
Date proposal received: 
Saturday, 20 April, 2019
Date proposal approved: 
Monday, 29 April, 2019
Keywords: 
Epidemiology, Injury, Statistical methods, Injury (including accidents)

B3303 - An integrative analysis of biological and environmental risks for mental ill-health in young adulthood to precision psychiatry - 02/05/2019

B number: 
B3303
Principal applicant name: 
David Cotter | Royal College of Surgeons in Ireland (ireland)
Co-applicants: 
Stan Zammit, Mary Cannon , Gerard Cagney , Lorraine Brennan, Dr David Mongan, Colm Healy
Title of project: 
An integrative analysis of biological and environmental risks for mental ill-health in young adulthood – to precision psychiatry
Proposal summary: 

Childhood adversity is associated with increased risk of future psychiatric illness (Croft et al., 2018). Raised levels of markers of inflammation are also associated future psychiatric illness. We have shown that certain lipids (O'Gorman et al,2017 ) and complement and coagulation proteins (English et al, 2018; Focking et al, 2019) are also raised and /or dysregulated in association with future psychotic illness, and we have shown that these lipid and proteins changes are functionally related to each other (Madrid et al, 2019). Changes to these biological markers may reflect these environmental exposures, in addition to representing novel targets for therapeutic intervention. We have also shown that the complement and coagulation pathway proteins are elevated by exposure to stress in an animal model of social defeat (Focking et al, 2019). There are however, important gaps in our knowledge regarding the relationship between psychiatric outcomes, early exposure to adversity, and early biological measures such as blood protein, lipid, and inflammatory markers levels. Our proposal will address these gaps.

This current proposal aims to utilise a longitudinal design involving all subjects within the ALSPAC Cohort who gave blood at age 11 (n=2160) and / or age 17 (n=1776) and who participated in interviews at age 24 . Cytokine, proteomic and lipidomic analyses will be undertaken in plasma samples from all of these subjects. Exposure to childhood adversity will be determined using existing data from ALSPAC children and parents for a range of possible experiences such as bullying, physical abuse, sexual abuse and emotional neglect, as previously described (Croft et al., 2018). The primary outcomes of interest would be subjects at age 24 who report 1) psychotic experiences 2) depressive / affective symptoms 3) anxiety symptoms and 4) fulfill criteria for any psychiatric disorder at age 24. A secondary outcome will be that of global functioning, as determined from available ALSPAC data, at age 24.

Data will be compared and integrated between groups, and examined in relation to the detailed environmental exposure data available within ALSPAC.

Our overarching aim is to investigate the longitudinal relationship between environmental exposures, blood markers and different psychiatric outcomes.

We have the following specific objectives;
1. To investigate the longitudinal pattern of biomarker change in the different disorders.
2. To investigate the relationship between environmental exposures and biomarker expression.
3. To integrate this data with other, already available, genomic, neuroimaging and neuropsychology data in order to build a predictive model of psychiatric disorders generally based on early biological and environmental data.

This proposal represents a unique opportunity to understand the relationship between environmental experiences, longitudinal measures of biological markers and psychiatric outcomes at age 24.

References:

Croft, J., Heron, J., Teufel, C., Cannon, M., Wolke, D., Thompson, A., . . . Zammit, S. (2018). Association of Trauma Type, Age of Exposure, and Frequency in Childhood and Adolescence With Psychotic Experiences in Early Adulthood. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.3155. Davison J, O'Gorman A, Brennan L, Cotter DR. A systematic review of metabolite biomarkers of schizophrenia. Schizophr Res. 2018 May;195:32-50. doi: 10.1016/j.schres.2017.09.021. Epub 2017 Sep 22. Review. PMID: 28947341.

Davison J, O'Gorman A, Brennan L, Cotter DR. A systematic review of metabolite biomarkers of schizophrenia. Schizophr Res. 2018 May;195:32-50. doi: 10.1016/j.schres.2017.09.021. Epub 2017 Sep 22. Review. PMID: 28947341.

English JA, Lopez LM, O'Gorman A, Föcking M, Hryniewiecka M, Scaife C, Sabherwal S, Wynne K, Dicker P, Rutten BPF, Lewis G, Zammit S, Cannon M, Cagney G, Cotter DR. Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort. Schizophr Bull. 2018 Feb 15;44(2):297-306. PMID: 29036721.

Föcking M, Sabherwal S, Cates HM, Scaife C, Dicker P, Hryniewiecka M, Wynne K, Rutten BPF, Lewis G, Cannon M, Nestler EJ, Heurich M, Cagney G, Zammit S, Cotter DR. Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress. Mol Psychiatry. 2019 Jan 11. PMID: 30635638.

Madrid-Gambin F, Föcking M, Sabherwal S, Heurich M, English JA, O'Gorman A, Suvitaival T, Ahonen L, Cannon M, Lewis G, Mattila I, Scaife C, Madden S, Hyötyläinen T, Orešič M, Zammit S, Cagney G, Cotter DR, Brennan L. Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children. Biol Psychiatry. 2019 Jan 30. PMID: 30878195.

O'Gorman A, Suvitaival T, Ahonen L, Cannon M, Zammit S, Lewis G, Roche HM, Mattila I, Hyotylainen T, Oresic M, Brennan L, Cotter DR. Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Transl Psychiatry. 2017 Sep 26;7(9):e1240. doi: 10.1038/tp.2017.211. PMID: 28949339

Impact of research: 
We will have an improved understanding of the biological and adversity related underpinnings of age 24 psychiatric disorder. We aim to be able to improve prediction of future psychiatric disorders from as early as age 11. This should allow earlier and more effective treatment of those at risk of future psychiatric disorder.
Date proposal received: 
Friday, 26 April, 2019
Date proposal approved: 
Monday, 29 April, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Mass spectrometry, Biological samples -e.g. blood, cell lines, saliva, etc.

B3293 - Exploring Illicit Drug Use in ALSPAC at age 24 comparison with general population and predictors of use - 18/04/2019

B number: 
B3293
Principal applicant name: 
Lindsey Hines | University of Bristol
Co-applicants: 
Professor Matthew Hickman, Ms Hannah Charles
Title of project: 
Exploring Illicit Drug Use in ALSPAC at age 24: comparison with general population, and predictors of use
Proposal summary: 

Substance use in young adulthood is associated with considerable morbidity, a situation which is substantially increasing, and a greater burden in young males [1]. SubstanceIllicit substance use of drugs use is taken to be illegal substances such as cannabis, cocaine, and synthetic stimulants . Use of these illegal substances is associated with an increased risks of addiction, overdose and long-term health effects, and therefore presents a significant public health concern. The link between substance use and poor mental health, educational attainment and subsequent employment is well documented [3]. Harms may be increased if use is during adolescence, a period of development is characterised by extensive cognitive and emotional development, which can be inhibited by substance use, and have a negative impact of future life outcomes [1]. A recent study suggested that in terms of brain development, adolescence should be considered up to age 25 [2]. Focussing on adolescence is important, as this is when most people start engaging in substance use, and therefore this period of life is important for the timing of preventative interventions [4]. Of interest is the substance use that persists throughout adolescence and into adulthood, which could progress to dependent use and be damaging to health.
However, there is marked global variation in prevalence of use of these substances, which indicates that contextual and individual factors influence this behaviour. As Mmuch of this data comes from self-reported questionnaires, and aspects of data collection may also affect differences in prevalence of reported use. Substance use is taken to be illegal substances such as cannabis, cocaine, and synthetic stimulants. Use of these illegal substances is associated with an increased risk of addiction, overdose and long-term health effects, and therefore presents a significant public health concern. Of interest is the substance use that persists throughout adolescence and into adulthood, which could progress to dependent use and be damaging to health. This period of adolescence is characterised by extensive cognitive and emotional development, which can be inhibited by substance use, and have a negative impact of future life outcomes [1]. A recent study suggested that in terms of brain development, adolescence should be considered up to age 25 [2]. The link between substance use and poor mental health, educational attainment and subsequent employment is well documented [3]. However, it is less clear why geographical variations in substance use occur, and the factors that predict drug use during young adulthood. Focussing on young adulthood is important as this is when most people start engaging in substance use, and therefore this period of life is important for the timing of preventative interventions [4]. To fully characterise the problem of substance use in this age group, more work is needed to understand the extent of substance use and identify risk factors that predict drug use.

Impact of research: 
Date proposal received: 
Tuesday, 9 April, 2019
Date proposal approved: 
Thursday, 18 April, 2019
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B3295 - Internalising problems in children An epigenome-wide association study - 18/04/2019

B number: 
B3295
Principal applicant name: 
Gemma Sharp | University of Bristol (United Kingdom)
Co-applicants: 
Laura Schellhas
Title of project: 
Internalising problems in children: An epigenome-wide association study
Proposal summary: 

Rationale: Internalising problems (depression & anxiety) in children have been found to be predictive of negative outcomes later in life (Sallis et al., 2018) but the biological mechanisms underlying the development of these disorders are not well understood. There is some evidence that epigenetics might play a role, but results are mixed (Barker, Walton, & Cecil, 2018). In this study, we will examine internalizing traits in childhood and methylation, both cross-sectionally and at birth.

Impact of research: 
Date proposal received: 
Thursday, 11 April, 2019
Date proposal approved: 
Thursday, 18 April, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Epigenome-wide association study, Childhood - childcare, childhood adversity, Development, Epigenetics

B3296 - Exploring the associations between autistic traits and multiple risk behaviours MRB using the ALSPAC cohort - 18/04/2019

B number: 
B3296
Principal applicant name: 
Caroline Wright | UoB PHS (United Kingdom)
Co-applicants: 
Dr Jon heron, Dr Dheeraj Rai, Amanda Ly
Title of project: 
Exploring the associations between autistic traits and multiple risk behaviours (MRB) using the ALSPAC cohort
Proposal summary: 

Previous research has shown associations between autistic traits and a higher risk of violent offending (adjusted relative risk = 1.39, 95% CI = 1.23−1.58).
Multiple risk behaviours such as smoking, alcohol consumption and antisocial behaviour are prevalent during adolescence and have also been shown to co-occur during this period. A growing body of evidence suggests that these behaviours are strongly associated, some causally, with adverse health outcomes in later life, including chronic health conditions, morbidity and premature mortality. It is therefore important to establish antecedents of MRB in order to develop effective interventions

Impact of research: 
It will contribute towards Amanda's PhD research, will be written up as a report for the Wellcome Trust, and hopefully will be written into a published paper
Date proposal received: 
Friday, 12 April, 2019
Date proposal approved: 
Thursday, 18 April, 2019
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Obesity, Cohort studies - attrition, bias, participant engagement, ethics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3294 - 2 Sample MR Lung function and Cognition - 18/04/2019

B number: 
B3294
Principal applicant name: 
Raquel Granell | IEU Population Health Sciences Bristol Medical School
Co-applicants: 
Dr James Dodd, Daniel Higbee, Prof George Dave Smith, Prof John Henderson
Title of project: 
2 Sample MR Lung function and Cognition
Proposal summary: 

Observational studies have reported associations between low lung function and dementia risk but cannot test causality of this relationship. If causal, interventions to maintain lung function with ageing could reduce the burden of dementia. It is unclear how early in life the association between low lung function and cognitive impairment begins.
Observational studies have shown an association between asthma and multi-morbidity, especially psychological e.g. anxiety and depression. However this work has been carried out on small numbers of patients, and is purely cross-sectional. Using ALSPAC data we can do larger studies longitudinally gaining insight into how early these affects appear, how long they last and how severe. If we find a consistent association then we may be able to test for causality.

Impact of research: 
Date proposal received: 
Wednesday, 10 April, 2019
Date proposal approved: 
Thursday, 18 April, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Cognitive impairment, Respiratory - asthma, Statistical methods, Mendelian Randomization, Lung function

B3298 - Dynamic Changes in DNA Methylation as a Candidate Causal Pathway Between Adolescent Cannabis Exposure and Psychosis - 18/04/2019

B number: 
B3298
Principal applicant name: 
Randi Schuster | Massachusetts General Hospital/Harvard Medical School (United States of America)
Co-applicants: 
Title of project: 
Dynamic Changes in DNA Methylation as a Candidate Causal Pathway Between Adolescent Cannabis Exposure and Psychosis
Proposal summary: 

The link between cannabis use and psychosis has been robustly documented. However, it is not known whether cannabis escalation in youth at risk for psychosis has a causal putative influence on reduced cognitive and psychiatric functioning, and whether changes in DNA methylation may mechanistically explain this association.

Impact of research: 
Early cannabis exposure has become a growing social phenomenon in our society; however, it is occurring in a population that varies with respect to its consequences. Therefore, this study will elucidate critical biological signatures of cannabis exposure in youth vulnerable to schizophrenia. A better understanding of the mechanisms underlying the link between cannabis and psychosis will improve prognosis, diagnosis, treatment and policy.
Date proposal received: 
Wednesday, 17 April, 2019
Date proposal approved: 
Thursday, 18 April, 2019
Keywords: 
Genetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, GWAS, epigenetics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Cognition - cognitive function, Epigenetics, Genetics, Genome wide association study, Psychology - personality

Pages