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.

B2800 - Are effects of early-life oxidant exposures on asthma risk modified by TRPA1 variants and mediated by TRPA1 methylation - 2016/05/12

B number: 
B2800
Principal applicant name: 
Seif Shaheen | Barts and The London School of Medicine and Dentistry, Queen Mary University of London (UK)
Co-applicants: 
John Henderson, Caroline Relton, Annabelle Bedard
Title of project: 
Are effects of early-life oxidant exposures on asthma risk modified by TRPA1 variants and mediated by TRPA1 methylation?
Proposal summary: 

In the UK asthma is the commonest chronic illness of children, but attempts to prevent childhood asthma have been largely unsuccessful. Epidemiological studies have suggested that exposure of a child before and after birth to tobacco smoke and air pollution increases their risk of developing asthma. A low consumption of fruit and vegetables and antioxidant vitamins (vitamins C, E and A) early in life may also increase risk. In the ALSPAC study we recently discovered that children with particular types of a gene called TRPA1 were more likely than children with other types of the gene to develop asthma. The TRPA1 gene controls a protein which is thought to increase inflammation of the airways in asthma, and the action of this protein is increased by harmful substances in the environment, such as tobacco smoke and air pollution.
We believe that children with ‘risky’ forms of the TRPA1 gene may be more likely than other children to develop asthma when they are exposed early in life to tobacco smoke and air pollution, or if their intake of protective antioxidants (from fruit, vegetables and vitamins) is low. We plan to test this hypothesis by analysing existing data in ALSPAC. In a subset of ALSPAC mothers and children we will also explore whether the risk of developing asthma partly depends on whether the TRPA1 gene is turned on or off. We will do this by measuring how much the DNA in the TRPA1 gene is chemically altered by a process called 'methylation'. Exposure to pollutants can alter the level of DNA methylation and this, in turn, can influence the extent to which a gene is turned on or off.
If we can confirm that infants who carry ‘risky’ forms of the TRPA1 gene are more likely to develop later asthma when exposed to harmful pollutants or a poor diet, this could help us to find ways to prevent childhood asthma from developing in the first place in these vulnerable individuals. For example, infants who are genetically susceptible in this way might particularly benefit from taking antioxidant vitamin supplements or from strategies designed to reduce their exposure to air pollution.

Impact of research: 
Deeper understanding of the potential role of TRPA1 in the aetiology of asthma and the mechanisms by which established early life risk factors might influence the development of asthma.
Date proposal received: 
Thursday, 1 December, 2016
Date proposal approved: 
Monday, 5 December, 2016
Keywords: 
Epidemiology, Allergy, Eczema, Respiratory - asthma, Epigenetics, GWAS, Statistical methods, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2801 - Effects of puberty timing on the metabolome - 2016/05/12

B number: 
B2801
Principal applicant name: 
Joshua Bell | IEU, University of Bristol (UK)
Co-applicants: 
Prof George Davey Smith
Title of project: 
Effects of puberty timing on the metabolome
Proposal summary: 

Early puberty may lead to the development of several different types of cancer in both men and women. This project aims to find out whether this increased cancer risk is partly due to adverse effects of early puberty on metabolism. To do this, we will examine links between genetic predispositions for timing of puberty and markers of body fat, along with a wide range of detailed blood-based markers of metabolic functioning. Data on ALSPAC mothers and children are particularly useful for seeing how genetic predispositions to early puberty affect fat and lean mass differently, and how these affect metabolic functioning at different stages of sexual maturity. Data on men from a separate cancer-specific study will also be examined to see how development of cancer affects links between puberty timing and metabolism. All results will be compared with those obtained from a separate analysis of genetic predispositions for puberty timing on metabolites using larger-scale collaborative data.

Impact of research: 
The immediate impact of this research will likely be at least 1 peer reviewed publication in a general medical journal (i.e. PLOS Medicine). We aim to present and discuss results in a way that is robust enough for academics but is accessible and relevant to clinicians and public health practitioners, ultimately encouraging greater attention to early life exposures and better prevention of disease.
Date proposal received: 
Friday, 2 December, 2016
Date proposal approved: 
Monday, 5 December, 2016
Keywords: 
Epidemiology, Cancer, Diabetes, Obesity, GWAS, Metabolomics, NMR, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Metabolic - metabolism, Puberty

B2799 - Associations between Adolescent Anxiety and Alcohol Use in Young Adulthood - 2016/05/12

B number: 
B2799
Principal applicant name: 
Maddy Dyer | IEU, School of Experimental Psychology, School of Social and Community Medicine (University of Bristol) (England)
Co-applicants: 
Professor Marcus Munafo, Professor Matthew Hickman
Title of project: 
Associations between Adolescent Anxiety and Alcohol Use in Young Adulthood
Proposal summary: 

Anxiety is associated with alcohol use. However, different hypotheses exist regarding the direction of these associations and evidence is inconsistent. Following on from a recent experimental study which found that state anxiety leads to higher alcohol choice, this epidemiological study will investigate the relationship between adolescent anxiety and alcohol use in young adulthood.

Impact of research: 
Anxiety and alcohol problems are both major public health concerns. It is important to investigate the direction of this relationship and factors which may affect the strength of this relationship. Identifying drinking-to-cope motive as a moderator could potentially inform targeted interventions for young people with anxiety, which in turn may reduce their risk of alcohol problems.
Date proposal received: 
Monday, 28 November, 2016
Date proposal approved: 
Monday, 5 December, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Mental health, anxiety, alcohol use, alcohol dependence

B2789 - Replication of var meQTLs - 2016/01/12

B number: 
B2789
Principal applicant name: 
Juan E. Castillo-Fernandez | Department of Twin Research, King's College London (UK)
Co-applicants: 
Gibran Hemani
Title of project: 
Replication of var meQTLs
Proposal summary: 

Quantitative trait loci (QTLs) studies have been successful identifying regions of the genome associated with inter-individual differences in DNA methylation. A common approach to explore the impact of genetic variants on DNA methylation is based on assessing differences in the mean methylation levels. However, QTLs may also contribute to the amount of variability of epigenetic marks (var QTLs). We identified var QTLs for DNA methylation in whole-blood using MZ twins-discordance as a measure of variability and are interested in the replication of these var meQTLs in an independent cohort.

Impact of research: 
Replication of our results will be crucial to ensure that the findings are robust. The research has the potential to suggest new mechanism through which genetic variation causes epigenetic variability and ultimately disease.
Date proposal received: 
Thursday, 17 November, 2016
Date proposal approved: 
Thursday, 1 December, 2016
Keywords: 
Genetics, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2792 - PEARL Assessment of pilot Police National Computer linkage exercise - 2016/01/12

B number: 
B2792
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
John Macleod, Rita Doerner, Matt Hickman, Joeseph Murray, Barbarra Maughan, Rosie Cornish
Title of project: 
PEARL: Assessment of pilot Police National Computer linkage exercise
Proposal summary: 

ALSPAC can collect information on participants life events through linking to their routine administrative records held by UK government. These are the records that all of us build up as we use government services (such as school records or GP records) or interact with government in other ways. For some participants, this will include records of criminal convictions and cautions. As part of ALSPACs work to establish these linkages we have conducted a pilot exercise linking some participants to their Police National Computer (PNC) database records (see project B557 for this work). The result of this linkage was a completely anonymous dataset, i.e. it includes ALSPAC participants PNC records, but cannot be linked to the ALSPAC dataset. In this project we would like to conduct simple comparisons of criminal records in this pilot exercise with participant reported criminality information provided at focus clinic and in questionnaires. The evidence will help inform the development of our linkage strategy.

Impact of research: 
We aim to advance the understanding of how criminal records can be linked to observational cohort studies.
Date proposal received: 
Monday, 21 November, 2016
Date proposal approved: 
Thursday, 1 December, 2016
Keywords: 
Epidemiology, Cohort studies - attrition, bias, participant engagement, ethics, Linkage, Criminality

B2797 - The relationship between flavonoids cognition and depression in children - 2016/01/12

B number: 
B2797
Principal applicant name: 
Amy Jennings | University of East Anglia (United Kingdom)
Co-applicants: 
Professor Aedin Cassidy, Faith Orchard
Title of project: 
The relationship between flavonoids, cognition and depression in children
Proposal summary: 

It is known that diet can have a significant impact on the development and function of the brain and growing evidence suggests links between diet, cognition and mood disorders. Dietary flavonoids are the most common polyphenolic compounds in the diet, they occur naturally in plant foods and are present in substantial amounts in commonly consumed fruits and vegetables. A number of plausible biological mechanisms link intake of flavonoids to both mood disorders such as depression and cognition, including an increase in blood flow to the brain which may lead to nerve cell growth and the formation of new blood vessels and a reduction in neuro-inflammation, an important contributor to depression. In a study of over 80,000 adults, we found that a higher intake of flavonoids from citrus fruits was associated with a 10% lower risk of depression (Chang et al. 2016). Furthermore, flavonoid clinical trials have reported significant benefits to cognition, mainly in the executive function (cognitive control) domain (Macready et al. 2009).

Adolescence is both a period of significant cognitive development and a period of high risk for developing mood disorders; thus it is an ideal time to target preventive interventions. This project will examine a number of commonly consumed flavonoid subclasses in order to assess which flavonoids are most effective for preventing low mood and cognitive dysfunction in children. Different flavonoid sub-classes have shown to differ in both bioactivity and bioavailability and are therefore likely to show differential associations with our outcomes.

Impact of research: 
There is increasing recognition of the importance of dietary risk factors to enhance well-being by improving mood and enhancing cognitive function. Data from the Mental Health of Children and Young People in Great Britain Survey indicates that 12% of young people aged 11–16 years have a clinically diagnosed mental disorder and 5% have an emotional disorder (anxiety or depression). Furthermore, the average age of onset for anxiety and mood disorders is 6 years and 13 years, respectively. It is therefore clear that depression and other mood disorders constitute a major public health problem with a significant personal, social and economic burden and the potential for early intervention using strategies targeted at improving dietary intake at a population level may be of substantial public health benefit. In order to be able to provide recommendations for clinical practice and information and support for dietary improvement to those with mood disorders dietary interventions are required. This work will provide much needed evidence to support the development of human trials that if targeted at young people have the potential to prevent the onset of mood disorders. Understanding more about how specific dietary components may promote health and well-being will also facilitate the development of more specific dietary guidelines for enhancing mood and cognitive function. Flavonoid research has the potential to make significant contribution to the knowledge base needed to refine the current, rather general, fruit and vegetable dietary recommendations.
Date proposal received: 
Monday, 28 November, 2016
Date proposal approved: 
Thursday, 1 December, 2016
Keywords: 
Epidemiology

B2781 - The neurodevelopmental consequences of prenatal alcohol exposure a population based MRI study - 2016/28/11

B number: 
B2781
Principal applicant name: 
Tamsin Sharp | Integrative Epidemiology Unit
Co-applicants: 
Dr Luisa Zuccolo, Professor Caroline Relton, Dr Esther Walton
Title of project: 
The neurodevelopmental consequences of prenatal alcohol exposure: a population based MRI study
Proposal summary: 

The association between heavy alcohol use in pregnancy and offspring neurodevelopmental defects is well established. However, studies examining low-to-moderate alcohol intake during the prenatal period have produced contradictory results, with some reporting beneficial effects to offspring. This project aims to utilise the existing neuroimaging data in ALSPAC to conduct a large scale population study to examine the relationship of low-to-moderate prenatal alcohol exposure and structural brain morphology in adolescence.

Impact of research: 
The impact of moderate drinking in pregnancy has long been debated, with some studies reporting a null or even protective effect. The results of this project, alongside parallel studies planned in Generation R and the Saguenay Youth Study, will be used to inform this field.
Date proposal received: 
Friday, 28 October, 2016
Date proposal approved: 
Monday, 28 November, 2016
Keywords: 
Neurology, Cognition - cognitive function, Development, Neurology, Neuroimaging, prenatal alcohol exposure

B2798 - Adolescent diet and cardiometabolic health - 2016/28/11

B number: 
B2798
Principal applicant name: 
Charlotte Evans | University of Leeds (UK)
Co-applicants: 
Miss Ziyi Li, Mrs Catherine Rycroft
Title of project: 
Adolescent diet and cardiometabolic health
Proposal summary: 

Worldwide the number of children and adolescents with risk factors for cardiovascular disease such as obesity and high blood pressure is increasing. Prevention strategies to reduce blood pressure and obesity are a national and international public health priority.
The relationships between diet and obesity and cardiovascular risk factors such as high blood pressure have been studied in adult populations but there are fewer corresponding studies in adolescents.
This project aims to
• Explore the relationships between diet, body size and adiposity, blood pressure and biomarkers for cardiovascular health (such as serum lipids and serum tocopherols) in UK adolescents from the ALSPAC cohort.
• Determine aspects of diet that increase children’s and adolescents’ likelihood of future obesity and high blood pressure.
• Develop a dietary based risk tool to identify groups of young people at high risk of future obesity during their teenage years.

Impact of research: 
The research will be the first to explore the longitudinal association between diet, biomarkers, body size and blood pressure in UK adolescents. The studies will provide informative results to help develop strategies to control obesity and elevated blood pressure in UK children and adolescents. In addition the study sets out to equip health professionals with a practical obesity risk tool. Preventing obesity is a major public health challenge but resources are finite; the tool could be used to identify populations at risk of obesity in order to target public health messages and interventions designed to reduce the risk of adolescent obesity more effectively. In addition it may be possible to use the tool to measure change in risk as a way of evaluating the effectiveness of an intervention.
Date proposal received: 
Monday, 28 November, 2016
Date proposal approved: 
Monday, 28 November, 2016
Keywords: 
Epidemiology, Hypertension, Obesity, Computer simulations/modelling/algorithms, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Blood pressure, BMI, Cardiovascular, Childhood - childcare, childhood adversity, Nutrition - breast feeding, diet, Adolescence, Obesity

- Peer networks and adolescents depressive symptoms - 2016/28/11

B number: 
Principal applicant name: 
Emily Chau | University College London (Division of Psychiatry)
Co-applicants: 
Professor Glyn Lewis, Dr Gemma Lewis
Title of project: 
Peer networks and adolescents' depressive symptoms
Proposal summary: 

There has been evidence to suggest that adolescence is associated with depression onset. A potential risk factor for adolescent depression is depressive symptoms in peers. Previous studies have shown linear association between peer depressive symptoms and adolescent depressive symptoms in dyads or small groups of friends, but none on how the configuration of social networks (e.g. number of degrees of separation from depressed social contact) influences adolescents’ depressive symptoms. Using this approach allows us to visualise adolescents’ social space, and expands our understanding of relationship of the peer network to adolescents' depressive symptoms.

This study aims to improve on previous studies' methods of adjustment. This study aims to identify friendship networks of 16 year-old adolescents, and investigate the effect of peers' depressive symptoms on adolescents’ depressive symptoms. It is hypothesized that there will be an association between peer depressive symptoms and adolescents' depressive symptoms. This study also aims to use structural properties of the friendship network (e.g. degrees of separation) to further investigate the relationship between the peer network and adolescents' depressive symptoms.

Impact of research: 
This study will add to our understanding of how surrounding peers might affect levels of depressive symptoms in adolescents, and in the process give greater insight to a possible cause of depression in adolescents. This is also important for identifying adolescents at risk of having increased levels of depressive symptoms due to aspects of their peer networks, and for designing and implementing early interventions for depression in the context of peer groups rather than individual work.
Date proposal received: 
Friday, 25 November, 2016
Date proposal approved: 
Monday, 28 November, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Statistical methods

B2786 - Investigation of the causal effects of atopic eczema on other health outcomes - 2016/28/11

B number: 
B2786
Principal applicant name: 
Lavinia Paternoster | MRC IEU (United Kingdom)
Co-applicants: 
Ashley Budu-Aggrery, Prof George Davey Smith, Prof Caroline Relton
Title of project: 
Investigation of the causal effects of atopic eczema on other health outcomes
Proposal summary: 

Atopic eczema affects up to 30% of children and 10% of adults. Individuals with eczema have been shown to be at higher risk of many other conditions (other atopic conditions – asthma and hay fever, ADHD, depression, autoimmune conditions) and at decreased risk of others (psoriasis and some cancers). However, from these observational associations it is not possible to establish whether eczema is causally related to these other conditions (and hence whether effective early treatment of eczema would alter the risk of these conditions) or whether the observational associations could be explained by common mechanisms (pleiotropy) or even reverse causation (whereby the early manifestations of the other conditions might influence a child’s risk of eczema). These diverse mechanisms are important to disentangle as they have important and different implications for the direction of future research into management and novel therapeutics for eczema as well as these other conditions.

We have recently carried out the largest ever genome-wide association study of eczema, identifying 24 genetic risk loci in Europeans. Using a technique called Mendelian randomization it is possible to use these genetic instruments to investigate the ‘causal’ nature of the associations with other conditions and therefore establish whether early effective treatment of eczema would have long term health implications far beyond just that of the eczema itself, potentially influencing the risk of life threatening conditions. Through an increased understanding of genetic overlap between eczema and other conditions, this analysis also has the potential to identify novel therapeutic targets.

Impact of research: 
Eczema sufferers are at increased risk of some serious later health complications, but it is unclear whether eczema is causally related to these conditions or whether other mechanisms explain these comorbidities. Early successful treatment of eczema is important for controlling the immediate symptoms of eczema. If the relationships are causal, it could also have far greater long-term health benefits. Mendelian randomization analysis provides a unique opportunity to better understand causal relationships. It may provide important evidence of the far-reaching impact that early successful treatment of eczema might have and also offers the opportunity to identify novel therapeutic targets.
Date proposal received: 
Monday, 7 November, 2016
Date proposal approved: 
Monday, 28 November, 2016
Keywords: 
Genetics, Allergy, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Eczema, Mental health, Obesity, Statistical methods, Mendelian randomization, Dermatology, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

- exploring the interaction between early life protective factors and early life stressors on mental health outcomes - 2016/28/11

B number: 
Principal applicant name: 
Ian Colman | University of Ottawa (Canada)
Co-applicants: 
Mrs. Gabrielle Dupuis
Title of project: 
exploring the interaction between early life protective factors and early life stressors on mental health outcomes
Proposal summary: 

Given our growing knowledge of the impact that mental health has on the individual and society it becomes imperative that we investigate the factors that serve to increase or decrease mental health. Research to date has tended to focus on proximal factors that may cause mental health disorders. This proposed research aims to investigate the interaction between early life stressors and early life protective factors and their impact on adolescent mental health outcomes. The overall objective of this research is to contribute to a better understanding of factors affecting mental illnesses experienced by children and youth. It is hoped that this research may contribute to the body of knowledge of preventative measures that can be taken especially as regards to prenatal, postpartum and early childhood care.

Impact of research: 
The burden and impact that mental illness has on individuals and society as a whole is continuing to grow. While there is a vast amount of knowledge pertaining to distal risk factors, more research needs to be conducted based on the positive youth development approach. Understanding the trajectory of early life stressors and how they can be mitigated by early life modifiable and non-modifiable protective factors can help to provide the public with methods in which they can help shape the lives of youth in a positive way, ultimately reducing their risk of developing adverse mental health outcomes. By understanding the impact of early life protected factors, targeted health promotion and intervention programs can be established. The results will be presented at national and international conferences, and manuscripts will be prepared for publication in scientific journals. Given the unique nature and high quality of the cohort data to be used, with repeated measures over several years, it is expected that the work will be published in top medical journals. In addition, it is anticipated that the media, policy-makers and clinicians will be interested in the results of this project.
Date proposal received: 
Tuesday, 8 November, 2016
Date proposal approved: 
Monday, 28 November, 2016
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Childhood - childcare, childhood adversity, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Offspring, Parenting, Psychology - personality, Physical - activity, fitness, function, Statistical methods

B2785 - Exposure to Endocrine Disrupting Chemicals and DNA Methylation - 2016/14/11

B number: 
B2785
Principal applicant name: 
Paul Yousefi | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdon)
Co-applicants: 
Dr Matthew Suderman, Prof. Caroline Relton
Title of project: 
Exposure to Endocrine Disrupting Chemicals and DNA Methylation
Proposal summary: 

It is widely accepted that early life influences shape our development and health and behavioural outcomes across the lifecourse. Epigenetic mechanisms are increasingly implicated in these complex interactions and provide a key to understanding (i) what aspects of our environment impact upon gene regulation, (ii) how our environment and way of living become embodied in human biology, over what time frame and with what degree of persistence and (iii) how social and biological inequality may influence development and health.

Environmental chemicals which are known to interfere with the intra-cellular signalling and regulatory effects of human hormones (particularly the male and female sex hormones, respectively androgen and estrogen) are collectively termed endocrine disrupting chemicals (EDCs). Exposure to anti-androgenic EDCs, especially during critical perinatal developmental period, is thought to have broad biological effects, possibly contributing to increased risk of congenital malformations of the reproductive tract and male infertility. However, detailed mechanistic characterisation of the impacts of exposure to EDCs, especially to broad regulatory features such as epigenetic modifications, has yet to be performed.

This project builds upon a substantial foundation of epigenetic research in richly
characterised longitudinal cohort studies to explore how early life EDC exposures may perturb the epigenome. We will utilise the Avon Longitudinal Study of Parents and Children, which currently has the most extensive collection of longitudinal epigenetic data of any birth cohort study in the world, as a platform to address the impact of EDC exposures. Specifically, we will utilize the exposure measurements of the CONTAMED (contaminant mixtures and human reproductive health) study which previously measured several potential EDCs (paracetamol, dichloro-anilines, phthalate metabolites, bisphenol A, triclosan, o-phenylphenol, and parabens) in three different types of biological samples (urine, plasma, placenta), to understand how these compounds influence epigenetic signatures and downstream outcomes.

Impact of research: 
The primary academic beneficiaries of this project will be environmental and biological scientists who will gain insight into the role of the epigenome and environmental exposures. Researchers in the field of lifecourse epidemiology will benefit from a clearer understanding of the role of epigenetic mechanisms in the programming of later health and behaviours. Academics at all career stages, from PhD students to senior academics will have the opportunity to engage with and benefit from the research proposed.
Date proposal received: 
Friday, 4 November, 2016
Date proposal approved: 
Monday, 14 November, 2016
Keywords: 
Epidemiology, Congenital abnormalities, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, Epigenetics, Mass spectrometry, Microarrays, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Endocrine - endocrine disrupters, Environment - enviromental exposure, pollution, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B2773 - Genetic Risk for Language Difficulties and Depression in Adolescence Role of Childhood Maltreatment - 2016/09/11

B number: 
B2773
Principal applicant name: 
Umar Toseeb | Department of Psychology
Co-applicants: 
Dr Jenny Gibson, Dr Dianne Newbury, Dr Sarah Parry
Title of project: 
Genetic Risk for Language Difficulties and Depression in Adolescence: Role of Childhood Maltreatment
Proposal summary: 

Approximately 7% of children who start primary school in the UK have language difficulties. Children with a diagnosed language disorder have worse mental health compared to those without. Moreover, nearly 40% of children with a speech and language disability have experienced abuse (emotional, physical, & sexual), which is 4 times higher than children with no disability. Despite the serious implications, children with language difficulties often go un-noticed.

The project will identify the pathways that lead depression during adolescence. For example, it may be that children with high genetic risk for language difficulties, who experience childhood abuse, go on to have language difficulties, which then leads to depression during adolescence. If this were to be the case, it would allow for clinical psychologists and speech therapists to work with victims of childhood abuse to improve their language ability with a view to reducing the associated mental health difficulties.

Understanding the role of genetic language risk in the pathways from childhood abuse to depression symptoms in adolescence will inform targeted language based interventions for the most vulnerable children.

Impact of research: 
It is anticipated that at least one high quality academic peer reviewed academic publication will arise from this project. Additionally, findings will be disseminated to non-academic audiences to inform professional practice. If our hypothesis are supported, it will be one of the first steps towards genetically determined personalised intervention strategies for victims of childhood abuse and children with langauge difficulties.
Date proposal received: 
Monday, 24 October, 2016
Date proposal approved: 
Wednesday, 9 November, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Developmental disorders - autism, Mental health, Speech/language problem, DNA sequencing, Statistical methods, Childhood - childcare, childhood adversity, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Speech and language, Statistical methods

B2782 - How the early environment interacts with prenatal adversity and genetic susceptibility to moderate the risk for anxious and depr - 2016/09/11

B number: 
B2782
Principal applicant name: 
Hannah Sallis | MRC IEU, University of Bristol (UK)
Co-applicants: 
Dr Ashley Wazana, Dr Rebecca Pearson, Dr Jonathan Evans, Dr Michael Meaney, Prof Marinus van IJzendoorn, Dr Eszter Szekely, Dr Henning Tiemeier
Title of project: 
How the early environment interacts with prenatal adversity and genetic susceptibility to moderate the risk for anxious and depr
Proposal summary: 

The project aims to investigate how early life stressors influence later childhood psychopathologies, in particular symptoms of anxiety and depression. The interaction between genotype and prenatal adversity will also be investigated.

Impact of research: 
The ALSPAC cohort contains a wealth of information on childhood and adolescent psychopathologies as well as a range of environmental exposures at several time points. Information on genome-wide data is also available on a large subset of women and children.
Date proposal received: 
Tuesday, 1 November, 2016
Date proposal approved: 
Wednesday, 9 November, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Genomics - structural variants, Statistical methods, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Sex differences, Statistical methods

B2771 - Metabolomic profile of healthy children - 2016/07/11

B number: 
B2771
Principal applicant name: 
John Carlin | Murdoch Children's Research Institute & University of Melbourne (Australia)
Co-applicants: 
Prof. David Burgner, Prof Debbie Lawlor, Prof Kate Tilling, Dr Diana Dos Santos Ferreira, Dr Peter Wurtz
Title of project: 
Metabolomic profile of healthy children
Proposal summary: 

The "metabolome" refers to the entire array of small molecules (metabolites) of different types that are found in the body. Metabolites may be exogenous (e.g. from diet, drugs), or endogenous, reflecting the substrates, intermediates and products of biochemical reactions. Metabolites include amino acids, peptides, lipids and lipoproteins, organic acids and carbohydrates, as well as many smaller molecules.

Proton nuclear magnetic resonance (NMR) metabolomics, in contrast to the other main analytical tool (mass spectrometry), gives information regarding a few hundred larger intact molecules whose physiological roles are largely at least partly understood. NMR has higher reproducibility than mass spectrometry.

The Brainshake platform (https://www.brainshake.fi/biomarkers) allows simultaneous analysis of ~230 NMR metabolites on serum or plasma. This technology is increasingly applied to large adult cohorts, identifying metabolites individually and in combination that are strongly predictive of disease risk of various kinds, in particular cardiovascular. There are much fewer data in children, with only one published study to date. This reported the relationship between GlycA (a composite marker of inflammation derived from the NMR analysis) and obesity and fitness in early adolescence (Ref).

With local collaborators we have recently obtained Brainshake metabolomic data for two population-based cohorts (and a number of smaller groups of children) in Victoria, Australia, and are seeking to combine these data with other large series internationally in order to characterise the age-related development of the metabolome across childhood in normal healthy children. This will provide important information that will enable us and others to interpret the significance of metabolomic data from a range of clinical populations. As far as we are aware (including personal communication with Peter Wurtz of Brainshake), the age- and sex-related profile of the metabolome across childhood is largely unknown.

Impact of research: 
New understanding of how metabolite profiles change during childhood and early adulthood will feed into new knowledge on the development of disease risk in the early life-course.
Date proposal received: 
Friday, 21 October, 2016
Date proposal approved: 
Monday, 7 November, 2016
Keywords: 
Epidemiology, Metabolomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Cardiovascular, Childhood - childcare, childhood adversity, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B2772 - Genetic Risk for Language Difficulties and Depression in Adolescence The Role of Childhood Maltreatment - 2016/07/11

B number: 
B2772
Principal applicant name: 
Umar Toseeb | Department of Psychology
Co-applicants: 
Title of project: 
Genetic Risk for Language Difficulties and Depression in Adolescence: The Role of Childhood Maltreatment
Proposal summary: 

Approximately 7% of children who start primary school in the UK have language difficulties. Children with a diagnosed language disorder have worse mental health compared to those without. Moreover, nearly 40% of children with a speech and language disability have experienced abuse (emotional, physical, & sexual), which is 4 times higher than children with no disability. Despite the serious implications, children with language difficulties often go un-noticed.

The project will identify the pathways that lead depression during adolescence. For example, it may be that children with high genetic risk for language difficulties, who experience childhood abuse, go on to have language difficulties, which then leads to depression during adolescence. If this were to be the case, it would allow for clinical psychologists and speech therapists to work with victims of childhood abuse to improve their language ability with a view to reducing the associated mental health difficulties.

Pathway analyses afford the examination of multiple factors and different potential routes: how children may get from A to B. It also affords the evaluation of the strength of different pathways and the assessment of the extent to which outcomes in different areas of functioning derive from common or distinctive routes. Part of the strength of this proposal is the inclusion of a variety of factors: genetic, environmental, and psychological in the same model.

Understanding the role of genetic language risk in the pathways from childhood abuse to depression symptoms in adolescence will inform targeted language based interventions for the most vulnerable children.

Impact of research: 
It is anticipated that at least one high quality academic peer reviewed academic publication will arise from this project. Additionally, findings will be disseminated to non-academic audiences to inform professional practice. If our hypothesis are supported, it will be one of the first steps towards genetically determined personalised intervention strategies for victims of childhood abuse and children with langauge difficulties.
Date proposal received: 
Friday, 21 October, 2016
Date proposal approved: 
Monday, 7 November, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Developmental disorders - autism, Mental health, Speech/language problem, DNA sequencing, Statistical methods, Childhood - childcare, childhood adversity, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Speech and language, Statistical methods

B2774 - Genetic markers of tanning dependence and sun exposure in childhood and adolescence - 2016/07/11

B number: 
B2774
Principal applicant name: 
Jasmine Khouja | PhD Student at the University of Bristol (United Kingdom)
Co-applicants: 
Carolina Bonilla, Sarah Lewis
Title of project: 
Genetic markers of tanning dependence and sun exposure in childhood and adolescence
Proposal summary: 

The project aims to investigate the association between genetic markers of tanning dependence and behavioural outcomes such as time spent in the sun or using tanning beds, having had bad sunburn as a child as well as investigate any associations with phenotypes such as the amount of freckles or moles a person has.

Impact of research: 
By exploring the associations between genetic variants linked to tanning dependence or other forms of addiction and tanning related behaviours or phenotypes in childhood, we will inform targeted interventions for at risk individuals.
Date proposal received: 
Tuesday, 25 October, 2016
Date proposal approved: 
Monday, 7 November, 2016
Keywords: 
Genetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods

B2777 - Understanding causality in associations between neuoticism and substance use - 2016/07/11

B number: 
B2777
Principal applicant name: 
Suzi Gage | MRC IEU (UK)
Co-applicants: 
Professor Marcus Munafo, Dr Hannah Sallis
Title of project: 
Understanding causality in associations between neuoticism and substance use
Proposal summary: 

Substance use and substance abuse occur at much higher levels in populations with mental health problems than in the general population, but the reasons for this are hard to untangle. Does poor mental health cause substance use, does substance abuse increase the risk of mental health problems, or are both affected by earlier life experiences? In order to try and untangle causality, methods such as Mendelian randomization can be used, where genetic predictors are used as proxies for confounded associations.

Impact of research: 
A better understanding of the associations between substance use and mental health can benefit the community as interventions to improve health can be more accurately targeted. We hope our findings will add to the literature attempting to unpick these associations and help with this.
Date proposal received: 
Wednesday, 26 October, 2016
Date proposal approved: 
Monday, 7 November, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition

B2778 - To identify and validate novel causal genetic variation for type 1 diabetes - 2016/07/11

B number: 
B2778
Principal applicant name: 
Brent Richards | Lady Davis Institute (Quebec)
Co-applicants: 
Andrew Paterson, Nicholas Timpson
Title of project: 
To identify and validate novel causal genetic variation for type 1 diabetes
Proposal summary: 

T1D is an unrelenting chronic disease of childhood that places a substantial burden on children and their families. This onus is increasing rapidly as the annual incidence rate of T1D is growing by ~5% per year in developed countries, such that by 2020 the number of children in Europe with T1D will increase by 70% from 2005 levels. T1D leads not only to a reduced lifespan by 12 years, but also to increased rates of renal failure requiring life-long dialysis, blindness, limb amputation, coronary heart disease and stroke. This study aims to use ALSPAC genotype data as controls in the replication of genetic association findings found to be associated with risk of T1D.

Impact of research: 
Through successful replication of our discovery GWAS findings, we will address the clinically relevant problem of identifying proteins influencing risk of T1D proteins, thereby offering drug-targets for an entirely novel approach to prevent a common and costly disease. Further, through MR studies, we will test whether modifiable risk factors (vitamin D and omega-3 fatty acids) play an important role in the etiology of T1D, thereby providing evidence to support, or prevent, large-scale RCTs to test these interventions to reduce T1D incidence.
Date proposal received: 
Thursday, 27 October, 2016
Date proposal approved: 
Monday, 7 November, 2016
Keywords: 
Genetics, Diabetes, Gene mapping, GWAS, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2627 - Tracking the developmental significance of sleep transition in early childhood - 2016/02/11

B number: 
B2627
Principal applicant name: 
Karen Thorpe | Queensland University of Technology (Australia)
Co-applicants: 
Dr Peter Blair, Associate Professor Simon smith, Dr Sally Staton, Associate Professor Helen Heussler, Dr James McGree, Professor Monique LeBourgeoius, Cassandra Pattinson
Title of project: 
Tracking the developmental significance of sleep transition in early childhood
Proposal summary: 

Sleep matters to those who care for young children. The duration and timing of sleep can have a profound effect on a young child’s everyday behaviour, learning and health and also has a significant impact on the routines and wellbeing of the adults who provide his or her care . Yet there is surprisingly little evidence regarding the developmental function of early sleep patterning to guide care practice. Current understanding of the processes underpinning the normative transition from multiple sleep wake cycles seen in infancy (polyphasic sleep) through to consolidation of sleep into a single night period (monophasic sleep) is limited. Age at cessation of napping occurs anywhere between age 1 and 5 years but we do not know whether this timing holds significance for long–term behavior, learning and health. Care practices almost certainly influence this timing but we do not understand in what way or to what effect. Understanding the developmental meaning of changing sleep patterns, the association of individual sleep patterns with variation in care environments and the pathway from these to long-term child outcomes are all necessary steps in identifying appropriate care. This knowledge will inform policy and practice in childcare settings where management of sleep is an issue of controversy and also inform parenting practice where early child sleep behaviours can have a major impact on family functiioning, parent wellbeing and child development

Impact of research: 
The focus of our research is particularly important in informing care practices with relation to sleep in early childhood settings and family contexts Internationally the importance of sleep for long term health is growing but the available evidence and subsequent guidance for policy and practice is limited. In Australia and The USA, for example, while there are significant recommendations for excercise and nutrition for young children existing recommendations for sleep are limited to sleep safety in the first year. We seek to inform such guidelines and are pleased to have within the team. Dr Peter Blair who has been so influential in informing sleep prcatices and sleep safety for youg children
Date proposal received: 
Sunday, 7 February, 2016
Date proposal approved: 
Wednesday, 2 November, 2016
Keywords: 
sleep science, developmental psychology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, sleep problems/disorders, Statistical methods, Childhood - childcare, childhood adversity, Development, Sleep

Pages