Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B2905 - Identifying dietary influences on obesity risk in early childhood a change-in-change analysis - 22/06/2017

B number: 
B2905
Principal applicant name: 
Erica Kenney | Harvard T.H. Chan School of Public Health (United States)
Co-applicants: 
Steven Gortmaker, Rebecca Mozaffarian, Jessica Barrett
Title of project: 
Identifying dietary influences on obesity risk in early childhood: a change-in-change analysis
Proposal summary: 

As researchers have searched for ways to slow the obesity epidemic worldwide, compelling evidence from adult populations has emerged suggesting that intake of specific types of foods and beverages – for example, sugary drinks, desserts, and refined grain products -- heighten the risk of excess weight gain over time. Although many experts agree that early childhood (ages 0 to 5 years old) is likely a critical period for the development of habits that influence obesity risk, particularly diet, there is very little high quality evidence on how dietary factors may influence excess weight gain among young children. We propose utilizing dietary data from 3-day food records and body mass index (BMI) data collected among the Children in Focus sub-sample of the Avon Longitudinal Study of Parents and Children in order to study how changes in dietary intake relate to changes in BMI during early childhood, from 18 months to 5 years old. This research can help us identify whether increasing intake of certain foods and beverages is linked with an increased risk of excess weight gain among young children, and can help inform policy strategies to prevent childhood obesity.

Impact of research: 
This research will help identify whether certain foods and beverages are more or less obesogenic in early childhood. This will help other researchers and public health professionals interested in developing interventions to prevent obesity in childhood understand which foods and beverages may need to be targets for behavioral changes. This can also inform the development of large-scale food policies, such as feeding programs like the U.S. Special Supplemental Program for Women, Infants, and Children and the Child and Adult Care Food Program, to promote a healthy weight among children.
Date proposal received: 
Wednesday, 21 June, 2017
Date proposal approved: 
Thursday, 22 June, 2017
Keywords: 
Epidemiology, Obesity, Statistical methods, BMI, Nutrition - breast feeding, diet

B2902 - GWAS on Childhood Blood Pressure and Related Traits - 22/06/2017

B number: 
B2902
Principal applicant name: 
Michelle Taylor | Integrative Epidemiology Unit, University of Bristol (UK)
Co-applicants: 
Dr Tarun Ahluwalia, Prof. Debbie Lawlor, Dr. Nic Timpson
Title of project: 
GWAS on Childhood Blood Pressure and Related Traits
Proposal summary: 

High blood pressure, which affects millions of people worldwide, is a major risk factor for heart attacks, stroke and chronic kidney disease. Approximately 9 million deaths each year are attributable to high blood pressure, including >50% of deaths from coronary heart disease and stroke.
Genome-wide association studies (GWAS) have identified over 50 genetic loci influencing blood pressure in European populations. However, a lot of studies have been carried out in adults, with only one study focusing on children (<18 years age). As GWAS studies require large sample sizes, we aim to replicate this study with the inclusion of more cohorts to increase statistical power.
This study in children may help us identify the underlying genetic architecture of the vascular system better compared to adults as there are very few/no confounders in terms of medication or other lifestyle factors.

Impact of research: 
If this proposal is successful, ALSPAC will contribute to research that will identify the underlying genetic architecture of the vascular system better compared to adults and also contribute to knowledge of age-specific variation in blood pressure. This will be used to better understand the life-course genetics of blood pressure and related traits.
Date proposal received: 
Monday, 19 June, 2017
Date proposal approved: 
Thursday, 22 June, 2017
Keywords: 
Genetics, Hypertension, GWAS, Blood pressure

B2901 - Association of maternal and child BMI with cardio-metabolic health in adolescence via DNA methylation - 22/06/2017

B number: 
B2901
Principal applicant name: 
Andrea Baccarelli | Columbia University (USA)
Co-applicants: 
Mr. Jian Huang
Title of project: 
Association of maternal and child BMI with cardio-metabolic health in adolescence via DNA methylation
Proposal summary: 

Obesity is a major public health issue, especially in low- and middle-income countries. These countries also suffer from a heavier burden of cardiovascular disease (CVD). Obesity is associated with higher risk of CVD, possible pathways have been investigated, including chronic low grade inflammation and oxidative stress. A recent study gives evidence that adiposity may cause DNA methylation, a mechanism of altering DNA expression without changing DNA sequence. However, whether DNA methylation mediated the association of adiposity with CVD risk is not clear. This study aims to assess this potential mediated effect, and may therefore use DNA methylation to identify high risk group of CVD. And since DNA methylation has a potential to be reversed, this may also provide insight into CVD prevention among overweight and obese population.
Therefore, this study investigates whether maternal and child body mass index (BMI) is associated with cardio-metabolic risk score in adolescence, and whether this association is mediated by DNA methylation in cord blood and childhood. The cardio-metabolic risk score is derived as the mean of five physical or biological measurements related to cardiovascular disease, i.e. systolic blood pressure, waist circumference, insulin resistant, triglycerides and HDL-cholesterol.

Impact of research: 
This research may provide insight into using DNA methylation to identify high risk group of CVD, and to CVD prevention among overweight and obese population.
Date proposal received: 
Friday, 16 June, 2017
Date proposal approved: 
Thursday, 22 June, 2017
Keywords: 
Epidemiology, Cardiovascular risk score, Epigenetics, Statistical methods, BMI, Cardiovascular

B2900 - Predicting adult stature in British Youth - 21/06/2017

B number: 
B2900
Principal applicant name: 
Sean Cumming | University of Bath (UK)
Co-applicants: 
Dr Catherine Barnaby
Title of project: 
Predicting adult stature in British Youth
Proposal summary: 
Impact of research: 
If successful, the new method could provide a more accurate, reliable, and culturally specific predictor of adult stature and maturation in British youth. It will also provide a non-invasive method for estimating maturation status for use in both research and practice. This will enable researchers to better understand and control for maturation when conducting research. It will also provide practitioners with more accurate methods for estimating the maturation status of children in a variety of contexts, including schools, sport, and health.
Date proposal received: 
Thursday, 15 June, 2017
Date proposal approved: 
Wednesday, 21 June, 2017
Keywords: 
Developmental biology

B2898 - Father involvement and parenting in the context of maternal perinatal depression - 23/06/2017

B number: 
B2898
Principal applicant name: 
Iryna Culpin | School of Social and Community Medicine, University of Bristol (Bristol )
Co-applicants: 
Dr Rebecca Pearson
Title of project: 
Father involvement and parenting in the context of maternal perinatal depression
Proposal summary: 
Impact of research: 
There is distinct lack of research that examines father-child interactions in infancy and the impact fathers’ parenting has on child development, particularly in the context of perinatal depression. The insights gained as a result of this research are likely to be impactful and of critical importance to the field of early child development and perinatal mental health in families. They also have the potential to elucidate possible protective mechanisms (e.g., specific behaviours that improve quality of parent-child interactions) that could be translated into future parenting and psycho-educational interventions. Aside from examining father-child interactions in families affected by depression, very little research has been done so far to examine differences between maternal and paternal interactions with their infants in non-depressed families.
Date proposal received: 
Monday, 12 June, 2017
Date proposal approved: 
Tuesday, 13 June, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Novel wearable technology (parent and child head cameras) to measures parent-child interactions in naturalistic setting. , Childhood - childcare, childhood adversity, Development, Fathers, Offspring, Parenting

B2896 - Genome-wide association study of puberty growth - 12/06/2017

B number: 
B2896
Principal applicant name: 
Kaitlin Wade | MRC Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Nicholas J Timpson, Neil Davies, Joshua Bell
Title of project: 
Genome-wide association study of puberty growth
Proposal summary: 

The aim of this project is to investigate the genetic contribution to the timing, speed and duration of puberty growth in girls and boys of the Avon Longitudinal Study of Parents and Children. This project is an update on previous work conducted by the Early Growth Genetics (EGG) Consortium (Cousminer et al., 2013) with denser genetic data and a greater ethnic diversity in samples.

Impact of research: 
Date proposal received: 
Tuesday, 6 June, 2017
Date proposal approved: 
Monday, 12 June, 2017
Keywords: 
Genetics

B2891 - Population penetrance of functional MCR4 variants - 15/06/2017

B number: 
B2891
Principal applicant name: 
Audrey Melvin | Metabolic Research Laboratory (United Kingdom)
Co-applicants: 
Professor Sir Stephen O'Rahilly, Dr Giles Yeo
Title of project: 
Population penetrance of functional MCR4 variants
Proposal summary: 

It is estimated that a quarter of adults in the United Kingdom are obese. In addition to obesity being strongly heritable, the increased availability and affordability of energy dense foods has contributed to this global public health problem. However obesity can sometimes be caused by disorders of single genes. The Melanocortin 4 receptor (MC4R) is a gene that works in the brain to influence both appetite and how fast energy is burned off in the body. People who have mutations that disrupt the function of even just one of the two copies of the MC4R are often obese from early childhood. MC4R is the most common single gene disorder responsible for obesity and although estimates of its frequency in the population have been made, we don’t know exactly how common it is. We also don’t know exactly what the chances of a person carrying one bad copy of the MC4R gene has of becoming obese or when during their life this would start to be noticeable. To address this we will identify carriers of significant MC4R mutations by carrying out sequencing of the gene on DNA samples collected from the ALSPAC G1 cohort and by using our knowledge and lab testing to determine which mutations actually do impair the function of MC4R and which are just variations of normal

This work will tell us a) what the frequency of significant MC4R mutations are in a relatively unselected UK population b) how often such mutations lead to obesity

There are now trials ongoing of specific treatments for obesity associated with MC4R mutations. If those trials prove positive then it will be very important to know how many patients in the UK might benefit and to set up systems to identify MC4R deficient children

Impact of research: 
The study will provide valuable information on the prevalence of MC4R variants in the population. There are ongoing exploratory clinical trials of targeted therapy in this disorder. If these prove positive, then it will be important to understand the prevalence of the condition in the UK and to design systems to identify all children who might benefit from such therapies. Even without a specific therapy the clearer definition of the prevalence of functionally significant MC4R mutations may help embed genetic diagnostics into routine NHS services for children with obesity The Cambridge team would be blind to the identify of any children carrying such variants and would not therefore have any plans to feedback such information to participants. Our sequencing would be done in our University facilities and not a clinically accredited lab and therefore (though of high quality) would not formally be “clinical grade”. Based on our results the ALSPAC team may wish to consider whether the small number of children that we predict will have functionally significant MC4R mutations should have that information given to participants and their GPs. Should they decide to take this further, our clinical team would then, of course, be available to provide advice on further testing and clinical management. But any such activity would be wholly independent of this particular study,
Date proposal received: 
Monday, 5 June, 2017
Date proposal approved: 
Monday, 12 June, 2017
Keywords: 
Genetics, Obesity, DNA sequencing, Biological samples -e.g. blood, cell lines, saliva, etc., Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Metabolic - metabolism

B2895 - Lifestyle behaviours during pregnancy and offspring psychiatric outcomes Using Mendelian randomization to infer causality - 01/06/2017

B number: 
B2895
Principal applicant name: 
Hannah Sallis | MRC Integrative Epidemiology Unit, University of Bristol (UK)
Co-applicants: 
Dr Gemma Sharp, Prof Marcus Munafo
Title of project: 
Lifestyle behaviours during pregnancy and offspring psychiatric outcomes: Using Mendelian randomization to infer causality
Proposal summary: 

This project encompasses two PhD projects that will explore the association between maternal lifestyle behaviours during pregnancy and offspring psychiatric outcomes.

These projects will provide insights into whether there is a causal relationship between maternal substance use and offspring mental health symptoms, and the mechanisms underlying these associations. Although a number of exposures are currently known to be harmful to the developing foetus, the majority of research to date has focused on physical rather than mental health outcomes.

Impact of research: 
These projects will provide insight into whether parental substance use during pregnancy is causally related to offspring mental health symptoms. Although several exposures are already known to be harmful to the developing foetus, to date, research has mainly focused on physical health rather than mental health outcomes. In addition, project 2 will provide insight in the epigenetic pathways through which parental lifestyle behaviours during pregnancy exert their causal influence on downstream offspring psychiatric outcomes, and enhance our understanding of the mechanisms underlying these relationships. This approach will allow us to determine whether methylation of the child's DNA at birth underlies any causal effects of environmental exposures during pregnancy and psychopathology in childhood and adolescence.
Date proposal received: 
Thursday, 1 June, 2017
Date proposal approved: 
Thursday, 1 June, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Epigenetics, GWAS, Statistical methods, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Offspring, Psychology - personality, Statistical methods

B2894 - The impact of maternal folic acid supplementation during pregnancy and childrens psychosocial development - 21/06/2017

B number: 
B2894
Principal applicant name: 
Tony Cassidy | Ulster University (Northern Ireland)
Co-applicants: 
Lesley-Anne Henry, Dr Marian McLaughlin, Prof Colum Walsh, Dr Rachelle Irwin, Aoife Caffery, Kristina Pentieva, Helene McNulty
Title of project: 
The impact of maternal folic acid supplementation during pregnancy and childrens psychosocial development
Proposal summary: 

Folate is essential to the body to synthesize, repair and methylate DNA. During pregnancy there is an increased demand for folate to aid rapid cell division and growth which is vital for foetal, placental and maternal development (1), therefore folic acid (400ug/d) is recommended to all women from preconception to the end of the first trimester of pregnancy (2). The physical benefits of folic acid supplementation are well documented in the literature; the most notable is protection against first occurrence and reoccurrence of neural tube defects (3), which affects over 900 pregnancies per year in the UK (4). Supplementation has also been shown to reduce the risk of congenital heart defects (5), cleft palette (6). Premature delivery (7) and low infant birth weight (7).
In terms of neurocognitive development, deficiency in maternal folate levels has been shown to negatively impact on the child’s cognitive performance (8), whereas optimal levels positively impact on language and motor development at age four (9) and lower the risk of children Internalising and externalising problems (10;11).
At present UK policy recommendations clearly focus on the protective role of folate during the early stages of pregnancy however, the role of maternal folic acid supplementation during the later stages of pregnancy is less clear and it is unknown whether it confers any other long-term effects in the children.

Impact of research: 
Academically we plan to use these ALSPAC findings to validate the current literature regarding the impact of maternal folic acid use on various aspects of their children's development. In practice we aim to use our research findings to inform policy.
Date proposal received: 
Wednesday, 31 May, 2017
Date proposal approved: 
Wednesday, 31 May, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Childhood - childcare, childhood adversity, Psychology - personality, Cognition - cognitive function, Development, Growth, Intelligence - memory, Mothers - maternal age, menopause, obstetrics, Nutrition - breast feeding, diet, Offspring, Parenting

B2892 - Impact of economic conditions in year of birth on DNA methylation age acceleration - 31/05/2017

B number: 
B2892
Principal applicant name: 
Paul Yousefi | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdom)
Co-applicants: 
Gerard van den Berg, Dr. Matthew Suderman, Prof. Caroline Relton
Title of project: 
Impact of economic conditions in year of birth on DNA methylation age acceleration
Proposal summary: 

Macroeconomic conditions or business cycle status during year of birth have been found to have diverse impacts on later life health (e.g. cognitive function in later life, Doblhammer & van den Berg 2013). Epigenetic modifications are important biological regulatory mechanisms that undergo widespread remodeling during development, are susceptible to modification, and may mediate the impact of early-life environmental factors on later life health. We aim to examine to examine whether macroeconomic status at birth is associated with altered DNA methylation, particularly epigenetic age acceleration, in adults.

Impact of research: 
The primary academic beneficiaries of this project will be social epidemiologists, health economists, and biological scientists who will gain insight into how external social factors can alter the epigenome.
Date proposal received: 
Sunday, 28 May, 2017
Date proposal approved: 
Wednesday, 31 May, 2017
Keywords: 
Health Economics, Epigenetics, Microarrays, Ageing, Social science

B2893 - Is BP variability related to pregnancy outcome - 31/05/2017

B number: 
B2893
Principal applicant name: 
Laura A Magee | St. George's, University of London (UK)
Co-applicants: 
Richard McManus
Title of project: 
Is BP variability related to pregnancy outcome?
Proposal summary: 

Outside pregnancy, how much blood pressure varies is associated with the risk of heart attack, stroke and similar health problems.
In the CHIPS Trial (Control of Hypertension In Pregnancy Study) of 987 women with high blood pressure that was there before pregnancy or that developed in pregnancy, we found that the more blood pressure varied, the greater the risks for the mother, with possibly reduced risks for the baby. We are seeking to confirm whether these findings can be replicated in another dataset.

Impact of research: 
The concept of BP variability being related to pregnancy outcome is a new concept in obstetrics. It is a concept that clinicians can understand, as they reflect on their clinical practice and efforts to stabilise the BP of women whose values seem to 'bounce' around unpredictably. As such, clinicians will be interested in a potentially new predictive tool, especially if BP values can be entered into a mHealth application that updates risk. This work has the potential to have an impact on maternity care in more- and less-resourced settings.
Date proposal received: 
Monday, 29 May, 2017
Date proposal approved: 
Wednesday, 31 May, 2017
Keywords: 
Clinical research/clinical practice, Hypertension, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Blood pressure, Cardiovascular

B2889 - Paternal characteristics and lifestyle and offspring DNA methylation - 24/05/2017

B number: 
B2889
Principal applicant name: 
Gemma Sharp | MRC Integrative Epidemiology Unit
Co-applicants: 
Dr Luisa Zuccolo
Title of project: 
Paternal characteristics and lifestyle and offspring DNA methylation
Proposal summary: 

Although lots of studies have looked at the effect of maternal behaviours on offspring DNA methylation, there is a severe lack of studies looking at paternal characteristics. Increasingly, findings from animal models suggest that paternal exposures can affect offspring health via epigenetic changes to sperm. If this is true in humans, we might expect to see changes in cord blood DNA associated with paternal factors.
We plan to use epigenome-wide association studies in a consortium setting to investigate paternal-specific effects. This will require using strategies to overcome confounding by maternal effects and shared genetics.

Impact of research: 
One of the first studies of paternal effects on offspring DNA methylation. The findings will indicate whether we should be focusing further research on fathers and will have important implications for public health advice to men who are hoping to have children.
Date proposal received: 
Wednesday, 17 May, 2017
Date proposal approved: 
Wednesday, 24 May, 2017
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Epigenetics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Physical - activity, fitness, function, Birth outcomes, BMI, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Fathers

B2883 - Early Menarche and Risky Behaviours A Mendelian Randomisation Study - 17/05/2017

B number: 
B2883
Principal applicant name: 
Elizabeth Braithwaite | University of Oxford
Co-applicants: 
Professor Lucy Bowes
Title of project: 
Early Menarche and Risky Behaviours: A Mendelian Randomisation Study
Proposal summary: 

Timing of puberty has both short- and long-term impacts on physical and mental health for adolescent girls; understanding links between early puberty and health outcomes has important implications for healthcare and policy. This research concerns existing evidence for associations between early puberty in girls and risky behaviors. Such behaviors include risky sexual behaviors (including earlier sexual experiences, unprotected sex and teenage pregnancy) and risky health behaviors (such as alcohol and substance misuse). Although there have been numerous observational reports of links between early puberty and risky behaviors, there have also been inconsistencies. For example, some studies report associations to be persistent into adulthood, whereas others suggest that effects are only present in early, but not late, adolescence. Furthermore, observational studies have numerous limitations, including confounding, reverse causality and bias, which make findings difficult to interpret. Thus, it is currently unclear whether associations between early puberty and risky behaviors in girls may be causal. Although randomized controlled trials (RCTs) are considered the gold standard of epidemiological research methods, testing causal associations between early puberty and risky behaviors is not possible within an RCT design. Alternatively, Mendelian randomization allows the testing of causal relationships between exposure and outcome within a genetically informed design. We propose to test the causal relationship between early puberty in girls and risky behavior using a Mendelian randomization design.

Date proposal received: 
Wednesday, 10 May, 2017
Date proposal approved: 
Wednesday, 17 May, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Childhood - childcare, childhood adversity, Development, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Puberty

B2888 - Young people and gambling-related harm - 23/06/2017

B number: 
B2888
Principal applicant name: 
David Forrest | University of Liverpool Management School (United Kingdom)
Co-applicants: 
Prof. Ian G. McHale
Title of project: 
Young people and gambling-related harm
Proposal summary: 

It is not surprising that those exposed to gambling in adolescence through parental example are more likely to be active gamblers in young adulthood or that young people who had parents with gambling problems are more likely themselves to be problem gamblers. However, the source of these correlations is not understood. A typical pathway to gambling/ problem gambling in young adulthood may be direct: for example, having parents who gamble ‘normalises’ gambling for the young person or the parents actually introduce their children to gambling, facilitating their participation while still under-age. On the other hand, the correlations may not depend on the direct influence of parental behaviour with respect to gambling itself, which may indeed not be decisive. Rather parental gambling and especially problem gambling may serve as proxies for more general household characteristics such as attitude to risk, engagement in stigmatised activities and domestic instability.

The ALSPAC data set includes information on the young adult’s own gambling. Clearly these variables are required as central to the analysis; and we will also plan to include in modelling information on the respondent’s contemporaneous participation in other risky activities as well as standard controls such as educational qualifications.

Equally crucial to the hypotheses to be examined will be information on parental self-reported gambling at child ages 6 and 18. We are also requesting variables which reflect other aspects of parental lifestyle (primarily from mother and partner questionnaires at child age 12).

Impact of research: 
significant input into progressing the young persons theme for action under the National Responsible Gambling Strategy
Date proposal received: 
Tuesday, 16 May, 2017
Date proposal approved: 
Wednesday, 17 May, 2017
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, Parenting, Social science, Statistical methods

B2885 - Research to support an inquiry into young peoples future health prospects - 02/06/2017

B number: 
B2885
Principal applicant name: 
Heather Brown | Newcastle University (UK)
Co-applicants: 
Professor John Macleod, Professor Eileen Kaner, Professor Clare Bambra, Dr Raghu Lingam, Dr Ruth McGovern
Title of project: 
Research to support an inquiry into young people’s future health prospects
Proposal summary: 

This project will add to the evidence base on the relationship between health, socioeconomic factors, and service usage in young people. We will employ a holistic definition of health encompassing factors related to emotional well-being, housing, employment and employment prospects, health behaviours and general health. The outputs will be designed to be easily understood and be usable for a wide range of stakeholders. A key aim of this study is identify how socioeconomic inequalities may impact on health outcomes to identify vulnerable groups which may need additional support to reach their full potential. Work package 1 will be divided into two phases. The first stage will be a scoping review. The scoping review will provide an overview of the factors that impact on young people’s health. The second stage will explore how survey and administrative data can be used for statistical analysis to determine:
A1) The relationship between economic and social factors on young people’s health
A2) Provide preliminary analysis of how access to key services may impact on the young people’s social determinants of health
A3) Map young people’s service use in their adolescence and young adulthood in relation to their health and economic and social factors.

Impact of research: 
This research will guide the development of interventions and policy to help young people fulfil their potential by understanding who and when and where interventions should be targeted to improve young people's health and prospects.
Date proposal received: 
Friday, 12 May, 2017
Date proposal approved: 
Tuesday, 16 May, 2017
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Sexually transmitted diseases, chlamydia, gonorrhoea, Statistical methods, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Linkage, Social science

B2887 - Comparing outcomes in adults who were looked after or adopted as children - 17/05/2017

B number: 
B2887
Principal applicant name: 
Alison Teyhan | PEARL, ALSPAC
Co-applicants: 
Prof. John Macleod
Title of project: 
Comparing outcomes in adults who were looked after or adopted as children
Proposal summary: 

Looked after children are amongst the most vulnerable in society. They have experienced adversity in their family life at a level which necessitated the involvement of social services, resulting in the local authority taking on parental responsibility, and usually their removal from the family home. These children are known to do worse than their peers across many domains, including education, mental health, and social support. Fewer studies have considered later adulthood, and how the adversities faced by people who experience being in care as children persist or change over time. A minority of children are adopted from care, with the aim of giving them a permanent new family. Few studies have compared outcomes in adults who were adopted to those who remained looked after.

Date proposal received: 
Tuesday, 16 May, 2017
Date proposal approved: 
Tuesday, 16 May, 2017
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Childhood - childcare, childhood adversity

B2886 - Genetics of total and regional body composition - 17/05/2017

B number: 
B2886
Principal applicant name: 
Joshua Bell | IEU, University of Bristol (United Kingdom)
Co-applicants: 
Dr Kaitlin Wade, Dr Nicholas Timpson, Prof Dave Evans, Prof Jon Tobias, Dr Arimantas Lionikas
Title of project: 
Genetics of total and regional body composition
Proposal summary: 

This study aims to investigate genetic underpinnings of body composition among adults. By combining measures of total and regional body fat, lean, and bone mass with measures of common genetic markers among participating post-adolescents and mothers in ALSPAC, we aim to search for and describe specific genetic variants that may influence differences in body mass, and ultimately future disease, in a young and middle-aged adult population. Ultimately, this work will be combined with work done in other cohorts of similar-aged adults to increase the scope and reliability of results.

Date proposal received: 
Friday, 12 May, 2017
Date proposal approved: 
Tuesday, 16 May, 2017
Keywords: 
Genetics, Obesity, GWAS, BMI, Bones (and joints), Cohort studies - attrition, bias, participant engagement, ethics, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Physical - activity, fitness, function

B2884 - ADHD neuro-cogntive functioning and genes - 25/05/2017

B number: 
B2884
Principal applicant name: 
Guido Biele | Norwegain Institute of Public Health
Co-applicants: 
Title of project: 
ADHD, neuro-cogntive functioning and genes
Proposal summary: 

Attention deficit Hyperactivity disorder (ADHD) is a neuro-developmental disorder whose origins remain not well understood. Popular theories of ADHD assume that ADHD symptoms are caused by the dysfunction of specific neuro-cognitive mechanisms like the ability to represent and learn from positive and negative feedback (also called prediction errors) or the ability to hold information for further manipulation in the working memory. These neuro-cognitive functions depend on the availability of neurotransmitters (signalling molecules), in particular dopamine, in the brain. Yet, even though there is ample evidence for genetic influence on neurotransmitter availability, and twin studies indicate the heritability of ADHD, the specific genetic contributions to ADHD remain poorly understood.
This project shall use a “computational psychiatry” approach to improve the understanding the specific genetic contributions to ADHD. Computational psychiatry uses mathematical models of cognition and learning that are consistent with behavioural and neurobiological data to identify which neuro-cognitive sub-processes cause impaired learning or cognition. For example, impaired reward-based learning could be explained by the inability to learn from positive feedback or feedback, or to the inability to make choices consistent with learned reward-values. Low performance in cognitive tests could be caused by a low ability (resulting e.g. from noisy working memory representations), or by a preference for fast as opposed to accurate responding.
Because the mathematical models employed in this project have been shown to be good models of the cognitive and neuro-biological processes underlying learning and decision making, they can build a bridge between ADHD symptoms and genes by showing how neuro-cognitive deficits underlying ADHD are in turn associated with genes. We expect stronger associations between neuro-cognitive processes and genes than between ADHD-Symptoms and genes, because the former are likely more directly influence by genes.
Hence, our goals are to describe ADHD phenotypes in terms of neuro-cognitive sub processes obtained through mathematical modelling and to identify genes associated with these phenotypes.
For this aim we will model data from neuropsychological and experimental tests collected in the ALSPAC Teen focus data collections to first identify in which neuro-cognitive processes ADHD patients have the most important deficits. In a second step, we will investigate genetic associations for the neuro-cognitive processes with the largest deficits.

In sum, this project will use mathematical modelling of task performance to identify neuro-cognitive processes that mediate the influence of genes on ADHD symptoms. Modelling neuro-cognitive functioning will improve the understanding of ADHD and contribute to the definition of phenotypes that facilitate the detection of genetic contributions to ADHD.

Impact of research: 
We assume that the impact of the research will be large, because the “computational psychiatry” approach is a growing field that would get a major boost from publication of studies with large samples. More importantly, by using computational modelling as a bridge between the clinical level (ADHD symptoms) and the biological levels (genes) we hope to advance substantially the understanding of the genetics of ADHD.
Date proposal received: 
Thursday, 11 May, 2017
Date proposal approved: 
Tuesday, 16 May, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Attention deficit Hyperactivity disorder (ADHD), GWAS, Computational modelling of task data Bayesian hierarchical modeling candidate gene study GTCA, Cognition - cognitive function, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Linkage, Statistical methods, mental health computational modelling

B2882 - Haptoglobin and cardiovascular disease - 10/05/2017

B number: 
B2882
Principal applicant name: 
Tom Gaunt | MRC IEU, SSCM, University of Bristol (United Kingdom)
Co-applicants: 
Dr Nabila Kazmi, Dr Ian Galea
Title of project: 
Haptoglobin and cardiovascular disease
Proposal summary: 

Haptoglobin is one of the most abundant proteins in blood, and plays a role in protecting the body from harmful effects of another blood protein, haemoglobin. Haptoglobin may play an important role in altering the severity of outcomes after brain haemorrhage. We will use the ALSPAC cohort to measure the effects of genetic variants on the levels of haptoglobin. These genetic variants will then be used in a separate study to determine whether haptoglobin levels affect the severity or consequences of brain haemorrhage.

Date proposal received: 
Monday, 8 May, 2017
Date proposal approved: 
Wednesday, 10 May, 2017
Keywords: 
Neurology, Carotid artery intima thickness, GWAS, Cardiovascular, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Neurology

B2881 - Understanding the Antecedents and Outcomes of Adolescent Cannabis Use Trajectories - 10/05/2017

B number: 
B2881
Principal applicant name: 
Lindsey Hines | King's College London (to be affiliated with University of Bristol if fellowship application is successful)
Co-applicants: 
Professor Matthew Hickman, Professor Stanley Zammit, Dr Paul Moran, Dr Jon Heron
Title of project: 
Understanding the Antecedents and Outcomes of Adolescent Cannabis Use Trajectories
Proposal summary: 

Globally, cannabis is the most commonly used illicit drug. As cannabis policy is liberalising, there is an expected increase in adolescent use. This introduces an urgent need to understand what underlies harmful use, and to understand if cannabis plays a role in mental health disorder development. A key consideration in understanding the health impacts of cannabis is frequency of use. Cannabis dependence, characterised by loss of control over use and poor health and social functioning is more likely with frequent use. Yet, we know little about what factors determine frequency of use (and thus likelihood of related harm) among adolescents; a group in which use is high (40-70% prevalence), and for whom frequent use may lead to particularly poor mental health outcomes, including depression and anxiety
This fellowship will investigate trajectories of cannabis use among adolescents in the general population, exploring the role of Early Life Stress (ELS; a consistent correlate of use and dependence) in frequent cannabis use.

Date proposal received: 
Wednesday, 3 May, 2017
Date proposal approved: 
Wednesday, 10 May, 2017
Keywords: 
Epidemiology

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