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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B3090 - Epigenetics in peer victimization and behavioural and emotional development - 05/04/2018

B number: 
B3090
Principal applicant name: 
Matthew Suderman | Integrative Epidemiology Unit (UK)
Co-applicants: 
Rosa Mulder, MSc, Esther Walton
Title of project: 
Epigenetics in peer victimization and behavioural and emotional development
Proposal summary: 

Peer victimization is a widespread phenomenon with many harmful and persistent consequences, such as anxiety, depression, and even suicidal ideation. However, consequences of can vary widely in presentation and severity, which hinders development of appropriate interventions targeted at alleviating the effects of peer victimization. This may in part stem from the fact that little is known about the biological mechanism through which bullying affects children's psychological development and wellbeing. Therefore, we aim to study how peer victimization is related to epigenetic development and explore to what extent epigenetics mediate the association between peer victimization and negative outcomes in children. We will do this by combining data of two large comparable cohorts, ALSPAC in England and Generation R in Holland.

Impact of research: 
Findings could offer novel insights into the role of epigenetics in bullying and child psychological outcomes.
Date proposal received: 
Monday, 26 March, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Computer simulations/modelling/algorithms, Childhood - childcare, childhood adversity, Epigenetics

B3118 - Genome-wide association study of anxiety and depression - 24/05/2018

B number: 
B3118
Principal applicant name: 
Nicholas Timpson | ALSPAC/IEU
Co-applicants: 
Mr Alex Kwong, Professor Cathryn Lewis, Dr John Hettema
Title of project: 
Genome-wide association study of anxiety and depression
Proposal summary: 

Genome-wide association studies (GWAS) have been instrumental in highlighting associations between genetic variants and 1000s of traits. A recent GWAS of major depressive disorder (MDD) by the psychiatric genetics consortium (PGC) has recently identified 44 genetic variants associated with the disorder (Wray et al., 2018). We plan to include ALSPAC data from the mothers and the children in the next round of analysis for both forthcoming MDD and anxiety PGC GWAS. We will prepare summary statistics from the GWAS to be shared with the PGC and perform subsequent in cohort analysis. This will be a big step towards incorporating ALSPAC data into psychiatric genetics. The summary statistics will contain no identifiable information.

Impact of research: 
These will be the largest GWAS on both MDD and anxiety disorders
Date proposal received: 
Wednesday, 23 May, 2018
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, GWAS, Genome wide association study

B3133 - Exploring the longitudinal effect of early maturation on physical and mental wellbeing - 14/06/2018

B number: 
B3133
Principal applicant name: 
Fiona Gillison | University of Bath (United Kingdom)
Co-applicants: 
Dr Sean Cumming, Dr Lauren Sherar, Ms Irma Fehratovic
Title of project: 
Exploring the longitudinal effect of early maturation on physical and mental wellbeing
Proposal summary: 

Research suggests that children who reach puberty early are at risk of poorer health and wellbeing. Such ‘early maturing’ children also tend to take part in riskier health behaviours, such as smoking, drinking alcohol and risky sexual activity. However, most studies look at these links at a single point in time, which limits how confident we can be that early maturing causes poorer wellbeing. Few studies have looked at what factors may increase or decrease some of these risks. Our study aims to use the ALSPAC data explore three questions relating to the longer-term health risks of adolescents who mature early. The first builds on work we have done with parents, showing many believe we should judge whether or not a child is overweight differently if they are an early maturer, to avoid labeling them as overweight when they are not. This is a particularly important time to consider how we respond to children's weights, as it is the point at which over 95% of children in England are weighed and measured as part of the National Child Measurement Programme. Some parents have been strong critics of this process, so public health teams and parents alike are interested in exploring how we could interpret and use this information better. To explore whether it is appropriate to use the same means of classifying early and on-time maturers as overweight, we will apply an adjustment for maturity to our calculations of weight status for children at age 11, and explore whether this is a better way of predicting which children will have higher/lower future health risks at age 17 (including obesity, blood pressure and other risk factors). Second, we will compare which factor at at age 10/11 is the stronger predictor of wellbeing in later adolescence; being overweight, or maturing early. Finally, to explore what factors might help children to avoid some of the potential consequences of maturing early, we will look at whether children’s views of the strength and importance of their relationships with parents and peers influence the effect of being an early maturer on their wellbeing by the age of 17 (including depression, positive wellbeing, and risk behaviours such as smoking and drinking).

Impact of research: 
This study will contribute to an increasing body of work exploring how we should use NCMP data being undertaken by the lead investigator. Depending on the findings, it will inform future funding applications and work with policy makers (namely PHE in the first instance) aiming to find better ways of engaging with parents of overweight children in ways that are meaningful to them to help children to maintain a healthy weight in childhood, and experience subsequent benefits to their physical and mental health. It will provide a case study of how we can learn from one field to apply it to another (e.g., applying Dr Cumming's work on biobanding to relevant health settings), developing our understanding of the more individual health and health-preventive needs of adolescents.
Date proposal received: 
Wednesday, 13 June, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Obesity, Statistical methods, BMI, Development, Psychology - personality, Physical - activity, fitness, function, Puberty, Sex differences, Social science

B3067 - DNA methylation and brain structure - 01/03/2018

B number: 
B3067
Principal applicant name: 
Esther Walton | University of Bristol - IEU
Co-applicants: 
Title of project: 
DNA methylation and brain structure
Proposal summary: 

Studies highlighted the role of genetic variation in brain anatomy (Hibar et al., 2015), but environmental factors might also be involved. The aim of the current study is to investigate to what degree epigenetic variation (DNA methylation) at birth is associated with brain structure across different ages. Secondary analyses aim to follow-up on promising methylation markers at later time points.
This project is part of a collaborative effort within the PACE consortium.

Impact of research: 
Findings could lend novel insights into the epigenetic landscape of brain structure.
Date proposal received: 
Thursday, 15 February, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Medical imaging, Biological samples -e.g. blood, cell lines, saliva, etc., Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Equipment - MRI, Epigenetics, Offspring

B3561 - Exploring how much complex trait variation is captured by DNA methylation in epigenome-wide association studies - 23/06/2020

B number: 
B3561
Principal applicant name: 
Gibran Hemani | MRC IEU
Co-applicants: 
Mr. Thomas Battram, Professor Tom Gaunt, Professor Nicholas Timpson
Title of project: 
Exploring how much complex trait variation is captured by DNA methylation in epigenome-wide association studies
Proposal summary: 

There are small chemicals that can be added to or removed from genes. These chemical changes may be related to changes in various human traits. For example smoking may cause a decrease in the number of these chemicals present at one or many genes. Currently it is not fully understood how these chemical changes are related to changes in human traits and this project aims to assess how chemical changes across many genes may relate to changes in human traits.

Impact of research: 
Date proposal received: 
Monday, 22 June, 2020
Keywords: 
Molecular genetics and genomics, Microarrays, Epigenetics

B604 - The association of birth weight with physical and cognitive development of schoolchildren population based birth weight standards versus customised birth weight standards

B number: 
B604
Principal applicant name: 
Dr H Wildschut (Erasmus University Medical Center, Rottterdam, the Netherlands, Europe)
Co-applicants: 
Ms Maarjot Danen (Not used 0, Not used 0), Mr Jesper A van Deenan (Not used 0, Not used 0)
Title of project: 
The association of birth weight with physical and cognitive development of schoolchildren: population based birth weight standards versus customised birth weight standards.
Proposal summary: 

Fetal growth is an important indicator of fetal well-being. The timely detection of pathologically impaired fetal growth is a prerequisite for the quality of antenal care, because of its apparent links to perinatal morbidity and mortality1, as well as adverse effects in childhood and later life2.

The prevalence of impaired fetal growth depends on the definition used. Population-based birth weight standards define 'small for gestational age' as the lowest tenth or fifth percentile, or as two standard deviations below the main birth weight for gestational age. This definition, however, includes 'natural' smallness. Therefore, it is essential to adjust for this normal variation in order to identify those infants who are pathologically small. Maternal weight, height, ethnic origin, parity and the infant's gender have all been found to be significantly associated with physiological variation in birth weight3. Professor J Gardosi developed the so-called customised growth charts, which are based on a new definition of fetal growth, thereby focussing on fetal growth potential, which takes in account the aforementioned variables (www.gestation.net).

Customised birth weight percentiles allow distinction between small, healthy newborns and those who are pathologically small3. Individually adjusted birth weight percentiles are more clearly associated with Apgar scores, perinatal outcome and neonatal morphometry indices than the unadjusted birth weight percentiles4. In this context, however, the association with long-term morbidity, such as cognitive and physical development, has never been examined.

ALSPAC is a longitudinal population-based cohort study, which includes all variables needed to analyse the long-term effects of intrauterine growth restriction on physical and cognitive health of schoolchildren.

Date proposal received: 
Monday, 28 January, 2008
Keywords: 
Primary keyword: 

B3069 - Early-onset depression characterising development and identifying risks - 06/03/2018

B number: 
B3069
Principal applicant name: 
Frances Rice | Cardiff University
Co-applicants: 
Dr Stephan Collishaw, Prof Anita Thapar , Prof Valentina Escott-Price, Dr Ajay Thapar, Prof David Osborn, Dr Jon Heron, Victoria Powell, Alice Stephens
Title of project: 
Early-onset depression: characterising development and identifying risks
Proposal summary: 

Major depressive disorder (MDD) is the most common mental illness and is the single leading cause of years lived with disability. Depression that begins early (by the early 20s) predicts particularly poor mental health and social outcomes and a chronic and relapsing course of symptoms over time. The strongest and most common risk factor for early-onset MDD is depression in a parent – this risk is likely to involve both environmental and inherited components.

In this project, we will characterise the trajectory of depressive symptomatology over adolescence and early adult life. We will test whether antecedent risk and protective factors identified in previous work influence the trajectory of symptoms over time. We will develop an algorithm to quantify individual risk for early-onset depression.

Impact of research: 
This study will generate clinically relevant knowledge about how to identify early onset depression (chronic trajectory of depressive symptoms and depressive disorder). We aim to generate a number of impactful scientific papers. Beneficiaries of the research may also include: individuals affected by depression and their families, practitioners in health (primary and secondary care), education and social care who come into contact with depressed young people and their families as part of their professional work and agencies with roles in providing education for clinicians (e.g. Royal College of Psychiatrists)
Date proposal received: 
Friday, 16 February, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Development, Genetic epidemiology

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