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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B3083 - Exploring the relationship between bone turnover and serum levels of citrate - 16/03/2018

B number: 
B3083
Principal applicant name: 
Jon Tobias | University of Bristol (United Kingdom)
Co-applicants: 
April Hartley, Celia Gregson, Lavinia Paternoster
Title of project: 
Exploring the relationship between bone turnover and serum levels of citrate
Proposal summary: 

Osteoporosis is a metabolic disorder of bone, characterized by increased bone resorption. Serum collagen type 1 cross-linked C-telopeptide (CTX) is increased during bone resorption. In our preliminary metabolomic analysis, which aimed to identify the metabolic consequences of reduced bone turnover in a cohort of adults with high bone mineral density, we identified a positive relationship between serum CTX and NMR-assessed serum citrate levels (unpublished data). Citrate is a component of bone mineral with a potential structural function (Costello et al 2013). We aim to repeat our cross-sectional analysis of the association between serum CTX and serum citrate in both the ALSPAC mothers and adolescents population to determine if this association replicates, firstly in a general population cohort of a similar age, and secondly in a younger population, which would suggest that serum citrate is a novel marker of bone resorption.

Impact of research: 
If serum citrate is associated with bone resorption (CTX), with evidence for a causal association between CTX and citrate, serum citrate could be used as a novel biomarker of osteoporosis and to determine response to osteoporosis therapy.
Date proposal received: 
Thursday, 15 March, 2018
Keywords: 
Epidemiology, Bone disorders - arthritis, osteoporosis, GWAS, Mendelian randomisation

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

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

B603 - The effect of common disease associated genetic variants on transcriptomic and early life phenotypes

B number: 
B603
Principal applicant name: 
Dr Dave Evans (University of Bristol, UK)
Co-applicants: 
Title of project: 
The effect of common disease associated genetic variants on transcriptomic and early life phenotypes
Proposal summary: 

ALSPAC has pre-existing data on transcriptomic and phenotype variables related to disease. This is necessary in order to assess the effect of known disease causing variants in early life phenotypes.

Date proposal received: 
Friday, 25 January, 2008
Keywords: 
Primary keyword: 

B2561 - IgG antibody analysis in ALSPAC participants

B number: 
B2561
Principal applicant name: 
Robert Yolken NOTE THIS FORM WAS COMPLETED BY SUE RING |
Co-applicants: 
Title of project: 
IgG antibody analysis in ALSPAC participants
Proposal summary: 
Date proposal received: 
Wednesday, 21 October, 2015
Keywords: 

B3070 - Hypothesis driven analysis of Avon Longitudinal Study early adversity and epigenetic modulation impacting on addiction - 06/03/2018

B number: 
B3070
Principal applicant name: 
Femke Buisman-Pijlman | Adelaide Medical School, University of Adelaide (Australia)
Co-applicants: 
Associate Professor Linda Gowing, Dr Murthy Mittinty, Professor Caroline Relton, Professor George Davey Smith
Title of project: 
Hypothesis driven analysis of Avon Longitudinal Study: early adversity and epigenetic modulation impacting on addiction
Proposal summary: 

Why do people who experience early adversity have a higher chance of developing addiction? Do these experiences leave a biological scar? To answer these questions, we will use information from a group of babies, tracked since birth and who are now in their twenties. We will use new statistical methods and information on their early life, DNA and use of alcohol and tobacco as young adults, to identify which specific experiences change their biology and are linked to development of addiction.

Impact of research: 
We will both advance the statical analysis techniques that can be used to investigate causality and provide information on the relative value of specific early factors on methylation and problematic drug and alcohol use (which will be published in high ranking journals). This will provide good opportunities for assessment and early interventions.
Date proposal received: 
Saturday, 17 February, 2018
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, Birth outcomes, Epigenetics, Genetic epidemiology, Parenting, Statistical methods

B3005 - Hypertensive disorders of pregnancy and mental and behavioural disorders in offspring - 22/03/2018

B number: 
B3005
Principal applicant name: 
Rosa Alati | University of Queensland (Australia)
Co-applicants: 
Berihun Dachew, Ass. Prof Abdullah A Mamun, Dr. Kim Betts
Title of project: 
Hypertensive disorders of pregnancy and mental and behavioural disorders in offspring
Proposal summary: 

There has been increasing research attention to the impact of in utero exposures to specific perinatal risk factors and their potential impact on diseases later in life. One of these is hypertensive disorders of pregnancy (HDP), a perinatal condition which affects up to 10% of pregnancies globally. Current evidence shows that HDP are associated with an increased risk of offspring cardiovascular, immune, metabolic disorders in later life. HDP are also responsible for various adverse perinatal outcomes such as preterm birth, low birth weight and intrauterine growth restriction, which are known risk factors for numerous mental health morbidities. In addition, HDP may also affect brain development via utero-placental vascular insufficiency and fetal malnutrition and lead to subsequent neurobehavioral difficulties. A lot of research has been conducted on the associations between HDP and cognitive functioning in offspring, however, evidence on the effect of intrauterine exposure to HDP on offspring mental and behavioural disorders is not well-established.
Two systematic reviews conducted by this team, one currently under review and the other one accepted by the British Journal of Psychiatry have shown that HDP had a negative impact for a range mental or behavioural disorders. Our finding showed that preeclampsia was associated with increased risk of offspring schizophrenia. The risk of Autism spectrum disorder was also 32% higher in offspring who had intrauterine exposure to preeclampsia as compared to those non-exposed. However, we found inconclusive finding on the effect of HDP and other mental and behavioural disorders, suggesting the need of further studies to progress this area of research. Following on from these findings, this PhD project aims to add to the existing evidence in a meaningful way by conducting a high quality, large sample, birth cohort study.

Impact of research: 
This research has a potential to provide accurate information on whether there is a direct link between HDP and a range of mental and behavioural disorders in offspring. This will have potential benefits in terms of advancing the existing knowledge and help clinical decision making for interventions during pregnancy, thereby improving near and long term offspring mental health outcomes.
Date proposal received: 
Wednesday, 29 November, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Epidemiology, Hypertensive disorders of pregnancy, preeclampsia, gestational hypertension, mental disorders, behavioural disorders, offspring

B3095 - Genome-wide association analysis of voting behaviour for Mendelian randomization - 11/04/2018

B number: 
B3095
Principal applicant name: 
Neil Davies | MRC IEU
Co-applicants: 
Nic Timpson, Charlie Hatcher
Title of project: 
Genome-wide association analysis of voting behaviour for Mendelian randomization
Proposal summary: 

Genome-wide association studies (GWAS) have been critical in identifying thousands of genetic variants associated with complex traits and diseases. For certain complex traits however, it may be the case that there is difficulty in phenotypic measurement and this can lead to issues of statistical power. This is particularly problematic for behavioural phenotypes that may be predominantly determined by the environment, as is the case for educational attainment and well-being (Okbay et al., 2016; Okbay et al., 2016; Rietveld et al., 2013). Genetic analyses of such phenotypes can be hindered by the fact that individual SNPs have limited explanatory power and any associations found may not be causal or may be mediated by many other intermediate phenotypes (Krapohl et al., 2014). However, such studies have enabled the description of common genetic contributions to complex behaviours. Taken together, these GWAS results form a pool of genetic variants which may then be used in Mendelian randomization (MR) analyses; both looking at the effect of these features on outcomes but also the effect of outcomes on them.

This project will use newly collected data in the Avon Longitudinal Study of Parents and Children cohort to analyse voting behaviour. Firstly, we aim to conduct a GWAS on voting behaviour to discover any genetic variants associated with this complex trait. Additionally, we plan on considering the potential of using MR analysis to look at this behavioural phenotype. Specifically, we aim look at the effect of well instrumented risk factors on voting behaviour itself, i.e. ‘backwards MR’.

References
Krapohl, E. et al. The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence. Proc. Natl Acad. Sci. USA 111, 15273–15278 (2014).

Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses (vol 48, pg 624, 2016). Nature Genetics 48, 1591-1591 (2016).

Okbay, A. et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533, 539-+ (2016).

Rietveld, C.A. et al. GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment. Science 340, 1467-1471 (2013).

Impact of research: 
Date proposal received: 
Wednesday, 4 April, 2018
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B3114 - Tracking Sleep Phenotypes 2 15-05-2018 - 234902 - 26/05/2018

B number: 
B3114
Principal applicant name: 
Helen Heussler | Center for CHildren's Health Research. University of Qld (Australia)
Co-applicants: 
Emily Sawyer, Prof Karen Thorpe, Simon Smith , Ronny Gunnarson, Mamun Abdullah, Enda Byrne, Adam Ewing, Peter Blair
Title of project: 
Tracking Sleep Phenotypes (2) (15-05-2018 - 23:49:02)
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 patterns. Current understanding of the processes underpinning normative transition in sleep patterns, the prevalence of specific sleep phenotypes and persistence in sleep patterns across time is limited. This study will utilise genetic and environmental data, alongside longitudinal sleep data to examine the prevalence, persistence and developmental significance of childhood sleep phenotypes.

This knowledge will inform clinical, public health and educational policy and practice 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 functioning, parent well-being and child development.

Impact of research: 
The focus of our research will be important in informing care practices particularly in early childhood settings and family contexts. Internationally the importance of sleep in long term health is growing but the available evidence and subsequent evidence for policy and practice is limited. In Australia and the US for example while there are significant recommendations for exercise and nutrition in young children the existing sleep recommendations are limited to sleep safety in the first year. (We are pleased to have Prof Peter Blair on the Team) Longitudinally the existence of tight phenotypes has been challenging to establish however using this data we hope to establish some genotype- phenotype relationships to help inform practice.
Date proposal received: 
Thursday, 17 May, 2018
Keywords: 
Clinical research/clinical practice, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Mental health, DNA sequencing, GWAS, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Epigenetics, Genomics, Intelligence - memory, Sleep

B602 - EU Call - ENRIECO

B number: 
B602
Principal applicant name: 
Prof Mark Nieuwenhuijsen (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
EU Call - ENRIECO
Proposal summary: 

We are writing to all the birth cohorts in Europethat we know have an interest in environment and health to ask them to participate in this coordinating action (list attached). We have already contacted quite a number of them and leaders in various projects such as GA2LEN, ESCAPE, HIWATE and they have agreed to participate. We would like you to read the text below and let us know if you are interested in taking part in this proposal. We need an answer very soon since the deadline for submission is 25 February. Besides extracting currently available information, we also hope to generate new information (but are limited to what can be done within a coordinating action and available funding) and we have proposed a number of ideas, but other ideas are welcome. Please indicate if you are interested in any asap (and correct any incorrect information), and whether you are willing to take the lead of any of the ideas/WPs.

Date proposal received: 
Thursday, 10 January, 2008
Keywords: 
Primary keyword: 

B3071 - Parental alcohol use and offspring mental health - 06/03/2018

B number: 
B3071
Principal applicant name: 
Marcus Munafò | MRC Integrative Epidemiology Unit (UK)
Co-applicants: 
Miss Kayleigh Easey, Dr Luisa Zuccolo, Professor Nicholas Timpson
Title of project: 
Parental alcohol use and offspring mental health
Proposal summary: 

Previous research has shown detrimental offspring outcomes for children prenatally exposed to alcohol. However, uncertainty remains as to whether these negative offspring outcomes are due to the intrauterine environment, or environmental influences after birth, for example parental lifetime drinking. Further investigation is required to assess the impact of parental alcohol use on offspring outcomes. The research that has been previously conducted in this area has focused on academic outcomes, with less focus on the influence maternal and partner drinking may have on offspring mental health.
In addition, valid reports of alcohol use may be affected by under-reporting. Using parental methylation markers that are predictive of alcohol use, could be a more biologically valid method for assessing alcohol consumption. These methylation-based biomarkers were developed by Liu et al (2018) and are currently being validated by co-applicants (LZ) in ALSPAC. The proposed study will use such biomarkers to assess if this produces a stronger signal, in comparison to self-reported alcohol use.

Impact of research: 
To further inform the evidence of child mental health risks and steps that can be taken to reduce harm.
Date proposal received: 
Tuesday, 20 February, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Mental health, alcohol

B3096 - Does cognitive vulnerability modify the association between stressful life events and future depression - 11/04/2018

B number: 
B3096
Principal applicant name: 
Marcus Munafò | University of Bristol (United Kingdom)
Co-applicants: 
Miss Sarah Peters, Professor Ian Penton-Voak
Title of project: 
Does cognitive vulnerability modify the association between stressful life events and future depression?
Proposal summary: 

Several studies have found that the experience of stressful life events (ranging from more severe events, such as divorce or bereavement, to daily hassles, such as family-related obligations) can lead to symptoms of depression. However, the impact of these events varies, and not everyone who experiences a stressful event goes on to experience depression. We’re interested in studying whether cognitive vulnerability, the tendency to make negative causal inferences about an event, can explain this difference (i.e., is an effect modifier). That is, the interpretation of the event, rather than exposure to the event alone, may be particularly important for predicting future depression. This study aims to investigate how the impact of stressful events varies between people, and why certain people go on to experience depression while others do not. These findings could inform potential targets for interventions which intend to prevent depressive symptoms.

Impact of research: 
Depression is a common, costly, and life-threatening illness. Understanding the impact of factors such as cognitive vulnerability on established risk factors for depression (such as stressful life events) is relevant to both etiologic models of depression and for the development and evaluation of more targeted interventions. Quick and accessible interventions that target cognitive vulnerability may be useful for treating depression and could be informed by this research.
Date proposal received: 
Monday, 9 April, 2018
Keywords: 
Epidemiology, Mental health, Statistical methods, Mental health, depression, stressful life events, cognitive vulnerability, cognitive styles

B601 - Maternal reproductive history and the outcome of labour

B number: 
B601
Principal applicant name: 
Prof Gordon Smith (University of Cambridge, UK)
Co-applicants: 
Title of project: 
Maternal reproductive history and the outcome of labour
Proposal summary: 
Date proposal received: 
Monday, 14 January, 2008
Keywords: 
Primary keyword: 

B3072 - BIOMAP - Genome-Environment Interactions in Inflammatory Skin Disease - 06/03/2018

B number: 
B3072
Principal applicant name: 
Lavinia Paternoster | MRC IEU (United Kingdom)
Co-applicants: 
Josine Min
Title of project: 
BIOMAP - Genome-Environment Interactions in Inflammatory Skin Disease
Proposal summary: 

Atopic dermatitis (AD) and psoriasis affect a substantial percentage of the population. The mechanisms of disease, endotypes, co-morbidities of these diseases remain poorly understood. There is need to define the heterogeneous and homogeneous aspects of AD and psoriasis and identify the impact of environmental factors, genetic factors and molecular pathways. This will give rise to more precise targeted treatments. The BIOMAP project will bring together existing resources from European cohorts and industry to meet this challenge. ALSPAC, with it's rich longitudinal phenotyping and molecular data is well suited to contribute to this project.

Impact of research: 
This project aims to deliver an improved disease ontology for clinical use, with early biomarker detection of specific disease subtypes. The project also aims to better understand the molecular pathways disrupted in these subtypes, allowing for improved therapeutic treatment, targeted to the right patients. The project involves several academic and industry partners and involves patient groups, for maximal impact of the research findings.
Date proposal received: 
Tuesday, 20 February, 2018
Keywords: 
Epidemiology, Inflammatory skin disease, Statistical methods, Dermatology

B3097 - A meta-analysis of maternal smoking GFI1-CpGs and cardio-metabolic phenotypes in adults - 17/04/2018

B number: 
B3097
Principal applicant name: 
Matthew Suderman | Integrative Epidemiology Unit
Co-applicants: 
Title of project: 
A meta-analysis of maternal smoking GFI1-CpGs and cardio-metabolic phenotypes in adults
Proposal summary: 

Individuals exposed prenatally to cigarette smoke tend to have lower birthweight and have higher risks for a variety of detrimental health outcomes later in life. Cigarette smoke exposure is also associated with DNA methylation changes at gene GFI1, and recent evidence suggests that these changes may play a role in the lower birthweight of exposed infants. We would like to determine if there is evidence that these DNA methylation changes may also play a role in risk factors for other health outcomes of prenatal cigarette smoke exposure. We would specifically like to investigate factors related to cardiovascular and metabolic health.

Impact of research: 
Evidence for or against the possibility that DNA methylation mediates the effects of prenatal smoke exposure on later health outcomes.
Date proposal received: 
Thursday, 12 April, 2018
Keywords: 
Epigenetics, cardio-metabolic risk factors, Microarrays, Biological samples -e.g. blood, cell lines, saliva, etc., Birth outcomes, Blood pressure, BMI, Cardiovascular, Environment - enviromental exposure, pollution, Epigenetics, Metabolic - metabolism

B600 - Investigation of the role of bone size relative to body size in the pathogenesis of fractures in childhood

B number: 
B600
Principal applicant name: 
Dr Jon Tobias (University of Bristol, UK)
Co-applicants: 
Title of project: 
Investigation of the role of bone size relative to body size in the pathogenesis of fractures in childhood
Proposal summary: 

Aims

(i) Whether changes in bone size relative to body size contribute to the increased risk of fracture during puberty will be established, by examining the relationship between longitudinal changes in these parameters across puberty.

(ii) Whether the higher risk of fracture in pubertal boys compared to girls is related to gender differences in bone size relative to body size will be determined.

(iii) Whether small bone size relative to body size represents a stable trait that once established in childhood persists following puberty will be investigated.

Date proposal received: 
Friday, 18 January, 2008
Keywords: 
Primary keyword: 

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