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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B3465 - Genetic and Environmental Components of Parental Effects on Child Physical and Mental Health - 18/02/2020

B number: 
B3465
Principal applicant name: 
Pak C. Sham | The University of Hong Kong (Hong Kong)
Co-applicants: 
Justin Tubbs, Talia Wu, Saloni Dattani, Yiming Li, PhD
Title of project: 
Genetic and Environmental Components of Parental Effects on Child Physical and Mental Health
Proposal summary: 

Ultimately, the similarity between parents and their children can come from two sources: nature and nurture. Recently, methods have been introduced to identify the effects of “genetic nurture” - effects of the parentally-provided environment which can be explained by the parents’ genes through their influences on parental behavior (rather than through genetic transmission to their children). We have developed an extension of these methods which may allow us to find specific genetic factors which make up this effect, for nuclear families with genotype data available on at least 2 members (e.g., sibling pairs or parent-offspring pairs). This method involves imputing missing parental genotypes from the available genotypes of each nuclear family. Because of its detailed longitudinal phenotype data and genotyped mothers and children, ALSPAC is an ideal dataset to examine these effects across a number of traits important to human health and disease. The results of this study will better help us understand the important role of the parental environment in childhood development and identify specific genetic and environmental risk factors (and their interaction) for physical and mental health outcomes in children.

Impact of research: 
First, introducing and applying our novel missing genotype imputation routine and model will enhance the ability of other researchers to more fully characterize maternal and paternal effects of genetic and environmental origins across traits relevant to human health. Second, our analysis of longitudinal mental health trajectories will improve our understanding of the risk and protective factors for internalizing and externalizing disorders across development by identifying specific genetic loci and aggregate parental genetic effects, and their interaction with known risk factors.
Date proposal received: 
Friday, 7 February, 2020
Date proposal approved: 
Tuesday, 18 February, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Obesity, Computer simulations/modelling/algorithms, GWAS, Statistical methods, BMI, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Genetic epidemiology, Genome wide association study, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Parenting, Psychology - personality, Statistical methods

B3469 - Menstruation and womens health - 17/02/2020

B number: 
B3469
Principal applicant name: 
Gemma Sharp | MRC IEU, UoB
Co-applicants: 
Title of project: 
Menstruation and women's health
Proposal summary: 

There has been remarkably little research on women's experience of menstruation from a population health perspective, despite menstruation and pre-menstrual symptoms having wide-reaching consequences for women's physical and mental health. We need a better understanding of the biological (e.g. hormone levels, epigenetics) and lifestyle factors (e.g. smoking, alcohol, diet) that might predict and/or causally affect menstrual experiences (e.g. cycle length, heaviness, regularity, pain and premenstrual mood). This better understanding could inform ways to predict who is at risk of poor experiences, and develop strategies to prevent or improve those experiences. We also need a better understanding of the impact of different menstrual experiences on women's physical and mental health (e.g. fatigue, depression, life satisfaction). Again, this could inform strategies to predict which women are at risk of poor outcomes and help develop preventative interventions.

Impact of research: 
This project is one of the only projects to use quantitative data to explore menstrual experiences from a population health perspective. I therefore hope that the outputs from this project (one to two research papers) will inform better ways to predict and prevent poor menstrual experiences and associated outcomes, as well as highlighting the potential for research in this area. I plan to incorporate the results into grant applications for 1) more questions to be added to the ALSPAC questionnaires regarding menstrual health (e.g. to collect data on missing symptoms such as breast soreness and effects on the digestive system); and 2) a nested study to collect serial biological samples and questionnaire data throughout the menstrual cycle and over multiple cycles to study variation in and factors associated with menstrual symptoms between and within cycles and individuals. (If these funding applications are successful, I will put in further project proposals - and of course request funds to access ALSPAC).
Date proposal received: 
Monday, 17 February, 2020
Date proposal approved: 
Monday, 17 February, 2020
Keywords: 
Epidemiology, Women's health, Epigenome wide association study Multivariable regression, Menstruation

B3468 - Profiling the occupational and educational trajectories of individuals with special educational needs and disabilities - 17/02/2020

B number: 
B3468
Principal applicant name: 
Julia Carroll | Coventry University (United Kingdom)
Co-applicants: 
Dr Carlo Tramontano
Title of project: 
Profiling the occupational and educational trajectories of individuals with special educational needs and disabilities
Proposal summary: 

Educational and career decisions for school leavers are complex and influenced by multiple factors. These can include: factors at the level of an individual, such as cognitive abilities, motivations and self-beliefs; factors related to the family environment, such as parental education and beliefs, and family income; factors relating to the school setting, such as type of schooling; and finally factors relating to the broader economic and cultural context. These factors, besides having a direct and specific impact on individuals' educational and professional path, interact in complex ways. For individuals with special educational needs and disabilities (SEND), education and career decisions are likely to be even more complex, and we know that career advice for individuals with SEND is often patchy and incomplete.

In order to gain a thorough understanding of the factors involved in the post-secondary educational and occupational choices of individuals with SEND, we plan to combine two complementary data analysis techniques: a variable centred approach, which examines which variables play an important role in predicting outcome across the range, and a person centred approach, which is focused on a holistic analysis of the combined effect of multilevel factors. This allows us to understand whether there are different profiles of individuals with SEND who show different post-secondary choices.

Impact of research: 
There are clear ethical and economic reasons to aim that all individuals should have the opportunity to achieve their potential and find employment that is fulfilling. This in-depth approach will allow us to understand the factors that are most important in ensuring that individuals with SEND have these opportunities. It will therefore be vital in helping us understand which individuals would most benefit from support and what types of support are most beneficial.
Date proposal received: 
Thursday, 13 February, 2020
Date proposal approved: 
Monday, 17 February, 2020
Keywords: 
Social Science, Developmental disorders - autism, Cognitive impairment, Learning difficulty, Mental health, Speech/language problem, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Parenting, Psychology - personality, Statistical methods, educational outcomes; educational attainments; career choices; occupational outcomes

B3467 - SoCial Reserve as buffer against psychosis development a psychological and molecular investigation SCORE - 03/03/2020

B number: 
B3467
Principal applicant name: 
Eva Velthorst | Icahn School of Medicine at Mount Sinai (United States)
Co-applicants: 
Stanley Zammit, PhD, Hannah Jones, PhD, Avi Reichenberg, PhD, Sven Sandin, PhD, Niamh Mullins, PhD, Paul O'Reilly, PhD, Raquel Gur, PhD, Ruben Gur
Title of project: 
SoCial Reserve as buffer against psychosis development: a psychological and molecular investigation (SCORE)
Proposal summary: 

Social withdrawal (SocW) – defined as reduced social interaction – is a key feature of psychotic disorders and multiple other psychiatric outcomes. Despite growing recognition of its negative consequences, SocW remains one of the least studied human traits, and its underlying mechanisms remain subject of wide speculation. The overall goal of this project is to examine elucidate the role of SocW in the development of psychosis.

By combining clinical data with increasingly powerful ‘genetic risk scores’ (i.e. the sum of risk genes that have shown to be associated with a behavioral trait), we are now able to test whether SocW is a cause or merely a consequence of symptoms in psychosis development. Using the UK Biobank we will create a powerful genetic risk score for SocW, and use this score to examine the role of SocW in psychosis in two large developmental cohorts: The Avon Longitudinal Study of Parents and Children (ALSPAC) and Philadelphia Neurodevelopmental Cohort (PNC). Jointly, these studies followed nearly 16,000 young individuals from childhood to young adulthood, through ages encompassing typical onset of and peak onset age of psychosis. In ALSPAC, we will also test the association between changes in psychotic symptoms and changes in SocW behaviorally, and explore the effects of SocW and established environmental risk in the path to psychosis.

Overall, we aspire to better understand the well-established association between SocW and psychosis, determine critical windows during which individuals may be more or less prone to the influence of SocW, and facilitate much-needed preventive targeted therapies.

Impact of research: 
This project will fill important gaps in our knowledge about genetic underpinnings of social withdrawal, and the (causal) role of social withdrawal in pathways to psychosis, and other severe psychiatric disorders.
Date proposal received: 
Wednesday, 12 February, 2020
Date proposal approved: 
Monday, 17 February, 2020
Keywords: 
Genetics, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., GWAS, Genetic epidemiology

B3464 - Anxiety and mood disorders in young people a multivariate approach using the ALSPAC cohort - 12/02/2020

B number: 
B3464
Principal applicant name: 
Steven Marwaha | University of Birmingham
Co-applicants: 
Professor Rachel Upthegrove, Ms Daniella Asogbon
Title of project: 
Anxiety and mood disorders in young people: a multivariate approach using the ALSPAC cohort
Proposal summary: 

In this project, we will investigate the early life psychological, environmental and biological factors that may increase the risk of developing mood disorders (broadly defined) in late adolescence and early adulthood and the associated poor outcomes. Multi-factorial analyses will examine prospective impacts of diet, sleep, parental mental health, cognitive function, inflammatory markers, metabolomics and genetic susceptibility on the earliest symptoms of mood disorder.

Impact of research: 
This research will better aid the understanding of the development and presentation of anxiety and mood disorders (broadly defined) during adolescence and has the potential to aid improved early detection of these disorders for provision early and effective treatment and the prevention of secondary disease outcomes.
Date proposal received: 
Thursday, 6 February, 2020
Date proposal approved: 
Wednesday, 12 February, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3466 - Investigating maternal cannabis exposure during pregnancy and epigenetic alterations in offspring - 12/02/2020

B number: 
B3466
Principal applicant name: 
Rayjean Hung | Lunenfeld-Tanenbaum Research Institute, Sinai Health System (Canada)
Co-applicants: 
Dr. Julia Knight, Patrick O. McGowan
Title of project: 
Investigating maternal cannabis exposure during pregnancy and epigenetic alterations in offspring
Proposal summary: 

Cannabis is widely used for recreational and medical purposes with usage increasing rapidly following its legalization in parts of the world[1]. While there are well-documented effects of cannabis on the users themselves, the impact of its consumption during pregnancy on offspring is much less clear. Previous studies have reported that maternal cannabis usage during pregnancy is associated with lower birth weight and there is the suggestion of impaired neurodevelopment in both observational cohorts in humans and experimental studies in animal models[2-7]. However, how maternal cannabis exposure leads to these adverse health outcomes in offspring remains unclear.
Epigenetic mechanisms play an important role in regulating gene expression and cell homeostasis. Previous experimental studies showed that DNA methylation in offspring could be modified by maternal cannabis exposure[8-10]. In some cases this leads to dysregulation of the immune system of the fetus[11-13]. However, no human studies have yet been conducted, and no specific epigenetic signatures have been identified related to cannabis exposures. We hypothesize that maternal cannabis exposure during pregnancy alters the epigenetic profiles and leads to a specific epigenetic signature of the fetus through in utero exposure, and the epigenetic alterations can then lead to impaired neurodevelopment in the offspring. Therefore, we propose to investigate the association of maternal cannabis exposure around the time of pregnancy with DNA methylation profiles in offspring at birth in the ALSPC cohort.

Impact of research: 
With increasing prevalence of cannabis consumption in young adults, it is paramount to understand how cannabis exposures during pregnancy may affect fetal health, particularly neurodevelopment. In this study we focus on epigenetic alterations related to cannabis, which can provide insights on how cannabis exposure may impact the health outcome of next generation.
Date proposal received: 
Friday, 7 February, 2020
Date proposal approved: 
Wednesday, 12 February, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Cognitive impairment, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., epigenetics, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Offspring

B3458 - Indoor and outdoor tanning determinants in British young adults - 11/02/2020

B number: 
B3458
Principal applicant name: 
Carolina Bonilla | Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de Sao Paulo (Brazil)
Co-applicants: 
Title of project: 
Indoor and outdoor tanning determinants in British young adults
Proposal summary: 

Ultraviolet radiation (UVR) is the most important risk factor for skin cancer. Indoor tanning, defined as the use of an ultraviolet emission device to produce a cosmetic tan[1], has been associated with increased risk of melanoma and non-melanoma skin cancer (NMSC), and thus has been classified as a group I carcinogen by the International Agency for Research on Cancer[2]. Despite the risk posed by this activity, indoor tanning is common practice among young people in developed countries. A systematic review and meta-analysis of 12 studies of indoor tanning and NMSC showed that ever exposure to indoor tanning was associated with a higher risk of both, squamous cell carcinoma and basal cell carcinoma, and that exposure at a young age (< 25 years of age) increased these risks considerably[1]. Similarly, melanoma risk was significantly higher due to sunbed use, as reported by a systematic review and meta-analysis of 27 observational studies[3]. Since indoor tanning is a potentially modifiable exposure it is of interest to examine its frequency and the characteristics of its users in the ALSPAC cohort. Up until 2017 ALSPAC did not include questions regarding indoor tanning. The exceptions are the mother’s ‘Your environment’ questionnaire administered in early gestation asking how often they had used a sun bed or lamp during their pregnancy, and the child-based KN questionnaire at 69 months old asking about ever use of sun bed or lamp and its frequency. On the other hand, ALSPAC children have been assessed with respect to natural sunlight exposure at regular intervals, although only up to the age of 12 years.
In one of the last waves of data collection for ALSPAC Young People (YP, Life@25+) we requested that a number of questions regarding indoor and outdoor tanning be included. This information is now available and we would like to investigate the determinants and the effects of tanning behaviour in the participants of ALSPAC at different life stages.

References
1. Wehner, M. R.; Shive, M. L.; Chren, M.-M.; Han, J.; Qureshi, A. A.; Linos, E. Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis. Br. Med. J. 2012, 345, 1–9, doi:10.1136/bmj.e5909.
2. El Ghissassi, F.; Baan, R.; Straif, K.; Grosse, Y.; Secretan, B.; Bouvard, V.; Benbrahim-Tallaa, L.; Guha, N.; Freeman, C.; Galichet, L.; Cogliano, V.; WHO International Agency for Research on Cancer Monograph Working Group A review of human carcinogens--part D: radiation. Lancet. Oncol. 2009, 10, 751–2.
3. Boniol, M.; Autier, P.; Boyle, P.; Gandini, S. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ 2012, 345, e4757–e4757, doi:10.1136/bmj.e4757.

Impact of research: 
Uncovering determinants of indoor tanning and natural sunlight exposure habits among young people in the south of England will help us better understand the importance of these predictors as risk factors for melanoma and NMSC in this population, and might provide support for the implementation of specific preventative measures. Additionally, the influence of sun exposure on health, if identified, will lead us to consider sunlight-related interventions in order to improve the population’s wellbeing.
Date proposal received: 
Tuesday, 4 February, 2020
Date proposal approved: 
Tuesday, 11 February, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, GWAS, Statistical methods, sun exposure

B3463 - Understanding the life course trajectories of adolescents who report psychotic and affective symptoms - 05/02/2020

B number: 
B3463
Principal applicant name: 
Stephen Puntis | University of Oxford (England)
Co-applicants: 
Professor Belinda Lennox
Title of project: 
Understanding the life course trajectories of adolescents who report psychotic and affective symptoms
Proposal summary: 

Mental illness most frequently emerges during adolescence and early adulthood in both psychotic and affective mental illnesses. This developmental period of the life course is one with a vast amount of biological, social and psychological change, during which young people move from early school education to further education and employment. The onset of mental illness during this important period can interrupt this development (Yung et al, 2012).

There is a large body of evidence investigating the relationship between mental ill health and educational achievement and work-related disability (Marwaha et al, 2007; Hale et al., 2015). Most studies investigating this relationship focus on either cross-sectional comparisons, or test longitudinal repeated measures data against end-point relationships (e.g. a binary in work or not in work endpoint). Few explore the heterogeneity of these trajectories over time.

In this study, we aim to measure how differences in education and employment in people with and without psychotic experiences and depressive symptoms emerge over time. To do this, we will use sequence analysis, which is a statistical technique used to identify common patterns in sequences or states over time, aiding in the identification of common life course trajectories. Distinguishing typical and atypical education and employment trajectories over time could give us insight into how this developmental period differs in those with and without psychotic and depressive symptoms. It could also identify where, and at what point in time, interventions could be delivered to reduce these differences.

Impact of research: 
There are two primary focuses for mental illness - prevention and treatment. This study will contribute to both. A better understanding of the early lifecourse education and employment trajectories of people who experience poor mental health will allow us to both better understand where and 'when' these differences are, and to target specific ages where the differences in education and employment start to emerge.
Date proposal received: 
Wednesday, 5 February, 2020
Date proposal approved: 
Wednesday, 5 February, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Mental health

B3462 - INFLUENCE OF EARLY-LIFE PET EXPOSURES ON THE RISK OF ALLERGIC SENSITISATION AND ASTHMA IN CHILDHOOD - 03/03/2020

B number: 
B3462
Principal applicant name: 
Angela Pinot de Moira | University of Copenhagen (Denmark )
Co-applicants: 
Title of project: 
INFLUENCE OF EARLY-LIFE PET EXPOSURES ON THE RISK OF ALLERGIC SENSITISATION AND ASTHMA IN CHILDHOOD
Proposal summary: 

Studies investigating the influence of early-life pet exposures on the risk of childhood asthma have been inconsistent: some studies have observed a decreased risk whilst others have observed no effect or even an increased risk of asthma following early-life pet exposure. This study aims to use data from several longitudinal studies to investigate how exposure to pets during pregnancy or early-life influences the likelihood of: a) the immune system recognising allergens (allergic sensitisation); b) developing asthma. The study will also investigated the relative influence of type (dogs vs. cats), timing (pregnancy, early life, never) and degree (number) of pet exposures on allergic sensitisation and asthma.

Impact of research: 
Results will further our understanding of the aetiology of asthma, highlight possible intervention strategies to reduce asthma incidence and severity, and help create more  effective guidelines regarding animal exposures during pregnancy and early-life
Date proposal received: 
Tuesday, 4 February, 2020
Date proposal approved: 
Wednesday, 5 February, 2020
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, Pets

B3455 - Cardiorespiratory fitness adiposity and lean mass in relation to arterial structure and function from childhood to adulthood - 03/02/2020

B number: 
B3455
Principal applicant name: 
Prof. Tomi-Pekka Tuomainen | University of Eastern Finland (Finland)
Co-applicants: 
Dr. Andrew O. Agbaje, Dr. Alan R. Barker
Title of project: 
Cardiorespiratory fitness, adiposity, and lean mass in relation to arterial structure and function from childhood to adulthood
Proposal summary: 

Cardiovascular disease, a frontline cause of death worldwide, has some risk factors such as obesity, poor cardiorespiratory fitness (CRF), and vascular dysfunction whose primordial signs exist in childhood. Evidence suggests that excess body fat and poor CRF predict increased cardiometabolic risk and the progression of atherosclerosis. However, the mechanisms underlying vascular dysfunction with respect to predictors such as CRF, body fat, and lean mass in the young remains poorly understood.

It is unclear whether CRF in childhood and adolescence impact arterial structure and function in later life. Although several studies have assessed the influence of childhood CRF on early and or later arterial health, they are either of cross-sectional or short-term longitudinal design. Most of these studies have focused on a specific period (e.g. early or late childhood) and are restricted to a one-time measure of CRF. Moreover, inappropriate scaling measure of CRF such as not accounting for the confounding effect of body fat makes interpretation of existing evidence difficult.

Similarly, accumulation of body fat and lean mass during childhood through adolescence may significantly impact arterial health in early adulthood. But, studies that describe the physiological adaptation of vascular structure through adolescence to young adulthood in relation to increased body fat and lean mass are few. A repeated measure of CRF, body fat and lean mass is essential to determining critical periods of early life during which these factors implicate later arterial health. Evidence on suitable target ages for cardiovascular intervention, alongside unraveling the cryptic mechanisms by which CRF, body fat and lean mass relate to arterial health could be achieved. We would, therefore, assess the importance of early life exposures (e.g. CRF, body fat, lean mass, and/or endothelial function) from childhood through adolescence on vascular phenotypes between ages 9 to 24.

Impact of research: 
We aim to publish our findings in international peer-reviewed journals and also disseminate press releases to the general public via news channels. To provide scientific evidence on possible age-specific interventions that could mitigate the sub-clinical progress of arterial diseases from childhood.
Date proposal received: 
Thursday, 30 January, 2020
Date proposal approved: 
Monday, 3 February, 2020
Keywords: 
Paediatric Exercise Medicine/Physiology and Epidemiology, Hypertension, Obesity, Atherosclerosis, myocardial infarction, cardiovascular disease, metabolic disorders, Statistical methods, Allometric scaling, mixed-method, Biological samples -e.g. blood, cell lines, saliva, etc., Blood pressure, BMI, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Physical - activity, fitness, function, Puberty, Sex differences, Statistical methods, Cardiorespiratory fitness, endothelial function, metabolic health, carotid intima-media thickness, arterial distensibility, obesity, fat-free mass, fat mass, cardiovascular health, arterial stiffness, childhood, adolescence, early adulthood, atherosclerosis, cardiovascular diseases, public health.

B3459 - Is the association between maternal pre-pregnancy BMI and breastfeeding outcome mediated by changes in maternal DNA methylation - 03/02/2020

B number: 
B3459
Principal applicant name: 
Sinead English | School of Biological Sciences (United Kingdom)
Co-applicants: 
Dr Doretta Caramaschi, Ms Chloe Bennett
Title of project: 
Is the association between maternal pre-pregnancy BMI and breastfeeding outcome mediated by changes in maternal DNA methylation?
Proposal summary: 

Previous research has shown that maternal BMI (body mass index) is associated with reduced breastfeeding. Several studies have shown that increased maternal BMI can affect biological processes such as lactogenesis and that societal factors surrounding increased maternal BMI such as low body confidence can affect breastfeeding. Less is known, however, about any underlying genetic or epigenetic associations between maternal BMI and breastfeeding outcome. We ask to what extent the relationship between maternal BMI and breastfeeding outcome is mediated by changes in the mother’s epigenome, whether any differentially expressed genetic regions are associated with appetite or weight regulation, and how stable these epigenetic associations are across time.

Impact of research: 
Obesity rates in the UK are increasing and having a profound effect on the health and wellbeing of the population. Breastfeeding provides a range of benefits to a growing child that continue into adulthood. It is important to better understand the underlying association between maternal obesity and reduction in breastfeeding initiation and duration to increase breastfeeding rates in the UK. If biological mechanisms behind reduced breastfeeding are better understood, then relevant health incentives can be targeted towards susceptible groups within the population.
Date proposal received: 
Monday, 3 February, 2020
Date proposal approved: 
Monday, 3 February, 2020
Keywords: 
Epidemiology, Diabetes, Statistical methods, BMI, Breast feeding, Epigenetics

B3460 - The power of the environment Environmental mediation of genetic liability - 03/02/2020

B number: 
B3460
Principal applicant name: 
Moritz Herle | Kings College London (UK)
Co-applicants: 
Prof Andrew Pickles, Prof Bianca De Stavola
Title of project: 
The power of the environment: Environmental mediation of genetic liability
Proposal summary: 

The consequences of childhood obesity remain one of the biggest public health burdens in the UK. 1 in 3 children are already overweight or obese by age 10 years. This is especially problematic because obesity has been linked to many health conditions, such as diabetes, cancer and depression. There is now substantive evidence that obesity runs in families, but genetics alone cannot explain the current rise of obesity in the population. So environmental factors have been proposed to be causal for this development. It is this dual determination, that remains paradoxical:
How is it possible that obesity is explained by both genes and environments and what does this complexity mean for public health interventions?
For childhood obesity, we already know that genetic and environmental factors are
important. However, it is not known how environmental factors might be protective of genetic
liability.
The main questions are:
1. Do parental feeding practices, such as offering food to soothe, enhance or buffer the
association between genetic liability and later childhood BMI, and what could be
achieved if we changed parental feeding strategies?
2. Does the child’s physical activity mediate the association between childhood genetic
liability and later BMI, and what would happen if levels of physical activity increased?
3. Can maternal genetic risk influence the child’s body size, even though the genetic liability
are not passed on?
4. What is the association between genetic liability and the built environment of the family
home, such as access to green spaces and public transport?

Impact of research: 
The proposed research is timely, and of great public interest. Polygenic scores for common disease are increasingly available through commercial providers. However, their association with environmental factors is not fully understood. This project brings together methods form genetic epidemiology and mediation analysis, highlighting a novel way to address complex questions, which can be adopted by other health researchers.
Date proposal received: 
Monday, 3 February, 2020
Date proposal approved: 
Monday, 3 February, 2020
Keywords: 
Epidemiology, Obesity, Statistical methods, BMI, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Genetic epidemiology, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Parenting, Physical - activity, fitness, function, Statistical methods

B3451 - Markers of infection within Twins - - 28/01/2020

B number: 
B3451
Principal applicant name: 
Fergus Hamilton | MRC IEU / North Bristol NHS Trust / PHS (Avon)
Co-applicants: 
Ruth Mitchell, Nic Timpson
Title of project: 
Markers of infection within Twins -
Proposal summary: 
Impact of research: 
1. Publications in peer-reviwewed journals 2. Grant application to TwinsUK to perform serology within their (much larger!) cohort of Twins 3. A greater understanding of how infection works, and how heritable it is.
Date proposal received: 
Thursday, 23 January, 2020
Date proposal approved: 
Tuesday, 28 January, 2020
Keywords: 
Immunology, Infection, Classic Twin Study., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Twins

B3452 - Physical activity and prediabetes in adolescents and young adults - 28/01/2020

B number: 
B3452
Principal applicant name: 
Soyang Kwon | Ann & Robert H Lurie Children's Hospital of Chicago (USA)
Co-applicants: 
Title of project: 
Physical activity and prediabetes in adolescents and young adults
Proposal summary: 

This proposed project is to examine whether inactive youth are more likely to have prediabetes in adolescents and young adults.

Impact of research: 
A recent U.S. surveillance data revealed that 18% of adolescents and 24 % of young adults are pre-diabetic, which is alarming in public health. The likely impact of this research will be to provide direct evidence to support that an active lifestyle can prevent prediabetes in youth and young adults.
Date proposal received: 
Thursday, 23 January, 2020
Date proposal approved: 
Tuesday, 28 January, 2020
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Diabetes, Biological samples -e.g. blood, cell lines, saliva, etc., Physical - activity, fitness, function

B3453 - Exploring candidate gene mechanisms in atopic eczema - 28/01/2020

B number: 
B3453
Principal applicant name: 
Sara Brown | University of Dundee (UK)
Co-applicants: 
Dr Lavinia Paternoster
Title of project: 
Exploring candidate gene mechanisms in atopic eczema
Proposal summary: 

Eczema is an itchy skin condition that is caused by a combination of genetics – our DNA – and environmental effects, eg allergens and irritants. Eczema and other allergic conditions often run in families, showing that the effects of our DNA are important, but we are not sure which specific genes are responsible for causing eczema. If we could understand genetic mechanisms we may be able to use this knowledge to develop better treatments.
Studies carried out in large populations (including ALSPAC participants) have shown which regions of DNA may contribute to causing eczema. We have tested these regions in the lab and shown, using skin samples grown in an incubator, that genes which are switched on or off in skin can cause eczema or protect against eczema. We now need to explore whether these findings are important in childhood, comparing children with and without eczema. We would like to do this using the results of analyses from blood and skin samples collected in ALSPAC.
We hope that the results of our work will give valuable clues to how an individual’s DNA contributes to their risk of suffering from eczema.

Impact of research: 
The main aim is to identify molecular mechanisms which may be targetable for eczema therapy – to bring about much needed improvements in the treatment of this disease. If we are not successful in identifying targetable mechanisms, the findings will still be of fundamental scientific value.
Date proposal received: 
Thursday, 23 January, 2020
Date proposal approved: 
Tuesday, 28 January, 2020
Keywords: 
Genetics, Allergy, Eczema, DNA sequencing, RNA, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Dermatology, Epigenetics, Genetic epidemiology, Genetics

B3456 - Exploring causal effects of health behaviours on mental health and wellbeing - 28/01/2020

B number: 
B3456
Principal applicant name: 
Robyn Wootton | MRC IEU and School of Psychological Science
Co-applicants: 
Dr Hannah Sallis, Dr Adele Wang
Title of project: 
Exploring causal effects of health behaviours on mental health and wellbeing
Proposal summary: 

Poor mental health affects all domains of life, including work, relationships and physical health. Prevalence of mental illness in the UK is increasing, with 1 in 6 people experiencing mental health problems each week. One way of tackling this mental illness epidemic is through prevention. We can achieve this by maintaining and improving people's general mental health and wellbeing, before they reach a clinical diagnosis of mental illness. In this project we are interested in identifying behaviours in ones life that can be modified to improve mental health and wellbeing.

One possible predictor of mental health is our health behaviours. For example, our diet, how much physical activity we do, how much alcohol we consume and whether or not we smoke. While this may seem intuitive, there are many gaps in the research literature. First, it is commonly thought that these behaviours influence our mental health and wellbeing, but little research has been done to assess whether this is a causal effect rather than just a correlation. In order to identify effective intervention targets, it is critically important to ensure that these are causal. We will use complementary methods, allowing us to approach our research question through a number of different lenses. If we can draw consistent results, then we will be able to obtain the strongest and most informative evidence. Second, there is little research that has looked at the nuances of these health behaviours. For example, does the length or intensity of physical activity matter when considering its effect on mental health? We will use the wealth of secondary data available to us to untangle these specific details. Third, these health behaviours do not occur in isolation, therefore, we will investigate how they work together to affect
mental health. And finally, early intervention (i.e. in childhood) is an important aspect of prevention. We will use novel methods to understand how parental health behaviours influence the child's mental health. This can inform us about whether it is better to intervene on the parents or on the child's health behaviours.

Impact of research: 
Date proposal received: 
Monday, 27 January, 2020
Date proposal approved: 
Tuesday, 28 January, 2020
Keywords: 
Epidemiology, Mental health, Statistical methods, Mendelian randomisation

B3457 - The association between traumatic brain injury and emotion recognition - 28/01/2020

B number: 
B3457
Principal applicant name: 
Robyn Wootton | School of Psychological Science and MRC IEU
Co-applicants: 
Maren Muller-Glodde, Professor Ian Penton-Voak, Professor Marcus Munafo
Title of project: 
The association between traumatic brain injury and emotion recognition
Proposal summary: 

It is relatively well established that having a traumatic brain injury is associated with subsequent deficits in emotion recognition from facial expressions (Babbage et al., 2011) and these deficits are thought to be relatively stable over time (Ietswaart, Milders, Crawford, Currie, & Scott, 2008). Changes in emotion recognition do not seem to be limited to people with moderate or severe injuries (Ietswaart et al., 2008; Kubu, 1999; Kubu et al., 1993), although there has been little research on specifically mTBI in this field. Léveillé, Guay, Blais, Scherzer, and De Beaumont (2017) after multiple concussion injuries suggested that males but not females show impaired emotion recognition. Further mood disorders, such as anxiety (Attwood et al., 2017) and depression (Dalili, Penton-Voak, Harmer, & Munafo, 2015) have been shown to impact emotion recognition. The aim of the current study is to investigate the effect of mTBI on emotion recognition in ALSPAC, whilst exploring the potential impact of factors such as sex, general cognitive ability, and mood.

Impact of research: 
Date proposal received: 
Monday, 27 January, 2020
Date proposal approved: 
Tuesday, 28 January, 2020
Keywords: 
Epidemiology, mild traumatic brain injury, Statistical methods, Cognition - cognitive function

B3454 - Exploring the effects of twin birth and prematurity on school readiness and early academic outcomes - 04/02/2020

B number: 
B3454
Principal applicant name: 
Amy Atkinson | Born in Bradford, Bradford Institute for Health Research (West Yorkshire)
Co-applicants: 
Professor Mark Mon-Williams, Dr Liam Hill, Dr Katherine Pettinger
Title of project: 
Exploring the effects of twin birth and prematurity on school readiness and early academic outcomes
Proposal summary: 

The project will explore how being born as part of a twin birth or being born premature affects school readiness (performance on entry assessments) and academic outcomes during the early primary school years (Key Stage 1).

There is evidence that twins have poorer academic outcomes during early adulthood relative to singletons (Tsou, Tsou, Wu, & Liu, 2008). It is possible that this is actually a consequence of the increased probability of twins being born preterm or small for gestational age.
In addition, this finding is not consistently observed; a large scale Danish study found no significant differenes in adolescents’ academic outcomes between twins and singletons (Christensen, Petersen, Skytthe, & Hersking, 2006). We aim to explore whether being born as a twin affects school readiness and early academic outcomes relative to being an only child or having one older non-twin sibling and if so, whether this effect persists after controlling for factors known to affect academic outcomes (e.g. birth weight, maternal education).

The second research question aims to examine whether the birth order of twins affects academic outcomes. There is some evidence that first born twins weigh more than second born twins (Yokoyama et al., 2016). Whilst first born twins can be delivered in much the same way as a singleton, there are many more opportunities for obstetric complications (and therefore perinatal compromise) for second born twins, particularly if delivered vaginally. Intrapartum monitoring of the second twin can be challenging, there may be a malpresentation of the second twin requiring internal cephalic version and breech delivery; if these manouveres fail an emergency caesarean section may be required (Leung 2002, Leung 2004). The analysis will therefore explore whether first born twins perform better academically during the primary school years, and whether this effect differs depending on the mode of delivery. Also of interest is whether any effects are reduced or eliminated once controlling for factors such as birth weight and gestational age.

A final analysis will be completed to explore whether children born preterm have worse academic performace relative to their term born siblings. Pettinger et al. (2019) found that gestational age was a significant predictor of whether a child attained a good level of development on the early years foundation stage profile (EYFSP) (e.g. Pettinger et al., 2019). The EYFSP is a mandatory assessment carried out in all state-funded schools at the end of reception year, and is seen as a measure of ‘school readiness’.
However, it is possible that this effect may be (in part) explained by the home environment. Although Pettinger et al. (2019) controlled for factors such as maternal education and receipt of means tested benefits, there may be other unknown environmental factors that affect school readiness. Comparing preterm children to term born siblings would allow us to control for these factors. There is published evidence from Scandinavian studies using sibling matching, which shows that extreme prematurity (<27 weeks gestation) is associated with increased mortality, autism and low educational attainment (D’Onofrio BM, 2013; Risnes KR, 2016). Our work could add significantly more than this, since this study only reported on ‘years in education’ and ‘failing’ education.

These analyses have been completed on the Born in Bradford data already (approval code: SP335). However, the number of children in each analysis is small, limiting the conclusions that can be drawn. We are therefore seeking to replicate our findings using the ALSPAC database, as this would allow us to strengthen our conclusions if the outcomes are replicated. If possible, we also plan to run a set of analyses on a combined dataset, which would allow us to increase the statistical power.

Impact of research: 
Date proposal received: 
Friday, 24 January, 2020
Date proposal approved: 
Friday, 24 January, 2020
Keywords: 
Social Science, Statistical methods, Childhood - childcare, childhood adversity, Development, Offspring, Siblings, Twins

B3450 - Predicting comprehensive smoking behaviours using epigenetic risk scores - 24/01/2020

B number: 
B3450
Principal applicant name: 
Ryan Langdon | ICEP (UK)
Co-applicants: 
Dr Matthew Suderman, Dr Paul Yousefi, Dr Rebecca Richmond
Title of project: 
Predicting comprehensive smoking behaviours using epigenetic risk scores
Proposal summary: 

The negative health risks of exposure to cigarette smoke are well known; including personal, second-hand and foetal exposure during pregnancy.
These health risks, in addition to a high prevalence in the UK and worldwide, make accurate measurement of smoking status an important factor in most epidemiological studies.

DNA methylation appears to provide reliable and long-term markers of tobacco smoke exposure. In fact, it is possible to use combinations of methylation levels at smoking-associated CpG sites to not only differentiate among current, former and never smokers but to also detect smoking intensity, number of smoking years and time since cessation. These aspects of smoking aren't necessarily captured in questionnaire-based responses for a given study. Even if they were, they might not be reliable and may even be misreported. For example, saying you smoke 20 cigarettes a day doesn't say how deep you inhale those cigarettes or whether the brand matters. Moreover, you might be a current smoker but say you're not a smoker out of guilt. Methylation provides a continuous measure (0-100%) in response to various aspects of smoking (rather than "yes/no"), and objectively shows a response to smoking, so can overcome these issues.

Recently, a study by Leffondre found a comprehensive measure of smoking history that incorporated intensity, duration, and time since cessation (including the half-life of the effect of stopping smoking). We will use ARIES DNA methylation data to develop predictors of smoking behaviour using this index, which we will compare against self-reported smoking behaviour from questionnaires and ALSPAC cotinine data. We hope to derive a comprehensive prediction model of smoking which can be applied to other cohorts. Methylation may be able to be used in the absence of self-report data, or more importantly, help improve prediction of diseases which are caused by smoking.

Impact of research: 
This research aims to investigate the efficacy of using DNA methylation as an objective biomarker for comprehensive smoking history, potentially being used as tool for estimating the extent of misreporting in self-reported smoking behaviours and, to a greater extent, to be used to improve prediction of smoking-related adverse health outcomes where methylation data is available.
Date proposal received: 
Wednesday, 22 January, 2020
Date proposal approved: 
Wednesday, 22 January, 2020
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics, Fathers, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Offspring, Statistical methods

B3449 - Moving from self-harm or violence towards others to dual harm predictors of transition in early adulthood - 21/01/2020

B number: 
B3449
Principal applicant name: 
Sarah Steeg | University of Manchester
Co-applicants: 
Dr Peter Taylor
Title of project: 
Moving from self-harm or violence towards others to dual harm: predictors of transition in early adulthood
Proposal summary: 

‘Dual harm’ is a term that has been used to describe the co-occurrence of self-harm and violence to others. Young people engaging in dual harm are likely to have specific clinical and support needs. However, very little is known about their characteristics and how individuals who have dual harmed differ from those who self-harm and those who are violent. Understanding the characteristics of people with dual harm experiences will help design services to meet their needs.
We will use data from the ALSPAC to look at differences between young people reporting self-harm, violence towards others, dual harm and neither behaviours at age 16. We are interested in differences in depression, attitudes towards violence, being exposed to self-harm and violence in the home or among peers, impulsivity, self-esteem, callous-unemotional traits, behavioural and emotional dysregulation and body image. We will then look at young people who report either self-harm or violence at age 16 and go on to report dual harm in young adulthood. We expect that their characteristics will differ from those who do not transition to dual harm.

Impact of research: 
Young people engaging in dual harm have particularly raised risks of premature mortality (3) and higher rates of psychiatric disorder (1). While there has been extensive research into characteristics and risk factors among young people who have self-harmed, very little is known about young people who move from engaging in self-harm or violence towards others to dual harm. The findings of this study will help shed light on this highly vulnerable population. Understanding the distinct characteristics of this group is the first step in developing appropriate support and clinical interventions. Reference list 1. Richmond-Rakerd LS, Caspi A, Arseneault L, et al. Adolescents Who Self-Harm and Commit Violent Crime: Testing Early-Life Predictors of Dual Harm in a Longitudinal Cohort Study. The American journal of psychiatry 2019: appiajp201818060740-appiajp. 2. Mars B, Heron J, Klonsky ED, et al. What distinguishes adolescents with suicidal thoughts from those who have attempted suicide? A population-based birth cohort study. Journal of Child Psychology and Psychiatry 2019; 60(1): 91-9. 3. Steeg S, Webb RT, Mok PLH, et al. Risk of dying unnaturally among people aged 15-35 years who have harmed themselves and inflicted violence on others: a national nested case-control study. Lancet Public Health 2019; 4(5): E220-E8. 4. Slade K. Dual harm: the importance of recognising the duality of self-harm and violence in forensic populations. Medicine Science and the Law 2019; 59(2): 75-7. 5. Mars B, Heron J, Crane C, et al. Clinical and social outcomes of adolescent self harm: population based birth cohort study. Bmj-British Medical Journal 2014; 349: G5954-G. 6. Latzman R.D, Lilienfeld S.O, Latzman N.E, Clark L.A. Exploring Callous and Unemotional Traits in Youth via General Personality Traits: an Eye Towards DSM-5. Personality Disorders: Theory, Research, and Treatment 2013; 4(3): 191-202.
Date proposal received: 
Monday, 20 January, 2020
Date proposal approved: 
Tuesday, 21 January, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Violence, Statistical methods, Psychology - personality

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