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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B4436 - Epigenetic markers of gender domains distinct from biological sex - 27/10/2023

B number: 
B4436
Principal applicant name: 
Julian Christians | Simon Fraser University (Canada)
Co-applicants: 
Dr. Wendy Robinson, Dr. Julia Smith
Title of project: 
Epigenetic markers of gender domains, distinct from biological sex
Proposal summary: 

Sex and gender must be taken into account in health research and the provision of care. While sex refers to biological differences and gender refers to sociocultural effects, these terms are often used interchangeably, and most studies only consider their combined effects in a binary framework comparing two sexes/genders. We aim to develop a tool to distinguish gender from sex using epigenetic markers (chemical alterations to DNA that can be readily measured in biological samples such as blood). This will enable researchers and health care providers to go beyond simply dividing into two groups by sex (male vs female), and will recognize a continuum of masculinity and femininity, relevant to both cis and trans individuals. This tool will improve research into the social determinants of health, and help to tailor health care decisions and interventions to individuals.

Impact of research: 
This research defies paradigms by considering the potential imprint of gender on biology, and by viewing gender as non-binary and made up of multiple domains. The ability to distinguish between biological sex and sociocultural gender would revolutionize health research and clinical practice by allowing us to move beyond a binary view of gender completely confounded by sex. Our index could be used for retrospective samples, where blood samples may be available, but gender-related variables are not. Prospectively, blood samples may be less invasive than surveys for study participants, and less labour-intensive to collect, making it easier to incorporate both sex and gender and to consider multiple dimensions of gender in studies. This in turn would improve understanding of the social determinants of health, identify factors likely to generalize between populations and improve care of gender-diverse people.
Date proposal received: 
Friday, 13 October, 2023
Date proposal approved: 
Friday, 27 October, 2023
Keywords: 
Epidemiology, The present study will not examine specific diseases/ conditions, but rather will develop a tool that can be used to examine the relative contributions of sex and gender to a variety of aspects of health (in future work)., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Sex differences, Gender differences

B4442 - Genetic variation and alcohol use and smoking - contribution to GSCAN GWAS Sequencing Consortium of Alcohol and Nicotine use - 27/10/2023

B number: 
B4442
Principal applicant name: 
Jasmine Khouja | University of Bristol (United Kingdom)
Co-applicants: 
Prof Marcus Munafo
Title of project: 
Genetic variation and alcohol use and smoking - contribution to GSCAN GWAS Sequencing Consortium of Alcohol and Nicotine use
Proposal summary: 

In this study, we will be exploring the relationship between genetics and smoking and alcohol use. We will combine the findings with findings from other studies around the world. We will also explore whether our environment (based on year of birth) can impact this relationship.

Impact of research: 
An impactful publication which will facilitate further analyses such as Mendelian randomisation studies. Previous versions have been cited over 800 times.
Date proposal received: 
Saturday, 21 October, 2023
Date proposal approved: 
Friday, 27 October, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, Genome wide association study

B4435 - Understanding the aetiology of Childhood self-harm in the general population An epidemiological approach - 30/10/2023

B number: 
B4435
Principal applicant name: 
Robyn Wootton | University of Bristol, and Lovisenberg Hospital
Co-applicants: 
Anastasia Izotova
Title of project: 
Understanding the aetiology of Childhood self-harm in the general population: An epidemiological approach
Proposal summary: 

The prevalence of self-harm in young people is increasing whilst the age of self-harm onset is decreasing. Prevention and early identification of self-harm is critical to prevent additional adverse outcomes. The majority of research to date has focused on self-harm during adolescence and adulthood. Little is known about the prevalence of childhood self-harm in the general population, its risk factors, and likely outcomes. The CHARM project is uniquely positioned to answer these questions, with data on self-harm behaviours in children as young as three and longitudinally up to age 16 years. This is combined with a wealth of longitudinal data including questionnaires, linkage to national health registries, genetic data, parent data and detailed environmental exposure data. The CHARM project will leverage this amazing resource to build the most detailed picture to date of emergence, persistence and aetiology of childhood self-harm in the general population. Furthermore, we will apply genetic epidemiology techniques to strengthen causal inference, which increases the likelihood of interventions being effective. Together, these analyses will paint a rich picture of an understudied phenotype and help inform intervention design to prevent childhood self-harm and consequently prevent later adverse outcomes.

Impact of research: 
Date proposal received: 
Tuesday, 10 October, 2023
Date proposal approved: 
Tuesday, 24 October, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity

B4443 - An examination of the association between school absence and exclusion and violent crime - 09/11/2023

B number: 
B4443
Principal applicant name: 
Alison Teyhan | University of Bristol
Co-applicants: 
Rosie Cornish, Iain Brennan, Jasmine Rollings
Title of project: 
An examination of the association between school absence and exclusion and violent crime
Proposal summary: 

Understanding the relationship between absence from school – unenforced, in the form of absence, or enforced, in the form of suspension or exclusion – and violence is a pressing issue. There are strong beliefs among some policy-makers and researchers that exclusions, in particular, are a direct cause of later offending and, on this basis, some school areas have moved to prohibit exclusions. While there are many harms associated with absence or exclusion, misconstruing the nature of the link between them and violence risks stigmatising those children and distracting attention from the underlying causes of violence. We seek to estimate the absence/exclusion-violence connections in a way that will inform school policies and guide the timing and context of violence prevention programmes for the future.

Impact of research: 
There is currently a lack of evidence as to whether the observed relationship between violent offending and exclusion and absence from school is causal. The aim is that our study will contribute to the evidence base on whether interventions to improve school attendance/reduce exclusion are likely to reduce youth violence.
Date proposal received: 
Monday, 23 October, 2023
Date proposal approved: 
Tuesday, 24 October, 2023
Keywords: 
Criminology Violence Education, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Computer simulations/modelling/algorithms, Childhood - childcare, childhood adversity, Education, school absence, school exclusion, crime, violence

B4432 - The Impact of Adverse Childhood Experiences on Autonomic Functioning Across the Lifecourse - 23/10/2023

B number: 
B4432
Principal applicant name: 
Yvonne Kelly | University College London
Co-applicants: 
Mrs Sidonie Kilpatrick, Dr Rebecca Lacey
Title of project: 
The Impact of Adverse Childhood Experiences on Autonomic Functioning Across the Lifecourse
Proposal summary: 

In the past 25 years, studies like the Welsh Adverse Childhood Experiences and Resiliency Survey (Public Health Whales 2018) and a representative British household survey (Bellis et al. 2014) have revealed that adverse childhood experiences (ACEs), such as abuse and neglect, are very common. They have highlighted an unfortunate truth that around 50% of children in England and Wales have experienced at least one form of adversity in childhood (Public Health Whales 2018, Bellis et al., 2014).

Traditionally, researchers have measured ACEs by summing up the total number of adversities experienced (cumulative risk models) across childhood and adolescence. Additionally, researchers have stressed the importance of investigating the individual impact of specific adversities, called specificity models. Both methods, however, have their weaknesses. Cumulative risk models do not account for the child’s experiences, and the duration and the timing of the experience. Conversely, examining individual adversities ignores the co-occurrence of these experiences and allows the relationship to potentially be confounded by other adversities.

In recent years, researchers such as Ellis and colleagues (2022) have introduced a new, comprehensive method to assess environmental adversity, known as dimensional models. A dimensional approach to measuring and classifying ACEs is a powerful tool as it recognises and evaluates a wide spectrum of negative experiences that differ in severity and timing. This enables researchers to delve into the ways and reasons by which negative environmental experiences affect developmental processes.

ACEs have been linked to many adverse cardiovascular health outcomes in every stage of the life span. In childhood 4 or more ACEs have been linked to increased resting heart rate (HR) in late childhood (12-14 years) (Petty et al., 2013) and enlarged arterial stiffness from childhood to young adulthood over time (Rafiq et al., 2020). Adults who experience a larger number and a greater impact to adverse life events in childhood demonstrated higher HR reactivity in response to an acute psychological stressor, indicating that life events are associated with elevated HR and reduced HR complexity in response to acute stress (Schneider et al., 2021). Moreover, these results indicate that poor cardiovascular outcomes appear earlier than expected in late childhood and early adolescence, stressing the importance of early intervention.

The connection between ACEs and cardiovascular health is not consistent because of the heterogeneity in ACEs definitions and study populations (Wesarg et al., 2022). To gain better insights into how a child’s unique vulnerability to adversity is mediated by individual characteristics, such as family factors, extrafamilial conditions, personality, or temperament (Belsky et al., 2013), a life course approach using birth cohort data is needed.

Sidonie Kilpatrick’s PhD dissertation investigates how ACEs impact heart-related automatic functions (i.e., autonomic functioning) throughout an individual’s life and identifies factors that can mitigate this impact. She will use data from two studies, the 1946 National Survey of Health and Development (NSHD) and the Avon Longitudinal Study of Parents and Children (ALSPAC), that collect information from the prenatal period to death. She plans to evaluate how ACEs influence resting blood pressure and heart rate across the life span and midlife heart rate variability. Additionally, she plans to evaluate how specific characteristics or interventions can influence resting HR and BP across the life course to better inform early intervention and policy.

References:
Bellis M A, Hughes K, Lechenby N, et al., . National household survey of adverse childhood experiences and their relationship with resilience to health-harming behaviors in England. BMC Med. 2014; 72(12): https://doi.org/10.1186/1741-7015-12-72

Belsky J, Pluess M. Beyond risk, resilience, and dysregulation: phenotypic plasticity and human development. Dev Psychopathol. 2013 Nov;25(4 Pt 2):1243–61.

Ellis BJ, Sheridan MA, Belsky J, McLaughlin KA. Why and how does early adversity influence development? Toward an integrated model of dimensions of environmental experience. Dev Psychopathol. 2022 May;34(2):447–71.

Pretty C, O’Leary DD, Cairney J, Wade TJ. Adverse childhood experiences and the cardiovascular health of children: a cross-sectional study. BMC Pediatr. 2013 Dec 17;13:208.

Public Health Whales, Sources of resilience and their moderating relationships with harms from adverse childhood experiences. Public Health Whales. 2018; https
://www.wales.nhs.uk/sitesplus/documents/888/ACE%20&%20Resilience%20Report %20(Eng_final2).pdf

Rafiq T, O’Leary DD, Dempster KS, Cairney J, Wade TJ. Adverse Childhood Experiences (ACEs) Predict Increased Arterial Stiffness from Childhood to Early Adulthood: Pilot Analysis of the Niagara Longitudinal Heart Study. J Child Adolesc Trauma. 2020 May 30;13(4):505–14.

Schneider M, Kraemmer MM, Weber B, Schwerdtfeger AR. Life events are associated with elevated heart rate and reduced heart complexity to acute psychological stress. Biol Psychol. 2021 Jul 1;163:108116.

Wesarg C, Van den Akker AL, Oei NYL, Wiers RW, Staaks J, Thayer JF, et al. Childhood adversity and vagal regulation: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022 Dec 1;143:104920.

Impact of research: 
The findings of this study can help develop interventions and policies aimed at reducing the impact of ACEs and identifying periods in development where interventions can be directed to change mitigate or reduce the impact of reduced threat perception caused by childhood adversities.
Date proposal received: 
Friday, 6 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Hypertension, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Tachycardia, Statistical methods, Birth outcomes, Blood pressure, Environment - enviromental exposure, pollution, Fathers, Growth, Injury (including accidents), Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, Parenting, Psychology - personality, Physical - activity, fitness, function, BMI, Sex differences, Social science, Statistical methods, Breast feeding, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Development

B4433 - Association of ultra-processed food consumption with body composition and blood pressure in Brazilian and British adolescents - 23/10/2023

B number: 
B4433
Principal applicant name: 
Carolina Abreu de Carvalho | Federal University of Maranhão (Brazil)
Co-applicants: 
Jennifer Carter (PhD)
Title of project: 
Association of ultra-processed food consumption with body composition and blood pressure in Brazilian and British adolescents
Proposal summary: 

The consumption of ultra-processed foods (UPF) has been associated with various adverse health outcomes. However, the investigation of the effect of UPF consumption on obesity, body composition indicators, and blood pressure in adolescents, especially using longitudinal and high-quality studies, is still scarce in the literature. In this context, the present study aims to evaluate the effect of UPF consumption on body composition, obesity, and blood pressure in Brazilian and British adolescents. The comparison of data from adolescents in two countries with distinct socioeconomic and cultural backgrounds, such as Brazil and England, holds unique relevance for advancing knowledge in assessing the detrimental effect of UPF consumption on health, regardless of education or income and other differences between the countries. We hypothesise that there is an association between UPF consumption and body composition, obesity, and blood pressure of adolescents in both countries. The plausibility of this hypothesis is supported by existing evidence in the literature characterizing UPFs as rich in fats, sodium, sugar, and additives, being more high in calories and unhealthy. Therefore, it is likely that the higher consumption of these foods in the long term represents a risk factor for the development of the outcomes analyzed in the present proposal, even in young individuals.

Impact of research: 
The present proposal will investigate the effect of UPF consumption on important cardiovascular risk factors such as blood pressure, changes in body composition and normal weight obesity in Brazilian and British adolescents. We hope that the comparison of data from adolescents from two very different countries will contribute to the advancement of knowledge in verifying the harmful effect of UPF consumption on the outcomes analysed in this proposal. If we observe similar patterns of association between UPF consumption and the outcomes analysed in both countries, despite very different social patterns of intake, this helps to indicate potential causality. Investigating the effect of UPF consumption on cardiovascular risk indicators in adolescents, especially using high-quality longitudinal studies, is still scarce in the literature. Several countries have structured their actions to promote healthy eating based on the logic of the food processing level, therefore, studies that aim to analyse the effects of UPF consumption on health outcomes have the potential to strengthen and improve the evidence base that supports these public food and nutrition actions and policies. Finally, it is worth highlighting that the nutritional transition in England is at a more advanced stage than in Brazil, therefore, comparisons between the two countries can provide relevant contributions so that Brazil can try to anticipate changes that occur as the nutritional transition progresses in the country.
Date proposal received: 
Friday, 6 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Epidemiology, Hypertension, Obesity, Statistical methods, Blood pressure, BMI, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Nutrition - breast feeding, diet

B4430 - CHARGE Metabolomics and Blood Pressure Replication - 23/10/2023

B number: 
B4430
Principal applicant name: 
Neil Goulding | Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol (United Kingdom)
Co-applicants: 
Professor Deborah Lawlor, Professor Bing Yu, Dr Taryn Alkis
Title of project: 
CHARGE Metabolomics and Blood Pressure Replication
Proposal summary: 

High blood pressure (BP) is a major risk factor for cardiovascular as well as non-cardiovascular diseases. Underlying molecular pathways related to BP regulation are not fully understood. The aim of the project is to identify ethnic-specific metabolites associated with cross-sectional measures of blood pressure levels and hypertension status. The project leaders have already found associations between specific metabolites and blood pressure levels or hypertension status in their discovery cohorts. Replication analyses will be conducted in several cohorts that are members of the CHARGE Metabolomics consortium, including ALSPAC.

Impact of research: 
A contribution to the identification of validated metabolomic biomarkers of blood pressure levels and hypertension
Date proposal received: 
Thursday, 19 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Epidemiology, Hypertension, NMR, Blood pressure

B4434 - Body image and risky sun exposure in young people living in a developed country - 23/10/2023

B number: 
B4434
Principal applicant name: 
Carolina Bonilla | Faculty of Medicine, Universidade de São Paulo (Brasil)
Co-applicants: 
Gabriel Hermann
Title of project: 
Body image and risky sun exposure in young people living in a developed country
Proposal summary: 

This project is concerned with the rising incidence of skin cancer[1] and its primary causes, such as exposure to ultraviolet radiation (UVR), highlighting the role of body image on behaviours related to UVR exposure, including sunbathing and indoor tanning.
Body image incorporates body size estimation, evaluation of attractiveness, and emotional responses related to body shape and size[2]. A key aspect is the discrepancy between perceived societal body ideals and one's own appearance, which leads to body dissatisfaction[3]. The incidence of body dissatisfaction is on the rise among young populations in both developed and developing countries[3-4]. In addition, body image has been implicated in various unhealthy behaviours, like harmful weight control practices, disordered eating, smoking, excessive alcohol intake, and sunbed use, which are often interrelated[3].
The current proposal will examine the association between body dissatisfaction and tanning habits in ALSPAC young adults, aiming to identify targets for prevention of behaviours that increase risk for skin cancer in this population.

References

[1] Urban K, Mehrmal S, Uppal P, Giesey RL, Delost GR. The global burden of skin cancer: A longitudinal analysis from the Global Burden of Disease Study, 1990–2017. JAAD International. 2021;2: 98–108. doi:10.1016/J.JDIN.2020.10.013

[2] Grogan S. Body image and health: contemporary perspectives. J Health Psychol. 2006;11: 523–530. doi:10.1177/1359105306065013

[3] Strand M, Fredlund P, Boldemann C, Lager A. Body image perception, smoking, alcohol use, indoor tanning, and disordered eating in young and middle-aged adults: findings from a large population-based Swedish study. BMC Public Health. 2021;21: 128. doi:10.1186/s12889-021-10158-4

[4] Bornioli A, Lewis-Smith H, Smith A, Slater A, Bray I. Adolescent body dissatisfaction and disordered eating: Predictors of later risky health behaviours. Social Science & Medicine. 2019;238: 112458. doi:10.1016/j.socscimed.2019.112458

Impact of research: 
By assessing the influence of body image on UVR exposure, be it natural or artificial, we expect to identify targets for prevention of skin cancer in young adults, who, due to their fair skin phenotypes, are at a disproportionate risk of malignancy.
Date proposal received: 
Monday, 9 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Epidemiology, Mental health, Statistical methods, Environment - enviromental exposure, pollution, body image; sun exposure; indoor tanning; ultraviolet radiation

B4440 - DNA methylation profiles in children in relation to pre- and postnatal exposure to environmental noise LongITools - 25/10/2023

B number: 
B4440
Principal applicant name: 
Ana Goncalves Soares | University of Bristol (United Kingdom)
Co-applicants: 
Kimberley Burrows
Title of project: 
DNA methylation profiles in children in relation to pre- and postnatal exposure to environmental noise (LongITools)
Proposal summary: 

This project will investigate the association between noise exposure during pregnancy and DNA methylation in children

Impact of research: 
Date proposal received: 
Thursday, 19 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Molecular genetics and genomics, Environmental epidemiology, DNA sequencing, Epigenetics

B4439 - Scoping out the linked AWP data - 26/10/2023

B number: 
B4439
Principal applicant name: 
Jon Heron | UOB
Co-applicants: 
Dr Jasmine Raw, Dr Emily Midouhas, Dr Bonamy Oliver, Dr Jane Gilmour
Title of project: 
Scoping out the linked AWP data
Proposal summary: 

We have a current ESRC-funded/ALSPAC-approved project (B3882)

This project will use linked data (with Jasmine and Jon accessing the data through the secure portal).

We are interested in families who have experienced services in relation to their study-child's behavioural problems. Up until recently the plan was to understand service-use through a combination of MHSDS, HES and GP records and we are working on an IRAS form for this, with support from Mark and Eleanor.

Very recently we learned that ALSPAC had obtained some new mental health data - the AWP dataset. We felt that this new data might be of use to us and help fill in some of the gaps left from using MHSDS etc.

Given our research group's clinical experience of MH services we felt it might be beneficial - both to us and to ALSPAC - if we put some effort into understanding these data and produced a data-note or some other kind of documentation for the use of ALSPAC and other interested data-users.

Mark felt it was a reasonable request for us to obtain these data in their entirety, but unlinked to other sources, through the linkage portal. We would then produce a data-note, and hopefully also some derived variable which could be checked before being incorporated into our main linkage data.

Any payments and data-agreements are ongoing and are all linked to the main project. Mark felt it sensible for us to submit a secondary project for this specific scoping aim.

Impact of research: 
Date proposal received: 
Wednesday, 18 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Linkage

B4431 - Diastolic blood pressure across the life course risk factors and consequences - 19/10/2023

B number: 
B4431
Principal applicant name: 
Laura Howe | MRC IEU
Co-applicants: 
Prof Abigail Fraser, Vandana Venkat
Title of project: 
Diastolic blood pressure across the life course, risk factors and consequences
Proposal summary: 

High blood pressure is a risk factor for heart disease. Most research is carried out using systolic diastolic pressure - the pressure in the heart when the heart muscle contracts. Less is known about diastolic blood pressure - the pressure in the heart when the heart muscle relaxes. This project seeks to better understand diastolic blood pressure - what influences is, and what are its consequences for heart health.

Impact of research: 
Improved understanding of diastolic blood pressure
Date proposal received: 
Thursday, 5 October, 2023
Date proposal approved: 
Thursday, 19 October, 2023
Keywords: 
Epidemiology, Blood pressure

B4425 - Menopause and depression assessing causation and identifying mechanisms - 10/10/2023

B number: 
B4425
Principal applicant name: 
Carol Joinson | Population Health Sciences, Bristol Medical School (UK)
Co-applicants: 
Ms Rochelle Knight, Prof Abigail Fraser, Dr Ana Goncalves Soares
Title of project: 
Menopause and depression: assessing causation and identifying mechanisms
Proposal summary: 

Despite the increasing media coverage concerning the impacts of the menopause on women’s mental health, this remains an under-researched area. Menopause affects quality of life, work, and relationships and is also a period of increased risk of depression. Depressive symptoms during menopause are often attributed to hormonal changes, but life stressors that coincide with the menopausal transition could also have a depressogenic effect. Earlier research, based mainly on cross-sectional data, has found that a later age at menopause and a longer reproductive period are associated with a lower risk of depression. This may reflect a greater lifetime exposure to oestrogen, which is thought to have an antidepressant effect in women. Limitations of previous studies include inadequate adjustment for confounders; lack of control for premenopausal depression, and failure to account for other factors affecting lifetime oestrogen exposure (e.g. oral contraceptives, breastfeeding, number of pregnancies) or hormone replacement therapy. Very few studies have sought to uncover the biopsychosocial mechanisms that might explain increased levels of depression during the menopausal transition. This project aims to advance understanding of women’s mental health during menopause by applying cutting edge causal inference methods.

Impact of research: 
This aim of this project is to advance understanding of women’s mental health during menopause by applying cutting edge causal inference methods, and potentially provide new insights into translational targets for interventions. This is a PhD project so research will aim to be published throughout the course of the PhD. Scripts and code will be published on Github to allow for public use. All scientific manuscripts generated from the research will be published on open-access platforms such as Wellcome Open Research or medRxiv. Presentations will be given throughout the PhD to disseminate findings to academic colleagues, at conferences and to the public.
Date proposal received: 
Friday, 29 September, 2023
Date proposal approved: 
Tuesday, 10 October, 2023
Keywords: 
Epidemiology, Mental health, Statistical methods, Mothers - maternal age, menopause, obstetrics

B4426 - Investigating factors associated with within-individual variability in BMI from childhood through to early adulthood - 09/10/2023

B number: 
B4426
Principal applicant name: 
Richard Parker | University of Bristol
Co-applicants: 
Prof. Kate Tilling, Dr Amanda Hughes, Ka Kei Sum
Title of project: 
Investigating factors associated with within-individual variability in BMI from childhood through to early adulthood
Proposal summary: 

Much research has indicated that obesity is associated with poorer health outcomes. Whilst these studies have tended to investigate average body weight (relative to height), more recently there has been interest in variation in body weight. This work has indicated that people whose body weight goes up and down a lot are more likely to experience future weight gain. This project will investigate variability in weight, using body mass index (BMI, a measure of weight which accounts for height), across the key developmental phase of childhood through to early adulthood. It aims to form a better understanding of the factors associated with variability in BMI across this time.

Impact of research: 
Better understanding of the factors associated with within-individual variability in BMI over childhood and early adulthood could provide insight into this phenotype across this key developmental phase, beyond a characterisation of its mean level.
Date proposal received: 
Monday, 2 October, 2023
Date proposal approved: 
Monday, 9 October, 2023
Keywords: 
Epidemiology, Eating disorders - anorexia, bulimia, Obesity, Statistical methods, Statistical methods

B4422 - A multi-cohort analysis of interacting prenatal and genomic risks in the development of childhood ADHD - 09/10/2023

B number: 
B4422
Principal applicant name: 
Ashley Wazana | McGill University
Co-applicants: 
Laurie Haig, Researcher, Eszter Szekely, Co-PI, Francois Freddy-Ateba, Co-Invetigator
Title of project: 
A multi-cohort analysis of interacting prenatal and genomic risks in the development of childhood ADHD
Proposal summary: 

Attention deficit hyperactivity disorder (ADHD) is the most common mental disorder in children worldwide, and can have lifelong health impacts, making it a major public health issue. Rates of ADHD have been increasing in Canada in recent years, particularly in Quebec, and increasing attention has been given to ADHD diagnosis around the world. Previous research suggests there is a significant gender gap in ADHD in children, with boys much more likely to be diagnosed than girls. However, reasons for this difference remain largely unknown. Genetic factors are known to play a key role in the development of ADHD. Yet, genes do not act in isolation. The early environment can also strongly influence brain development and may modify the risk of ADHD. Specifically, maternal stress may alter the prenatal environment to increase the risk of developing ADHD, which may be more likely to impact males due to genetic sex differences. The proposed research aims to analyze the relationship between prenatal maternal stress and offspring sex and genes in relation to the risk of later ADHD diagnosis. This analysis will be carried out in four large independent prenatal cohorts from Canada, the UK (ALSPAC), the Netherlands, and Singapore. Through the use of international, longitudinal data, the proposed project will be able to unpack the complex mechanisms that can result in the development of ADHD across different cohorts and settings. This will lead to a better understanding of the relevant genetic and environmental determinants of ADHD, to allow for better treatment options and identify potential areas of early intervention.

Impact of research: 
This research will be able to create a more complete theoretical model for the determinants of ADHD. The findings of this research will be reported in one manuscript which will be included as a part of the thesis submission and submitted for publication. Such a model will have important implications given the lifelong impacts of this disorder globally. A better understanding of the complex interplay between polygenic, environmental, and sex-related factors underlying ADHD can inform the development of more effective interventions, both early and preventative.
Date proposal received: 
Thursday, 5 October, 2023
Date proposal approved: 
Monday, 9 October, 2023
Keywords: 
Epidemiology, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Genetic epidemiology, Genetics, Sex differences

B4392 - Genetic risk scores for increased levels of endocrine disruptors and pubertal timing - 06/10/2023

B number: 
B4392
Principal applicant name: 
Despoina Manousaki | Research Center of the CHU Sainte-Justine (Canada)
Co-applicants: 
Melody Zuo, Kaossarath Fagbemi
Title of project: 
Genetic risk scores for increased levels of endocrine disruptors and pubertal timing
Proposal summary: 

Puberty is defined as the transition from infancy to reproductive maturity characterized by the acceleration of growth velocity and the development of secondary sexual characteristics and genitals. Normal puberty onset ranges between 8-13 years old for girls, and 9-14 years old for boys. It is clinically defined as the onset of Tanner stage 2 in thelarche for girls (development of breast buds) and by Tanner stage 2 in external genitalia development for boys (increase in testicular volume to >4mL). Age at menarche in girls and age at peak height velocity in both sexes are landmarks which can be used to evaluate pubertal timing.

Endocrine disrupting chemicals (EDCs) have become increasingly prevalent in the past century as manmade products and chemicals have been made essential in our daily lives. There are nearly 85 000 human-made chemicals in the world, and 1000 or more of those could be endocrine disruptors. There are two main types of EDCs: the persistent organic compounds with decade-long half-lives such as dichloro-diphenyl-trichloroethane (DDT) in pesticides and polychlorinated biphenyls (PCBs), and those that have a shorter half-life but can cause long-term health consequences such as phthalates and bisphenol A. EDCs disrupt the body’s delicate endocrine homeostasis by acting as an agonist or antagonist when binding to hormone receptors, thereby causing unwanted effects, such as earlier timing of puberty in girls and boys. The four EDCs of interest in our study are dibutyl phthalate, bisphenol A (BPA), dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyl (PCB).

Phthalates are a large group of omnipresent compounds used as liquid plasticizers. They are found in food packaging, cosmetic products, shampoo, children’s toys and medical device tubing. It was found that first and second-trimester exposure to Bis(2-ethylhexyl) phthalate (DEHP) was associated with increased peripubertal serum estradiol levels, whereas third-trimester exposure was associated to a delay of pubarche onset. BPA is used to make polycarbonate plastic and epoxy resin. It can be found in food packaging, toys, and canned beverages’ linings. At low concentrations, BPA and other phenol compete with endogenous estrogens for binding, whereas at higher concentrations they have anti-androgenic properties.
DDT was used in many organochlorine pesticides and insecticides before being banned in 1972 in multiple countries. In 2006 however, it was reintroduced in some areas by the World Health Organization in order to fight malaria and control other vector-borne diseases. DDT exposure begins prenatally and lasts throughout a lifetime, as it is found in abundance in consumed food products, and is found to have anti-androgenic properties. PCBs were found in lubricants, electrical equipment and plasticizers up until they were banned in 1979. Studies show that childhood exposures of PCBs are associated with earlier pubertal milestones in boys, such as earlier Tanner stages.
Although a large body of evidence from observational studies exists linking EDCs to pubertal timing variations, these associations can be confounded by factors such as low socio-economic status and obesity and cannot establish causality. In the absence of evidence from randomized controlled trials- which would be unethical to employ, the causal link between EDCs and pubertal timing remains undetermined. We have generated preliminary results using two-sample Mendelian randomization for 19 EDCs, most of which do not support a causal association of genetically determined levels of these EDCs with age at menarche in girls or age at voice change or facial hair in boys. Using genetic variants associated with levels of these EDCs, which are not influenced by environmental confounders, we aim to investigate if genetic predisposition to higher levels of these chemicals could affect pubertal timing in ALSPAC children.
In the proposed project, we hypothesize that genetic risk scores (GRS) composed of one to multiple single nucleotide polymorphisms (SNPs) associated with levels of 19 endocrine disrupting chemicals (dibutyl phthalate, BPA, DDT and 16 types of PCBs) in the largest available genome-wide association studies for EDC levels, could be associated to an altered age at menarche in girls or age at peak height velocity in both girls and boys (adjusting for sex) with and without adjusting for BMI SDS at age 8 and socio-economic status.

Impact of research: 
This proposed study holds significant public health improvement potential, as, in combination of the results of our two-sample Mendelian randomization analyses, it will contribute to the understanding of the effect of EDCs on pubertal timing. EDCs are a fairly new threat to human health as they have only been on the rise in the past two centuries, therefore the health repercussions of many new chemicals have not yet been elucidated or understood. Identifying whether there are associations between specific EDCs and the hallmarks of puberty onset (age at menarche and peak height velocity) could contribute to public awareness about the consequences and inform public health policies. Additionally, taking into consideration the potential modifying effect of BMI and socio-economic status could help determine the relationship between early-life body adiposity and environment-related effects on puberty. These findings could further contribute to public health education about the importance of keeping a healthy lifestyle and a healthy BMI, especially in areas of lower socio-economic status that are more vulnerable to EDCs exposure and increased average BMI. Ultimately, the findings from this study could lead to evidence-based interventions aimed at reducing EDCs exposures during critical developmental periods in childhood, and increased awareness about the associations mediated between EDCs and puberty, which could enable better protection for the future generations and encourage other investigations on these topics.
Date proposal received: 
Friday, 4 August, 2023
Date proposal approved: 
Friday, 6 October, 2023
Keywords: 
Endocrinology, Puberty , GWAS, Endocrine - endocrine disrupters

B4424 - Causal inference in adverse childhood experiences research - 04/10/2023

B number: 
B4424
Principal applicant name: 
Laura Howe | MRC Integrative Epidemiology Unit at the University of Bristol (United Kingdom)
Co-applicants: 
Ka Kei Sum, Annie Herbert, Jon Heron
Title of project: 
Causal inference in adverse childhood experiences research
Proposal summary: 

Adverse Childhood Experiences (ACEs) include abuse and neglect, and measures of family dysfunction such as parental substance misuse, intimate partner violence, psychiatric disorders, and separation. People who experience ACEs are more likely to develop adverse health-related behaviours and poor physical and mental health.

There is increasing awareness of the role that adverse childhood experiences (ACEs) can play in influencing poor health-related behaviours, physical, and mental health. The definition of ACEs varies between studies, but the adversities most commonly studied include child maltreatment (e.g., emotional, physical, and sexual abuse; physical or emotional neglect) and measures of household dysfunction (e.g., violence between parents, parental separation and parental substance misuse, mental illness, or criminal behaviour).
ACEs are rising rapidly on policy agendas, and there is a drive within public health and other spheres of public policy to prevent ACEs, develop and implement interventions to support people who have experienced ACEs, promote ACE-aware services, and even to screen people for the number of ACEs they have encountered. The ACEs framework has led to considerable financial investment from the public sector.
ACEs are more common in people living in poverty. We also know that poverty, adversity, and poor health tend to pass down across the generations within a family. This means that if we simply look at the association between ACEs and health, without fully accounting for the broader family context, this may exaggerate the effect of ACEs on health. Yet this is exactly what is done in the majority of scientific research on ACEs. There are very few studies that try to look at whether ACEs actually cause poor health. If we really want to understand how ACEs are influencing health and use this information to design effective policies and interventions with scarce public resources, we need higher-quality evidence.

In this project, we will improve the quality of evidence on whether ACEs causally affect health by analysing data from ALSPAC, which has followed up children and their families across their lives. We will use information about health before and after an ACE has happened, to see whether the ACE led to a change in health, i.e. whether the ACE ‘derails’ someone from the health trajectory they were already on. We can also use information about other ACEs that happened earlier in life, or even ACEs that happened to the parents when they were children. We will look at whether ACEs influence health-related behaviours (smoking, alcohol use, drug use, and physical activity), physical health (obesity, and the health of the heart and lungs), and mental health.

Impact of research: 
Improved understanding of causality of the relationship between ACEs and health.
Date proposal received: 
Friday, 29 September, 2023
Date proposal approved: 
Wednesday, 4 October, 2023
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Obesity, BMI, Childhood - childcare, childhood adversity, Genetic epidemiology, Social science

B4418 - Data Note ALSPAC linked AWP data - 04/10/2023

B number: 
B4418
Principal applicant name: 
Mark Mumme | University of Bristol
Co-applicants: 
Dr Jon Heron, Dr Jasmine Raw
Title of project: 
Data Note ALSPAC linked AWP data
Proposal summary: 

A data note describing the linked data obtained by ALSPAC about the participants in ALSPAC held by AWP (Avon Wiltshire Partnership MH NHS Trust). This will describe the data available for future research.

Impact of research: 
Increase exposure of ALSPAC as a whole, and to promote research into MH using ALSPAC research assets.
Date proposal received: 
Thursday, 21 September, 2023
Date proposal approved: 
Wednesday, 4 October, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, descriptive, Mental Health

B4423 - Youth Vascular Consortium amendment to B3727 - 03/10/2023

B number: 
B4423
Principal applicant name: 
Monique Breslin | Menzies Institute for Medical Research (Australia)
Co-applicants: 
Vimarsha Kodithuwakku, Dr Rachel Climie, Dr Chloe Park
Title of project: 
Youth Vascular Consortium (amendment to B3727)
Proposal summary: 

Cardiovascular disease (CVD) is the leading
cause of death worldwide, accounting for nearly one-third of all deaths, and poses
a major economic burden to the global healthcare system. Thus, the prevention of
CVD is a public health priority and identifying individuals at increased
cardiovascular risk at an early stage is of paramount importance for minimising
disease progression.

Vascular ageing, the decline in vascular structure and function, is an integrated
marker of overall cardiovascular risk burden on the vasculature over time and
ultimately leads to end organ damage in the heart, brain and kidney. While age
dependent arterial damage typically appears in the fifth or sixth decade of life,
there is wide variability between individuals with some displaying early vascular
ageing. Exposure to environmental and genetic factors as early as during
childhood or even during foetal life promotes the development and accumulation of
subclinical vascular changes that directs an individual towards a trajectory of early
vascular ageing. This has led to the concept that vascular age, as opposed to
chronological age, may be better related to the prognosis of CVD.

However, research concerning vascular ageing in early life and/or adolescents is
sparse despite substantial evidence indicating that the formative years of life play
a significant role in contributing to traditional risk factors exhibited in adulthood.
It is unclear what is normal vascular ageing in this population and no large-scale
study has determined what specific factors contribute to accelerated vascular
ageing in early life.

By creating the Vascular Youth Consortium we will be able to address these
unknowns. The findings of which, will be instrumental to clinicians in preventing
the development of overt CVD later in life.

Impact of research: 
There are several expected outcomes from this consortium including: • The establishment of a collated databank containing study data from collaborators worldwide. • The establishment of reference values for vascular ageing in children, adolescents and young adults. • The identification of risk factors that contribute to early vascular ageing in the younger population. • The development of a predictive index of early vascular ageing in children, adolescents and young adults, based on identified risk factors. • A head-to-head comparison between different techniques used to determine vascular ageing in children, adolescents and young adults. The results of the consortium will be instrumental to clinicians in preventing the development of overt CVD later in life.
Date proposal received: 
Wednesday, 27 September, 2023
Date proposal approved: 
Tuesday, 3 October, 2023
Keywords: 
Physiology, Obesity, Medical imaging, Childhood - childcare, childhood adversity

B4420 - Examining the relationship between autism spectrum disorder and paediatric incontinence using a polygenic risk score and Mendeli - 26/09/2023

B number: 
B4420
Principal applicant name: 
Carol Joinson | PHS (United Kingdom)
Co-applicants: 
Dr Christina Dardani, Dr Kimberley Burrows, Mr Olly Bastiani
Title of project: 
Examining the relationship between autism spectrum disorder and paediatric incontinence using a polygenic risk score and Mendeli
Proposal summary: 

Autism spectrum disorder (ASD) is characterised by deficits in social interaction, communication, and language, as well as stereotyped and repetitive behaviours. There is strong evidence from observational studies for comorbidity between ASD and functional incontinence in children including enuresis (bedwetting), daytime urinary incontinence (DUI), and faecal incontinence (FI).

Impact of research: 
The findings have the potential to advance understanding of the link between autism and childhood incontinence and could inform clinicians about which children are at increased risk of problems attaining continence, and therefore target them for early interventions
Date proposal received: 
Monday, 25 September, 2023
Date proposal approved: 
Tuesday, 26 September, 2023
Keywords: 
Epidemiology, Incontinence, Statistical methods, Genetics

B4411 - Exploring maternal and fetal molecular mechanisms of and risk factors for congenital anomalies - 04/10/2023

B number: 
B4411
Principal applicant name: 
Amy Taylor | University of Bristol (United Kingdom)
Co-applicants: 
Professor Deborah Lawlor, Dr Carolina Borges
Title of project: 
Exploring maternal and fetal molecular mechanisms of and risk factors for congenital anomalies
Proposal summary: 

Congenital anomalies (CAs) occur during the intrauterine life and can be identified during pregnancy, at birth or later in life. CAs can be defined as structural (e.g. limb reduction defects) or functional (metabolic disorders). In European countries, CAs affect approximately 2–3% of births. Although consequences vary depending on the type and severity of the condition, CAs are a major cause of fetal death and infant morbidity. Each year, more than 3 million children under the age of 5 die from CAs globally. In addition, many children with CAs and their families experience lifelong complications.

Whilst multiple factors have been identified as causes of CAs, approximately 50% of congenital disorders cannot be linked to a specific cause . Therefore, there is a pressing need for research to identify modifiable causes of CAs. This project aims to explore genetic and molecular mechanisms of CAs as well as risk factors such as maternal lifestyle factors, health and medication use.

Impact of research: 
There are already several papers in progress from the initial MR-PREG analyses. This work will be important for identifying the mechanisms and causes of CAs.
Date proposal received: 
Monday, 25 September, 2023
Date proposal approved: 
Monday, 25 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Mendelian randomisation

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