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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B4454 - TRPA1 in infantile colic - 20/11/2023

B number: 
B4454
Principal applicant name: 
Laurent FERRIER | Nestlé Research (Switzerland)
Co-applicants: 
Eleonora Porcu
Title of project: 
TRPA1 in infantile colic
Proposal summary: 

Infantile colic is a common condition that affects babies within the first few months of life. It is characterized by episodes of excessive crying, often occurring in the late afternoon or evening. Babies with colic may cry inconsolably for extended periods, typically following "the rule of three" : at least three hours a day, three days a week, for three weeks or more . The crying episodes can be intense and may be accompanied by signs of discomfort, such as clenched fists, arched back, and a flushed face. It is important to note that colic is not caused by anything the parents have done or by any underlying medical condition.

The exact cause of colic is unknown, but it is believed to be related to the baby's immature digestive system, sensitivity to stimulation, or difficulty in self-soothing. Our aim here is to determine if a particular receptor called TRPA1 could be involved in the genesis of the pain.

Impact of research: 
Infantile colic is a frequent condition characterized with abdominal pain triggering long periods of crying with difficulty to soothe. This is difficult to manage for parents who may feel distraught. It is indeed the first risk factor for the shaken baby syndrome. The etiology of colic remains largely unknown as it impacts both genders, caesarean- or vaginally-born infants, and breastfed as well as formula-fed infants. Our hypothesis is that the receptor TRPA1 represents a good candidate to generate pain symptoms in colicky infants. We therefore would like to test the association between TRPA1 SNPs and colicky phenotype. This would allow to better understand the reason why infants may be more sensitive to painful stimuli. Ultimately, these findings could lead to develop solutions targeting TRPA1 receptor.
Date proposal received: 
Wednesday, 1 November, 2023
Date proposal approved: 
Friday, 10 November, 2023
Keywords: 
Physiology, Gastrointestinal, Statistical methods, Genetics

B4448 - Risk prediction model for high blood pressure - 08/11/2023

B number: 
B4448
Principal applicant name: 
Rahul Chanchlani | McMaster University (Canada)
Co-applicants: 
Manish Sinha, Emily Haseler
Title of project: 
Risk prediction model for high blood pressure
Proposal summary: 

Background:
High blood pressure is becoming more common in children due to factors like obesity, lack of physical activity, and a high-salt diet. High blood pressure in childhood can lead to heart problems and kidney diseases in adulthood.

Purpose:
Regular blood pressure screening for all healthy children is recommended after the age of 3. However, regular screening can be burdensome and lead to unnecessary anxiety, overdiagnosis, and harm. The goal of our study is to develop a tool that can identify children at risk for high blood pressure, making the screening process more targeted and efficient. Our group, including doctors, researchers and patients, aim to develop a tool that can accurately estimate the likelihood of children who are at risk of BP at age of 5 years.

Methods:
Data from various national (n=4) and international (n=1) pediatric studies will be used to develop and validate this tool. It will consider factors such as parental characteristics (ethnicity, maternal age, body mass index, education status, etc), birth-related factors (birth weight, gestational age, etc), and early childhood factors (sex, breast feeding duration, weight, etc )known to be associated with high blood pressure.

Anticipated Outcomes:
The tool will simplify the process of screening for high blood pressure in children. It can be a first step in preventing heart and kidney diseases in the future.

Patient Engagement:
A patient partner, a mother of a child with high blood pressure, is involved in the project and provides valuable feedback.

Relevance to Patients/Community:
High blood pressure in children is now recognized as a potential risk for future heart and kidney issues. The study aims to create awareness about this tool and educate families about their child's risk for high blood pressure. Early intervention can make a significant difference in preventing abnormal blood pressure in children.

Conclusion:
The tool will help identify the risk of high blood pressure in early childhood, allowing for early referrals and potential prevention or treatment of kidney and heart complications.

Impact of research: 
Timely detection and treatment of high BP among children is imperative for future prevention of CVD. This project addresses a major knowledge and health care gap and offers a unique opportunity to examine early life determinants of BP in a large cohort of children enrolled in 4 well-defined, diverse longitudinal studies. In addition, this model will be developed using information that is usually recorded or is easy to obtain in communitybased child healthcare practice. Incorporating a prediction model into clinical practice may support decision making regarding testing and referral and help guide community-based healthcare professionals in better distributing their time and efforts, by identifying children that need screening and monitoring of BP and allowing them to pay more attention toward at-risk children in the form of tailored lifestyle and nutritional advice. This can be seen as a first step towards targeted primordial prevention of CVD.
Date proposal received: 
Tuesday, 7 November, 2023
Date proposal approved: 
Wednesday, 8 November, 2023
Keywords: 
Health Services Research/Health Systems Research, Hypertension, Computer simulations/modelling/algorithms, Statistical methods, Birth outcomes, Blood pressure, BMI, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics

B4455 - Looking through the epigenome to better understand ADHD and co-occurring psycho-neurobehavioural traits - 23/11/2023

B number: 
B4455
Principal applicant name: 
Doretta Caramaschi | University of Exeter (United Kingdom)
Co-applicants: 
Ruby Fryer, Iris Felikis, Ella Swinbourne, Chun Kwok
Title of project: 
Looking through the epigenome to better understand ADHD and co-occurring psycho-neurobehavioural traits
Proposal summary: 

Attention-Deficit Hyperactivity Disorder
(ADHD) has symptoms of inattention, hyperactivity, or both. However, patients
with ADHD often experience symptoms of other disorders such as autism spectrum
disorder (ASD), epilepsy, conduct disorder, or anxiety symptoms. Previously, it was
reported that there are shared heritability and cognitive process across the
conditions, implying that there are common underlying biopsychological factors
that have not been identified. Epigenetic biomarkers, especially blood DNA
methylation (DNAm) became significantly important in understanding
neurodevelopmental disorders such as ADHD. Even though the associations
between DNAm and each condition were investigated, there is a limited amount of
research on DNAm biomarkers across ADHD-related phenotypes (ADHD and cooccurring
symptoms). We hypothesized that the underlying biological factors
would be specific to clusters of conditions and could be used as a diagnosis factor
for children. Therefore, we propose to investigate the relationships between each
of the individual traits linked to ADHD and DNAm to reveal their epigenetic
similarities and differences. The epigenetic similarities and differences will give in-depth
insight to understand ADHD. We will use a series of computational methods
including EWAS and machine learning to investigate the DNAm biomarkers of
complex ADHD-related phenotypes from around 1500 participants from the Avon
Longitudinal Study of Parents and Children.

Impact of research: 
This work will impact both families of children with ADHD and clinicians to have better understanding of ADHD and co-occurring conditions. This research may guide the families to know what other conditions their children with ADHD would experience and how to manage the co-occurring condition. Moreover, this research might suggest different approach to the diagnosis of ADHD instead of diagnosis solely on symptoms of inattention and hyperactivity. As this is a student project, it will also benefit the development of data science skills in psychology students.
Date proposal received: 
Monday, 6 November, 2023
Date proposal approved: 
Tuesday, 7 November, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), ADHD, Statistical methods, Epigenetics

B4446 - Predicting the risk of depression and anxiety in early life and adolescence - 02/11/2023

B number: 
B4446
Principal applicant name: 
Hannah Jones | University of Bristol (UK)
Co-applicants: 
Sophie Fairweather, Professor Golam Khandaker
Title of project: 
Predicting the risk of depression and anxiety in early life and adolescence
Proposal summary: 

One in every eight people in the world have a mental health problem[1] and in 75% of these people their mental health problem develops before they are 18[2]. Depression and anxiety are the most common mental health problems and they often co-occur in the same individual. Early-life mental health problems, including depression and anxiety, can severely impact the lives of affected individuals including future health and wellbeing, education and jobs, and family and peer relationships. Therefore, research is needed to improve our understanding of why some people experience mental health problems while others don’t. While depression and anxiety symptoms are often time limited in some people, they are chronic in many, but currently there is no accurate/reliable way of predicting who might develop chronic/severe course of symptoms/illness. Identifying this subgroup would help in development of targeted prevention strategies.

Potential risk factors for mental illnesses include biological factors (e.g., genetics, epigenetics, low-grade inflammation), social factors (e.g., abuse, bullying, living in poverty) and psychological factors (e.g., internalising attributional style).
Evidence has shown that inflammation in the body is an important biological risk-factor[3, 4]. Inflammation can also be triggered or altered by other experiences (for example, eating certain foods, substance use or having an infection). Because of this, it is possible that modifying factors that cause inflammation (e.g., diet) may help to treat or prevent mental health problems.

An important group, who might have more inflammation, are people with food allergies, eczema and asthma. Allergy is very common; researchers predict that by 2025 half of all people living in Europe will have an allergy[5]. Psychosocial factors linked to allergy such as trauma associated with a severe allergic reaction, fear of experiencing a reaction, following a restricted diet, social exclusion, missing days from school, medication use and over-protective parenting styles might also influence a child’s mental health.

This project will use data collected from participants of the Avon Longitudinal Study of Parents and Children who answered questions about their mental health, and other life experiences, at different ages as they grew up. We will use these data to look at how bio-psycho-social risk factors in early life (e.g., gestation, childhood, adolescence) are linked to mental health in teenagers and young adults. Findings will enable us to identify and help children who are at high risk of developing a mental health problem before they have developed severe, adverse symptoms.

1. (WHO), W.H.O., Fact sheets: Mental Disorders. 2022.
2. England, M., Mental health statistics. 2020.
3. Milaneschi, Y., et al., Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. Mol Psychiatry, 2021. 26(12): p. 7393-7402.
4. Foley, É.M., et al., Peripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis. Molecular Psychiatry, 2023. 28(3): p. 1004-1019.
5. UK, A., Statistics and Figures. Allergy Prevalence: Useful facts and figures.

Impact of research: 
Broadly, this work will contribute to understanding the role of early life experiences, and the role of the immune system, in psychiatric illness. Understanding trajectories of early life experiences and which bio-psycho-social factors contribute to later mental health outcomes is important for predicting risk among other factors that might also be useful. In turn, risk prediction is an opportunity for early, targeted, preventative intervention which may also involve strategies to reduce inflammation (pharmacological and/or otherwise). A specific aim of this project is to develop a prediction tool for use in community settings (e.g., schools) to identify children in need of mental health and social support. While other models have been published (in other, smaller cohorts), few are translated into clinical/community tools and models rarely predict anxiety (more commonly depression). In the future, the real-world utility of the risk prediction tool could be tested and a future work program focusing on consequences of depression and anxiety trajectories, including functional outcomes, could be explored.
Date proposal received: 
Thursday, 26 October, 2023
Date proposal approved: 
Thursday, 2 November, 2023
Keywords: 
Epidemiology, Allergy, Eczema, Infection, Mental health, Respiratory - asthma, Computer simulations/modelling/algorithms, Statistical methods, Prediction

B4447 - Damaging mutations in LXR uncouple lipogenesis from hepatotoxicity and implicate hepatic cholesterol sensing in human liver hea - 06/11/2023

B number: 
B4447
Principal applicant name: 
Kushala Abeysekera | University of Bristol (United Kingdom)
Co-applicants: 
Dr Sam Lockhart
Title of project: 
Damaging mutations in LXR uncouple lipogenesis from hepatotoxicity and implicate hepatic cholesterol sensing in human liver hea
Proposal summary: 

We are interested in how metabolic dysfunction leads to liver disease. While it is well known that having a ‘fatty liver’ is a risk factor for liver inflammation and scarring – so-called cirrhosis, the specific mechanisms that drive this relationship are not well understood. Cholesterol, has a well described role in the development of heart disease and stroke, but it is actually increased in people with fatty liver disease – but if it is truly harmful and how it may cause harm is not clear.

In previous work, we have studied the role of a protein that has a key role in limiting cholesterol accumulation inside liver cells, LXRalpha. We have found that people who carry rare mutations in the DNA that tells the body how to make this protein have evidence of subtle liver damage despite actually seeming to be protected from accruing liver fat. We have also made a mouse model that has no functional LXRalpha and these mice develop severe liver injury with marked scarring whenever they are exposed to a fatty diet with cholesterol.

Together these findings provide evidence that this protein, and liver cholesterol metabolism generally, are important in maintaining liver health in humans. However, we have studied this in a large study called UK biobank, a study of older individuals who tend to be healthier than the general population and have mostly been studied at a single time point. Using Alspac, we want to understand if these findings are valid in a younger population and to characterise the dysfunctional LXRalpha on human liver health over time. We expect that replicating our findings in Alspac will demonstrate the robustness and generalisability of our findings and confirm the role of LXRalpha in maintaining human liver health.

Impact of research: 
This will guide therapeutic drug development to prevent liver injury. There is currently interest in developing LXR agonists to treat steatohepatitis, but this might be problematic due to pleiotropic effects of LXRalpha that the Cambridge group have evidenced in adults.
Date proposal received: 
Thursday, 26 October, 2023
Date proposal approved: 
Thursday, 2 November, 2023
Keywords: 
Genetics, Metabolic health, lipid metabolism, liver disease , Metabolomics, Metabolic - metabolism

B4444 - Navigating reproductive events and autoimmune disorders - 31/10/2023

B number: 
B4444
Principal applicant name: 
Kayleigh Easey | University of Bristol, School of Psychological Science (United Kingdom)
Co-applicants: 
Dr Robyn wootton
Title of project: 
Navigating reproductive events and autoimmune disorders
Proposal summary: 

During pregnancy, many important biological and physiological changes occur to protect both mother and the growing baby, particularly related to hormones and the immune system. We also know that compared to men, women are more likely to have autoimmune disorders, where the body's defence system attacks itself. However, pregnant women are often excluded from studies because of safety implications. We now need to figure out how reproductive hormones might impact autoimmune disorders in both pregnant and non-pregnant people, as well as what other health behaviours may influence this.

Impact of research: 
The impact of this research will to expand knowledge within a hard to research area of particular health behaviours and their relationship to reproductive events. Journal articles and conference presentations will be expected from this research.
Date proposal received: 
Tuesday, 24 October, 2023
Date proposal approved: 
Tuesday, 31 October, 2023
Keywords: 
Epidemiology, Mental health, Statistical methods, Birth outcomes

B4449 - Thermometer study - association between baby room temp and later asthma - 31/10/2023

B number: 
B4449
Principal applicant name: 
Jean Golding | UoB
Co-applicants: 
Professor Kate Northstone
Title of project: 
Thermometer study - association between baby room temp and later asthma
Proposal summary: 

During the last 6 months (may - Dec 1992) of recruitment to the study, mothers were randomised to receive a simple thermometer or not. Those who received one, were asked to place in the wall of the room where her baby slept. She was asked to record the temperature of the room twice a week for a year. This project will clean the data obtained and will derive a number of sumamry variables regarding temperature with a view to looking at later respiratory outcomes in the children up to the age of 18 years.

Impact of research: 
The presence of a thermometer in a child's bedroom may have an impact on child health. if extremes of temperature are shown to have an impact on later child health then advice can be provdied to mothers to adjust baby room;s temperature in order to optimise health.
Date proposal received: 
Friday, 27 October, 2023
Date proposal approved: 
Tuesday, 31 October, 2023
Keywords: 
Epidemiology, Respiratory - asthma, Environment - enviromental exposure, pollution

B4438 - How does adiposity distribution influence risk of obesity-driven cancers Exploring causality and mechanisms - 31/10/2023

B number: 
B4438
Principal applicant name: 
Emma Vincent | University of Bristol (United Kingdom)
Co-applicants: 
Emma Hazelwood
Title of project: 
How does adiposity distribution influence risk of obesity-driven cancers? – Exploring causality and mechanisms.
Proposal summary: 

Obesity, which is increasing worldwide, is known to increase a person’s risk of many health conditions. The amount of fat tissue that an individual has is often proxied using body mass index (BMI). BMI is cheap to measure and can be an effective measure of overall fat tissue when used at a population level. However, BMI cannot capture the full complexity of the distribution of fat tissue across the body. Recent research has highlighted that fat tissue at different locations throughout the body can have vastly different consequences for heart and blood outcomes, with more central fat tissue having negative consequences and more thigh and buttock fat tissue being beneficial. Whether similar effects of fat tissue distribution are also seen in cancer outcomes, particularly for cancers where there is a known link with obesity, is not yet unknown.
We aim to use ALSPAC data to gain a deeper understanding of the link between fat tissue distribution throughout the body and cancer risk. We will evaluate whether fat tissue distribution affects cancer risk and levels of certain molecular traits measured in blood samples at different ages using the latest statistical methods.
The proposed research will increase our understanding of how fat tissue distribution affects cancer risk. We will also unpick the potential biological mechanisms explaining these relationships and determine at what age the relationships may begin.

Impact of research: 
The direct outcome of our study is a greater understanding of which measures of adiposity are relevant for which obesity-related cancers, the molecular mechanisms that may be underpinning these relationships, and the age at which these relationships can be observed. Beyond contributing to our understanding of the vitally important relationship between adiposity and cancer risk, this study will provide the basis for more tailored obesity treatment recommendations for individuals at increased risk of particular cancers.
Date proposal received: 
Tuesday, 17 October, 2023
Date proposal approved: 
Tuesday, 31 October, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Cancer, Obesity, GWAS, Medical imaging, Proteomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Genetic epidemiology, Mendelian randomisation, Metabolic - metabolism, Statistical methods

B4437 - Synthetic Health Data for Research Support - an exemplar from a birth cohort - 31/10/2023

B number: 
B4437
Principal applicant name: 
Mark Mumme | University of Bristol
Co-applicants: 
Dr Eleanor Walsh, Dr Daniel Major-Smith, Prof Kate Northstone
Title of project: 
Synthetic Health Data for Research Support - an exemplar from a birth cohort
Proposal summary: 

Electronic health records (EHRs) are a valuable resource in research, with the potential to increase sample size, reduce biases and improve representativeness, by being collected on national scale at the point of care by health care providers. Due to the personal and sensitive nature of EHRs, the confidentiality of these data is protected by strict regulatory frameworks. Accessing EHRs can take months or even years; this remains a major barrier for researchers gaining timely access to real world data. We propose to use the ALSPAC setting as an exemplar project synthesising EHRs in a cohort context. We will develop a roadmap of the key requirements for synthesising EHRs within a cohort setting.

Impact of research: 
This project will provide a roadmap of key requirements for syntheising EHRs applied in a cohort setting, as well as an evaluation of current approaches.
Date proposal received: 
Monday, 16 October, 2023
Date proposal approved: 
Monday, 30 October, 2023
Keywords: 
Statistics/methodology, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

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

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