Proposal summaries
B4461 - Maternal Epigenetic age Interpregnancy Interval and Adverse Pregnancy Outcomes - 15/11/2023
The length of time between birth and beginning of subsequent pregnancy, interpregnancy interval (IPI) is associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancy, among others, preterm births, low birth weight and preeclampsia. It has also been identified as a potentially modifiable risk factors for these outcomes for planned pregnancies.
Our recent study has indicated that long IPIs (>60 months) are associated with an increased risk of complications that exceed the effects of short intervals (<6 months) after careful confounder control by matching pregnancies to the same women [1,2]. Moreover, another study, which examined the non-linear relationship between IPI and pregnancy complications by maternal age indicated that the risk of preeclampsia and gestational diabetes was greater for older mothers following long IPI. [3] However, the causal interpretations of the long IPI association remain challenging as the possibility of residual confounding cannot be ruled out.
Current guidelines on pregnancy spacing may be misinformed, overlooking the age-related risks of delayed pregnancy because pregnancy delay naturally increases maternal age. Unfortunately, there is limited research on this topic, with only two relevant studies found, [3.4] neither addressing the independent effects of biological aging, or the partition effect of pregnancy spacing (time to pregnancy, TTP and waiting) on adverse pregnancy outcomes.
B4458 - Motor skills in specific learning difficulties and comorbidities re-use data from B3233 - 13/11/2023
The goal of the present study is to systematically investigate the role of motor skills in common developmental difficulties (e.g., dyslexia, dysgraphia, dyscalculia, and ADHD). We expect motor skills may be associated with cognition and language development and could be a predictor which could be assessed at early age. We will use a range of motor skills to study and understand the motor deficits in the comorbidity of disabilities. The longitudinal dimension of the ALSPAC data will also allow us to study the trajectories of these cognitive skills in the neurodevelopmental disabilities.
B4453 - Understanding Participant Consent and Moderators in Sharing Supermarket Loyalty Card Data in ALSPAC - 13/11/2023
This project will evaluate whether participants who indicated in 2018 that they would likely consent to sharing their supermarket loyalty card data, have now consented to share this data in the present day. The project will consider potential moderators of consent – such as age, gender, and SES characteristics – in order to understand potential sampling biases in the novel loyalty card dataset.
B4457 - Financial difficulties follow on questions - 10/11/2023
We have previously asked participants about the cost of living crisis and how they are managing financially. In the current project we will repeat a general question on financial situation and ask some new questions that are concurrently being used by the Millenium cohort. These questions are going out to G1 only and will enable researchers to further understand the impact of the current cost of living crisis on participant's lives
B4454 - TRPA1 in infantile colic - 20/11/2023
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.
B4448 - Risk prediction model for high blood pressure - 08/11/2023
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.
B4455 - Looking through the epigenome to better understand ADHD and co-occurring psycho-neurobehavioural traits - 23/11/2023
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.
B4446 - Predicting the risk of depression and anxiety in early life and adolescence - 02/11/2023
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.
B4447 - Damaging mutations in LXR uncouple lipogenesis from hepatotoxicity and implicate hepatic cholesterol sensing in human liver hea - 06/11/2023
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.
B4444 - Navigating reproductive events and autoimmune disorders - 31/10/2023
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.
B4449 - Thermometer study - association between baby room temp and later asthma - 31/10/2023
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.
B4438 - How does adiposity distribution influence risk of obesity-driven cancers Exploring causality and mechanisms - 31/10/2023
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.
B4437 - Synthetic Health Data for Research Support - an exemplar from a birth cohort - 31/10/2023
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.
B4436 - Epigenetic markers of gender domains distinct from biological sex - 27/10/2023
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.
B4442 - Genetic variation and alcohol use and smoking - contribution to GSCAN GWAS Sequencing Consortium of Alcohol and Nicotine use - 27/10/2023
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.
B4443 - An examination of the association between school absence and exclusion and violent crime - 09/11/2023
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.
B4435 - Understanding the aetiology of Childhood self-harm in the general population An epidemiological approach - 30/10/2023
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.
B4432 - The Impact of Adverse Childhood Experiences on Autonomic Functioning Across the Lifecourse - 23/10/2023
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.
B4433 - Association of ultra-processed food consumption with body composition and blood pressure in Brazilian and British adolescents - 23/10/2023
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.
B4430 - CHARGE Metabolomics and Blood Pressure Replication - 23/10/2023
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.