Proposal summaries
B4474 - Exploring the Interplay of Genetic Psychosocial and Metabolic-Immune Nexus in Mental Development Trajectories - 18/12/2023
Unraveling the Link Between Our Bodies and Minds
Ever wondered why our mental well-being is so unique to each of us? Our research project is like a treasure hunt for answers. We believe our mental health is indeed influenced by a complex web of factors, with a spotlight on our immune and metabolic systems.
What We're Doing:
We're investigating the interrelationships among our genes, the surrounding environment, and the internal mechanisms of our bodies. These factors significantly impact how we think, feel, and live. Our objective is to comprehend the roles played by our immune and metabolic systems in this intricate web of connections.
Why It's Important:
Mental health is a big part of life, and we want to help people live their best lives. By studying how our genes, environment, and our body's inner processes influence our mental well-being, we aim to uncover new insights into mental health and develop effective interventions.
How We're Doing It:
We're collecting information from a diverse group of individuals, collecting information, and studying their genes. Additiionally, brain imaging is being conducted to gain a better understanding of how the brain works. We'll keep following these individuals over time to observe any changes that may occur.
What We Hope to Discover:
Our goal is to explore the connetion between our immune and metabolic systems and our mental well-being. By connecting the dots between genes, our environment, and how our bodies function, we aimto uncover new ways to enhance people's happiness and overall quality of life.
In a nutshell, our research is like solving a puzzle. We're dedicated to understanding how our genes, the environment, and our body's inner workings come together to create our unique stories and help us live our best lives.
B4470 - Tinnitus and depression in children young adults and the role of religion/spiritual beliefs and behaviours - 05/12/2023
Tinnitus is defined as a sound in the head or ears that occurs in the absence of any external acoustic source and while there is no single agreed-upon definition of tinnitus, it is estimated to affect between 5.1% to 42.7 % of the population, with a higher prevalence in men than women. Most people habituate to tinnitus, however, in some individuals it has a significant impact on their quality of life and causes debilitating problems such as depression, anxiety, frustration and insomnia. Current research suggests a strong association between tinnitus, psychiatric symptoms and psychological distress. Severe tinnitus can lead to distressing catastrophic thoughts, and although suicide is rare, suicidal thoughts are common amongst severe sufferers.
Tinnitus is also a common experience in children and prevalence rates are reported to be similar to the adult population. Insomnia, listening and attention difficulties are the main psychological factors associated with tinnitus in children. However, little is known about the psychological impact of tinnitus in children, yet emerging studies in this field have identified anxiety and depression as problematic emotional response to tinnitus. Furthermore, there has been limited research on how tinnitus manifests in children, and addressing this knowledge gap is crucial in understanding and predicting the relationship between tinnitus and psychological disorders presenting in adulthood, as children develop into adults with or without tinnitus. Therefore, there is a need for further studies to define the life course of tinnitus from childhood to adulthood in order to gain a better understanding of the role early tinnitus and psychological disorders play in the development of tinnitus severity and distress in to adulthood.
Religious and spiritual beliefs and behaviours (RSBB) may provide mechanisms by which people are able to cope with stress or provide a source of social and emotional support. Recent data supports that RSBB can have a positive influence on adults living with sensory impairment, both hearing and vision loss. For children, longitudinal data indicates that RSBB can support psychological adjustment. These data suggest that children in families with RSBB may be at lower risk of psychological disorders if they experience tinnitus.
B4473 - Association between ideal cardiovascular health and grey matter phenotypes in the young - 01/12/2023
Accumulating evidence implicates poor cardiovascular health in later life as a major risk factor for compromised brain health and eventual dementia. How early the association between cardiovascular and brain health begins to emerge, however, is unclear. In 2022, the American
Heart Association (AHA) created ‘Life’s Essential 8 (LE8)’ – a risk score aimed at quantifying ideal cardiovascular health behaviours within large populations in order to predict future disease. This risk score consists of eight modifiable factors known to influence cardiovascular
disease – namely body weight, physical activity, diet, sleep, smoking, total cholesterol, glucose, and blood pressure – and has been shown to already associate with the subclinical development of early cardiovascular risk in from as early as childhood.
B4476 - DNA methylation proxy of alcohol intake - 01/12/2023
DNA methylation patterns in blood samples are known to be influenced by a variety of exposures including lifestyle factors including smoking, alcohol consumption and diet. Although many of these exposures can be reasonably accurately assessed by self-report questionnaire, there are significant advantages to having objective measures of these exposures using biological samples over self-report which is known to be unreliable, especially for long-term exposures. We therefore propose to construct and validate an accurate DNA methylation-based model of long-term alcohol intake using data from a large number of cohort studies including ALSPAC.
B4469 - Investigating whether religion/spiritual beliefs and behaviours moderate associations between hearing and mental health - 01/12/2023
Hearing loss is in the top ten disabilities in England and second globally for prevalence of impairment. In the UK, around 40% of people aged 50 years old and 71% of people aged 70 years and older have hearing loss. Deterioration of hearing typically starts in the 4th decade of life and risk is increased by noise exposure, genetics and social determinants of health.
Acquired hearing loss can affect communication, mental health, social participation, employment and quality of life. Hearing loss is associated with both anxiety and depression. Hearing loss is also associated with higher risk of loneliness and social isolation, with a potentially greater impact for women compared to men. The impact of hearing loss also extends to communication partners, affecting partners’ social life, quality of life and relationship satisfaction.
Religious and spiritual beliefs and behaviours (RSBB) may provide mechanisms by which people are able to cope with stress, or provide a source of social and emotional support. Recent data supports that RSBB can have a positive influence on living with sensory impairment, both hearing and vision loss. Lee and Park (2022) examine activities of successful ageing and health, and the influence of sensory impairment using data from the US 2015–2017 National Survey on Drug Use and Health. They identified that for those with sensory impairment, participation in religious activity was associated with better reported health. A study of older adults living with age related macular degeneration identified that spirituality and religion were important coping factors promoting emotional well-being. This project will investigate whether self-reported hearing difficulties of study parents are associated with poorer mental health, social isolation and loneliness. If poorer outcomes are identified, we will examine whether RSBB moderates the association, using relevant RSBB-linked questions from ALSPAC questionnaires
B4451 - Genotypes phenotypes and environmental correlates of success in weight loss maintenance for children and adolescents - 05/12/2023
Leveraging the genomic and observational data, this study can contribute to revealing the mystery of weight maintenance after weight loss: In most existing obesity interventions, weight loss is always followed by a weight plateau and then weight regain. Only about 15 - 25% of individuals can achieve and maintain a 10% or more significant weight loss with ongoing intervention. In this context, the mystery of weight loss maintenance should be revealed to compare the interactions of weight loss and maintenance.
Therefore, this study aims to explore the genotypes, phenotypes, and environmental correlates of success in weight loss maintenance for children and adolescents by leveraging the genomic and observational data from ALSPAC. According to ALSPAC anthropometry data and the WHO BMI-for-age standards, overweight individuals whose BMI achieves a normal weight range in follow-up years will be enrolled in the analyses. The degree of weight regain will be estimated by the fluctuation of BMI z-scores in follow-up years. This study can be beneficial to interventions aiming at sustaining lost weight, one of the most challenging problems for most individuals with obesity.
B4466 - Developmental trajectories in people born after assisted reproductive technology - 01/12/2023
This project aims to understand the long-term developmental trajectories of people conceived by assisted reproductive technology (ART). ART has led to over 10 million births and is an established and increasingly used treatment for infertility (disease affecting 1 in 6 couples). Addressing concerns that ART is a prenatal stressor that can have adverse effects on offspring long-term health is a major research priority however, existing evidence is limited by use of selected and small samples with short follow-up and lack of repeat measures.
B4467 - SITAR enhancements to support generalisable reproducible and efficient state-of-the-art analysis of individual growth curves - 01/12/2023
Adolescence is characterised by rapid growth in height and changes in body composition. These growth patterns can be influenced by early life factors and have consequences for adult health. The SITAR (Super Imposition by Translation and Rotation) method of growth curve analysis summarises individual growth patterns using three parameters (size, timing, and intensity) that are estimated as random effects, plus a cubic spline estimate of the average growth curve. SITAR was designed to simplify the analysis of adolescent height growth curves in individuals and it explains over 95% of the age-specific variance in height, making it an effective summary of individual growth patterns. However, SITAR assumes a plateau or constant growth at the end of the growth spurt which means it fails to properly fit outcomes whose growth continues into adulthood (e.g., weight, adiposity, lean mass and bone mass) and as such its use beyond height remains limited. SITAR also depends on arbitrary selection of the number and spacing of knots in the cubic spline which makes it susceptible to overfitting and confirmation bias, and it uses older (slower) software to fit models. SITAR random effects can be related to earlier growth-affecting exposures or later health outcomes making it relevant for translational medicine and life course epidemiology however, these analyses are often performed in two-stages which can lead to bias due to underestimated standard errors. Lastly, to overcome data sharing challenges, international consortia are increasingly turning to privacy-preserving software that can facilitate remote multicohort research, with the DataSHIELD platform, one of the most widely used software, however, DataSHIELD currently lacks implementation of SITAR. The aim of this project is improve the generalisability, reproducibility, and efficiency of SITAR and to empower researchers with essential information and tools for the best-practice analysis of individual growth patterns and their determinants and outcomes. The project will address the current limitations described above by tackling the outstanding methodological issues, creating R software to implement the new insights and developing resources to guide researchers through their analyses. Methodological developments will include generalising SITAR to allow it to accurately fit weight, adiposity, lean mass, and bone mass, approaches to fit SITAR models in more efficient software, implementing P-splines as alternatives to estimate of the average growth curve, approaches to obtain unbiased standard errors when relating growth curve features to exposures or outcomes, and DataSHIELD modules to implement SITAR. Methods will be tested using repeated data from four prospective cohort studies from the UK, USA, and Canada, and simulation studies. An R library, workshop, and interactive guidance will enable statisticians and epidemiologists to apply the method relatively simply.
B4468 - Fish intakes in childhood and neurodevelopmental outcomes - 27/11/2023
Seafood is a major source of essential nutrients such as long chain fatty acids, selenium, iodine and vitamin D. There is debate over whether these essential nutrients offset the potential adverse effects of mercury - a widespread environmental toxin which can accumulate in seafood. Current NHS guidance for pregnancy advises eating no more than 2 portions (approximately 280g) oily fish a week. Previous studies have utilised ALSPAC data to assess the possible benefits and harms of different levels of maternal seafood intake during pregnancy on a child's development, e.g., Hibbeln et al. (2007) modelled the association between maternal fish intake during pregnancy and cognitive development in offspring.
However, there is no current modelling of the relationship between childhood intake of fish and neurodevelopmental outcomes in ALSPAC. This project aims to use existing data from ALSPAC, to examine the possibility of a connection between childhood fish intake and cognitive development. We will look at ALSPAC data collected from food frequency questionnaires on fish intake during childhood, as well as later data on neurodevelopmental indicators (IQ, DDS, SDS). This may subsequently assist with informing nutrition guidance on fish intake in childhood.
B4463 - Looking through the epigenome to better understand ADHD and co-occurring 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 indepth
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.
B4464 - Looking through the epigenome to better understand ADHD and co-occurring neurodevelopmental 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 indepth
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.
B4465 - Looking through the epigenome to better understand ADHD and co-occurring neurodevelopmental conditions - 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 indepth
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.
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.
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.
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
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.