Proposal summaries
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.
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.
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.
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.