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.

Click here to export results in Word format.

B4451 - Genotypes phenotypes and environmental correlates of success in weight loss maintenance for children and adolescents - 05/12/2023

B number: 
B4451
Principal applicant name: 
Zhenmi Liu | West China School of Public Health and West China Fourth Hospital, Sichuan University (P.R.China)
Co-applicants: 
Dr. Chenghan Xiao, Dr. Chuan Yu
Title of project: 
Genotypes, phenotypes, and environmental correlates of success in weight loss maintenance for children and adolescents
Proposal summary: 

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.

Impact of research: 
Based on genotypic, phenotypic, and environmental analyses, our research will be beneficial to interventions aiming at sustaining lost weight, one of the most difficult problems for most individuals with obesity.
Date proposal received: 
Thursday, 16 November, 2023
Date proposal approved: 
Monday, 27 November, 2023
Keywords: 
Epidemiology, Obesity, Gene mapping, GWAS, Metabolomics, Proteomics, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Genetic epidemiology, Growth, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism

B4468 - Fish intakes in childhood and neurodevelopmental outcomes - 27/11/2023

B number: 
B4468
Principal applicant name: 
Dr Caroline Taylor | University of Bristol (United Kingdom)
Co-applicants: 
Louisa Nel, Dr Pauline Emmett
Title of project: 
Fish intakes in childhood and neurodevelopmental outcomes
Proposal summary: 

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.

Impact of research: 
The project intends to examine the relationship between childhood intake of fish and neurodevelopmental outcomes. This relationship has not been modelled previously. This would increase knowledge in this area and influence nutrition guidance on fish consumption in childhood.
Date proposal received: 
Tuesday, 21 November, 2023
Date proposal approved: 
Monday, 27 November, 2023
Keywords: 
Epidemiology, Neurodevelopmental indicators - IQ etc, Statistical methods, Childhood - childcare, childhood adversity

B4467 - SITAR enhancements to support generalisable reproducible and efficient state-of-the-art analysis of individual growth curves - 01/12/2023

B number: 
B4467
Principal applicant name: 
Ahmed Elhakeem | MRC IEU (UK)
Co-applicants: 
Title of project: 
SITAR enhancements to support generalisable, reproducible, and efficient state-of-the-art analysis of individual growth curves
Proposal summary: 

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.

Impact of research: 
Date proposal received: 
Tuesday, 21 November, 2023
Date proposal approved: 
Monday, 27 November, 2023
Keywords: 
Epidemiology, Obesity, Statistical methods, Growth, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B4466 - Developmental trajectories in people born after assisted reproductive technology - 01/12/2023

B number: 
B4466
Principal applicant name: 
Ahmed Elhakeem | MRC IEU (UK)
Co-applicants: 
Title of project: 
Developmental trajectories in people born after assisted reproductive technology
Proposal summary: 

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.

Impact of research: 
The project will provide the highest possible quality evidence on the long-term physical and psychological developmental trajectories and key trajectory features in people born after ART. The findings can establish if offspring born by ART should be followed more closely by medical personnel with respect to their long-term physical and psychological development. The project will provide evidence-based guidelines and recommendations for healthcare providers, reproductive specialists, and legislators to ensure their optimal well-being and long-term health.
Date proposal received: 
Tuesday, 21 November, 2023
Date proposal approved: 
Monday, 27 November, 2023
Keywords: 
Epidemiology, Fertility/infertility, Statistical methods, BMI, Cohort studies - attrition, bias, participant engagement, ethics, Development, Growth, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Offspring, Physical - activity, fitness, function

B4463 - Looking through the epigenome to better understand ADHD and co-occurring traits - 23/11/2023

B number: 
B4463
Principal applicant name: 
Doretta Caramaschi | University of Exeter (United Kingdom)
Co-applicants: 
Chun Kwok
Title of project: 
Looking through the epigenome to better understand ADHD and co-occurring 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 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.

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.
Date proposal received: 
Friday, 17 November, 2023
Date proposal approved: 
Thursday, 23 November, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B4464 - Looking through the epigenome to better understand ADHD and co-occurring neurodevelopmental traits - 23/11/2023

B number: 
B4464
Principal applicant name: 
Doretta Caramaschi | University of Exeter (United Kingdom)
Co-applicants: 
Iris Feliks
Title of project: 
Looking through the epigenome to better understand ADHD and co-occurring neurodevelopmental 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 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.

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.
Date proposal received: 
Friday, 17 November, 2023
Date proposal approved: 
Thursday, 23 November, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B4465 - Looking through the epigenome to better understand ADHD and co-occurring neurodevelopmental conditions - 23/11/2023

B number: 
B4465
Principal applicant name: 
Doretta Caramaschi | University of Exeter (United Kingdom)
Co-applicants: 
Ella Swinbourne
Title of project: 
Looking through the epigenome to better understand ADHD and co-occurring neurodevelopmental conditions
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 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.

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.
Date proposal received: 
Friday, 17 November, 2023
Date proposal approved: 
Thursday, 23 November, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B4461 - Maternal Epigenetic age Interpregnancy Interval and Adverse Pregnancy Outcomes - 15/11/2023

B number: 
B4461
Principal applicant name: 
Amanuel Gebremedhin | Curtin University (Australia)
Co-applicants: 
Professor Gavin Pereira, Dr Yunsung Lee
Title of project: 
Maternal Epigenetic age, Interpregnancy Interval and Adverse Pregnancy Outcomes
Proposal summary: 

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.

Impact of research: 
This proposed research could crucially address age-related misconceptions of risk, aiding 1) improved pregnancy spacing guidelines, 2) deeper insights into age-related pregnancy risks, and 3) the development of novel methods to evaluate maternal age's impact on adverse pregnancy outcomes, thereby informing better healthcare strategies for expectant mothers. Our collaborative research team is well-positioned to undertake this project with complementary expertise in epigenetics and bioinformatics, perinatal epidemiology, and bio (statistics). We have an established history of engaging in successful collaborative projects on perinatal research and epigenetic age clock development using DNA methylation data. Reference [1]. Gebremedhin AT, Regan AK, Ball S, et al. Interpregnancy interval and hypertensive disorders of pregnancy: A population‐based cohort study. Paediatric and perinatal epidemiology. 2021;35(4):404-414. [2]. Gebremedhin AT, Regan AK, Ball S, et al. Effect of interpregnancy interval on gestational diabetes: a retrospective matched cohort study. Annals of epidemiology. 2019;39:33-38. e3. [3]. Gebremedhin AT, Tessema GA, Regan AK, Pereira G. Association between interpregnancy interval and hypertensive disorders of pregnancy: Effect modification by maternal age. Paediatric and perinatal epidemiology. 2021;35(4):415-424. [4]. Wise LA, Mikkelsen EM, Sørensen HT, et al. Prospective study of time to pregnancy and adverse birth outcomes. Fertility and sterility. 2015;103(4):1065-1073. e2. [5]. Willis SK, Hatch EE, Wesselink AK, et al. Post-partum interval and time to pregnancy in a prospective preconception cohort. Paediatr Perinat Epidemiol. May 2021;35(3):271-280. doi:10.1111/ppe.12702
Date proposal received: 
Tuesday, 14 November, 2023
Date proposal approved: 
Wednesday, 15 November, 2023
Keywords: 
Epidemiology, Diabetes, Fertility/infertility, Hypertension, Mental health, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Environment - enviromental exposure, pollution, Epigenetics, Fathers, Genetic epidemiology, Mothers - maternal age, menopause, obstetrics, Nutrition - breast feeding, diet, Siblings, Birth outcomes, Blood pressure, BMI, Breast feeding, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Contraception, Endocrine - endocrine disrupters

B4458 - Motor skills in specific learning difficulties and comorbidities re-use data from B3233 - 13/11/2023

B number: 
B4458
Principal applicant name: 
Silvia Paracchini | University of St Andrews (United Kingdom)
Co-applicants: 
Jiuqing Tang
Title of project: 
Motor skills in specific learning difficulties and comorbidities (re-use data from B3233)
Proposal summary: 

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.

Impact of research: 
Impact for supervisor: Motor skills tend to be overlooked in the context on neurodevelopmental conditions. This project might open new line of investigations and might generate data useful for the extended research community. Impact for the student: Jiuqing will familiarise with the ALSPAC data through this project and she is likely to apply subsequently for a separate and independent project approval. Therefore this project will allow her to gain training while addressing an important research question relevant for her PhD thesis.
Date proposal received: 
Friday, 10 November, 2023
Date proposal approved: 
Monday, 13 November, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Learning difficulty, Speech/language problem, Statistical methods, Cognition - cognitive function, Communication (including non-verbal), Development, Handedness, Intelligence - memory, Psychology - personality, Sex differences, Speech and language

B4453 - Understanding Participant Consent and Moderators in Sharing Supermarket Loyalty Card Data in ALSPAC - 13/11/2023

B number: 
B4453
Principal applicant name: 
Romana Burgess | University of Bristol
Co-applicants: 
Dr Anya Skatova, Dr Neo Poon, Poppy Taylor
Title of project: 
Understanding Participant Consent and Moderators in Sharing Supermarket Loyalty Card Data in ALSPAC.
Proposal summary: 

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.

Impact of research: 
This research will contribute to our understanding of participants' decisions to consent to sharing their supermarket loyalty card data, and whether these decisions are predicted by willingness to consent. This will contribute to the frameworks enabling future linkages of shopping data into longitudinal cohorts, as well as to our understanding of sources of sampling biases in shopping data.
Date proposal received: 
Tuesday, 31 October, 2023
Date proposal approved: 
Monday, 13 November, 2023
Keywords: 
Statistics/methodology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Computer simulations/modelling/algorithms, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Linkage

B4457 - Financial difficulties follow on questions - 10/11/2023

B number: 
B4457
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Professor Nic Timpson
Title of project: 
Financial difficulties, follow on questions
Proposal summary: 

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

Impact of research: 
Date proposal received: 
Friday, 10 November, 2023
Date proposal approved: 
Friday, 10 November, 2023
Keywords: 
Social Science, Social science

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.

Pages