Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B4477 - The role of attachment in infancy with mental and physical health and relationship outcomes in early adulthood - 04/12/2023

B number: 
B4477
Principal applicant name: 
Alexandria Andrayas | School of Psychological Science (UK)
Co-applicants: 
Professor Marcus Munafo, Anna Howard
Title of project: 
The role of attachment in infancy with mental and physical health, and relationship outcomes, in early adulthood
Proposal summary: 

Attachment theory suggests that when babies are born, their main aim is to connect with and stay close to their caregiver. This behaviour has developed over time to help them survive. Scientists have come up with different attachment styles, like secure, avoidant, anxious, and disorganised. Previous studies have found that how well a child bonds with their caregiver can affect things like blood pressure, stress, habits, self-esteem, wellbeing and how they form and keep stable adult relationships. The upcoming research project will investigate the strength and direction of the relationship between attachment and later health and relationship outcomes.

Impact of research: 
If attachment does influence physical and mental health outcomes, and relationship satisfaction, then interventions to improve attachment may improve these outcomes. Health promotion related to these outcomes may also be specifically targeted to those with insecure attachment, given that they will be more likely to experience adverse mental and physical health and relationship outcomes.
Date proposal received: 
Thursday, 30 November, 2023
Date proposal approved: 
Monday, 4 December, 2023
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B4478 - The role of attachment in infancy with mental and physical health and relationship outcomes in early adulthood 2 - 04/12/2023

B number: 
B4478
Principal applicant name: 
Alexandria Andrayas | School of Psychological Science (UK)
Co-applicants: 
Professor Marcus Munafo, Emily Thomas
Title of project: 
The role of attachment in infancy with mental and physical health, and relationship outcomes, in early adulthood 2
Proposal summary: 

Attachment theory suggests that when babies are born, their main aim is to connect with and stay close to their caregiver. This behaviour has developed over time to help them survive. Scientists have come up with different attachment styles, like secure, avoidant, anxious, and disorganised. Previous studies have found that how well a child bonds with their caregiver can affect things like blood pressure, stress, habits, self-esteem, wellbeing and how they form and keep stable adult relationships. The upcoming research project will investigate the strength and direction of the relationship between attachment and later health and relationship outcomes.

Impact of research: 
If attachment does influence physical and mental health outcomes, and relationship satisfaction, then interventions to improve attachment may improve these outcomes. Health promotion related to these outcomes may also be specifically targeted to those with insecure attachment, given that they will be more likely to experience adverse mental and physical health and relationship outcomes.
Date proposal received: 
Thursday, 30 November, 2023
Date proposal approved: 
Monday, 4 December, 2023
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B4479 - The role of attachment in infancy with mental and physical health and relationship outcomes in early adulthood 3 - 04/12/2023

B number: 
B4479
Principal applicant name: 
Alexandria Andrayas | School of Psychological Science (UK)
Co-applicants: 
Professor Marcus Munafo, Noah Chambers
Title of project: 
The role of attachment in infancy with mental and physical health, and relationship outcomes, in early adulthood 3
Proposal summary: 

Attachment theory suggests that when babies are born, their main aim is to connect with and stay close to their caregiver. This behaviour has developed over time to help them survive. Scientists have come up with different attachment styles, like secure, avoidant, anxious, and disorganised. Previous studies have found that how well a child bonds with their caregiver can affect things like blood pressure, stress, habits, self-esteem, wellbeing and how they form and keep stable adult relationships. The upcoming research project will investigate the strength and direction of the relationship between attachment and later health and relationship outcomes.

Impact of research: 
If attachment does influence physical and mental health outcomes, and relationship satisfaction, then interventions to improve attachment may improve these outcomes. Health promotion related to these outcomes may also be specifically targeted to those with insecure attachment, given that they will be more likely to experience adverse mental and physical health and relationship outcomes.
Date proposal received: 
Thursday, 30 November, 2023
Date proposal approved: 
Monday, 4 December, 2023
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B4480 - The role of attachment in infancy with mental and physical health and relationship outcomes in early adulthood 4 - 04/12/2023

B number: 
B4480
Principal applicant name: 
Alexandria Andrayas | School of Psychological Science (UK)
Co-applicants: 
Professor Marcus Munafo, Ella Snape
Title of project: 
The role of attachment in infancy with mental and physical health, and relationship outcomes, in early adulthood 4
Proposal summary: 

Attachment theory suggests that when babies are born, their main aim is to connect with and stay close to their caregiver. This behaviour has developed over time to help them survive. Scientists have come up with different attachment styles, like secure, avoidant, anxious, and disorganised. Previous studies have found that how well a child bonds with their caregiver can affect things like blood pressure, stress, habits, self-esteem, wellbeing and how they form and keep stable adult relationships. The upcoming research project will investigate the strength and direction of the relationship between attachment and later health and relationship outcomes.

Impact of research: 
If attachment does influence physical and mental health outcomes, and relationship satisfaction, then interventions to improve attachment may improve these outcomes. Health promotion related to these outcomes may also be specifically targeted to those with insecure attachment, given that they will be more likely to experience adverse mental and physical health and relationship outcomes.
Date proposal received: 
Thursday, 30 November, 2023
Date proposal approved: 
Monday, 4 December, 2023
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B4474 - Exploring the Interplay of Genetic Psychosocial and Metabolic-Immune Nexus in Mental Development Trajectories - 18/12/2023

B number: 
B4474
Principal applicant name: 
Jianhua Chen | Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine (China)
Co-applicants: 
Title of project: 
Exploring the Interplay of Genetic, Psychosocial, and Metabolic-Immune Nexus in Mental Development Trajectories
Proposal summary: 

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.

Impact of research: 
Our research will advance the understanding of the complex interplay between genetic, psychosocial, metabolic, and immune factors in mental health, contributing to scientific progress. By uncovering novel pathways and mechanisms, our study has the potential to lead to more effective, personalized interventions and treatments, enhancing mental health outcomes. We hope our findings may foster interdisciplinary collaboration, enhancing research and practice.
Date proposal received: 
Tuesday, 28 November, 2023
Date proposal approved: 
Friday, 1 December, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Allergy, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Diabetes, Eating disorders - anorexia, bulimia, Eczema, Hypertension, Mental health, Obesity, Computer simulations/modelling/algorithms, DNA sequencing, Gene mapping, GWAS, Microarrays, NMR, Proteomics, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Blood pressure, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Hormones - cortisol, IGF, thyroid, Immunity, Mendelian randomisation, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, BMI, Parenting, Psychology - personality, Whole genome sequencing, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Endocrine - endocrine disrupters, Environment - enviromental exposure, pollution, Epigenetics

B4469 - Investigating whether religion/spiritual beliefs and behaviours moderate associations between hearing and mental health - 01/12/2023

B number: 
B4469
Principal applicant name: 
Neil Goulding | Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol (United Kingdom)
Co-applicants: 
Dr Amanda Hall
Title of project: 
Investigating whether religion/spiritual beliefs and behaviours moderate associations between hearing and mental health
Proposal summary: 

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

Impact of research: 
Identification of associations between hearing impairment and depression/anxiety.
Date proposal received: 
Tuesday, 21 November, 2023
Date proposal approved: 
Friday, 1 December, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B4476 - DNA methylation proxy of alcohol intake - 01/12/2023

B number: 
B4476
Principal applicant name: 
Matthew Suderman | IEU, University of Bristol (UK)
Co-applicants: 
Professor Riccardo Marioni, Aleksandra Chybowska
Title of project: 
DNA methylation proxy of alcohol intake
Proposal summary: 

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.

Impact of research: 
The alcohol intake DNA methylation model will allow researchers to objectively assess long-term alcohol consumption behaviors to better understand the causes and effects of alcohol consumption.
Date proposal received: 
Wednesday, 29 November, 2023
Date proposal approved: 
Friday, 1 December, 2023
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Microarrays, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics

B4473 - Association between ideal cardiovascular health and grey matter phenotypes in the young - 01/12/2023

B number: 
B4473
Principal applicant name: 
Scott Chiesa | UCL (UK)
Co-applicants: 
Fatehah Jahan
Title of project: 
Association between ideal cardiovascular health and grey matter phenotypes in the young
Proposal summary: 

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.

Impact of research: 
First evidence in large adolescent cohort (at time of outcome measurement) showing association between cumulative CV risk assessed through recognised metric and early differences in brain health.
Date proposal received: 
Monday, 27 November, 2023
Date proposal approved: 
Friday, 1 December, 2023
Keywords: 
Epidemiology, cardiovascular health, brain health, phenotyping, risk scores, Blood pressure, BMI, Cardiovascular, Neurology, Physical - activity, fitness, function, Sleep

B4470 - Tinnitus and depression in children young adults and the role of religion/spiritual beliefs and behaviours - 05/12/2023

B number: 
B4470
Principal applicant name: 
Amanda Hall | Aston University
Co-applicants: 
Nadia Donald, Professor Jean Golding, Yaz Iles-Caven, Dr Dan Green
Title of project: 
Tinnitus and depression in children & young adults, and the role of religion/spiritual beliefs and behaviours
Proposal summary: 

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.

Impact of research: 
Increase understanding of the generation of severe tinnitus, which has potential to improve clinical interventions Further understanding of how religious & spiritual beliefs and behaviours do or do not interact with health conditions
Date proposal received: 
Wednesday, 22 November, 2023
Date proposal approved: 
Friday, 1 December, 2023
Keywords: 
Epidemiology, Tinnitus & mental health, Statistical methods, ENT - hearing

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

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

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

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