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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B4531 - Fetal and Infant Growth and Childhood Behavior and Cognitive Outcomes Individual Participant Data Meta-analysis 95000 children - 26/02/2024

B number: 
B4531
Principal applicant name: 
Romy Goncalves | Erasmus MC/Generation R (Netherlands)
Co-applicants: 
MD. PhD. V. W.V. Jaddoe
Title of project: 
Fetal and Infant Growth and Childhood Behavior and Cognitive Outcomes: Individual Participant Data Meta-analysis 95,000 children
Proposal summary: 

In this project we will examine the associations of fetal and infant growth with behavior and cognitive outcomes in children between 4 and 15 years old. Specifically, we will evaluate the effect of birth weight, gestational age at birth, gestational age adjusted birth weight and internalizing and externalizing problems, attention-deficit hyperactivity disorder symptoms, autism spectrum disorder traits and non-verbal IQ. Furthermore, we will examine the associations of growth patterns between birth weight and infancy body mass index and the same behavior and cognitive outcomes. For this study, we will use harmonized data from birth cohort studies across Europe and analyze this data combined.

Impact of research: 
Date proposal received: 
Monday, 12 February, 2024
Date proposal approved: 
Monday, 26 February, 2024
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Growth

B4536 - Growing up in turbulent times Wellbeing of adolescents in a longitudinal and cross-cultural perspective - 20/02/2024

B number: 
B4536
Principal applicant name: 
Rebecca Lacey | St George's, University of London (UK)
Co-applicants: 
Prof Anne McMunn, Dr Gabriela Ksinanova
Title of project: 
Growing up in turbulent times. Wellbeing of adolescents in a longitudinal and cross-cultural perspective
Proposal summary: 

Large scale societal crises, e.g. recessions, pandemics, can have long-lasting effects on health and wellbeing. This is particularly the case when experienced at important times in life, such as in adolescence. Adolescence (age 10-25) is a time when young people experience many changes in terms of biological, social and cognitive development. It is also a time when many important transitions are made. For instance, leaving the family home, leaving school and entering further or higher education and work, and forming partnerships and families. Therefore, experiencing societal crises during this life stage may be particularly challenging and disruptive.

This project will look at the impact that societal crises have on the lives of adolescents across Europe. We will use comparable longitudinal datasets to examine the impacts that the Post-Communist Transformation had on families in Eastern Europe, the impact of the Covid pandemic on adolescent transitions, and the effect of the Great Recession in 2008.

This work forms part of a large, cross-European project for which we are currently seeking funding. The project uses large longitudinal datasets from multiple countries. ALSPAC provides an important comparator cohort to the Czech ELSPAC study. The Czech cohort were born during the time of great upheaval during the Post-Communist Transformation of the early 1990s. At this time there was growing socioeconomic inequality. In contrast, the ALSPAC cohort were born into a society with wide, persistent socioeconomic inequality. By directly comparing these two cohorts we will be able to look at the consequences of the Post-Communist Transformation and more broadly, family socioeconomic inequalities, for family mental health, particularly the mental health and wellbeing of adolescents.

Impact of research: 
This study will document the long-term impacts of the Post-Communist Transformation and other societal crises for adolescent mental health and wellbeing. By documenting the short and long-term consequences of societal crises we will be better able to respond to these crises in the future. We are working with various stakeholders across Europe. In the UK, our partner organisation is the newly formed Centre for Young Lives. We will be working with this and other European organisations to produce policy briefs, present webinars, and produce academic outputs e.g. peer-reviewed publications, conference presentations etc.
Date proposal received: 
Wednesday, 7 February, 2024
Date proposal approved: 
Tuesday, 20 February, 2024
Keywords: 
Epidemiology, Mental health, Childhood - childcare, childhood adversity, Sex differences, Social science

B4538 - Genome-Wide Association Study of Lipid Traits and the influence of Body-Mass Index and Age - 20/02/2024

B number: 
B4538
Principal applicant name: 
Marisa Canadas Garre | University of Bristol (United Kingdom)
Co-applicants: 
Professor Nicholas Timpson, Dr Laura Corbin
Title of project: 
Genome-Wide Association Study of Lipid Traits and the influence of Body-Mass Index and Age
Proposal summary: 

The Global Lipids Genetics Consortium (GLGC) is a world-wide collaboration of investigators dedicated to understanding how the different variants in genes can influence the blood levels of lipid traits, such as cholesterol, triglycerides, etc. In our study, we will analyse the association of gene variants with blood lipid levels, considering the effect of age and body-mass index in ALSPAC participants. The results will be combined with results from other groups of participants around the world to be able to identify new gene variants that help understand the biology of blood lipid traits.

Impact of research: 
Greater understanding of the aetiology of blood lipids. This study will help identify novel genetic variants involved in lipid traits and how genetic variants affect these traits considering potential interactions with either BMI or age.
Date proposal received: 
Friday, 9 February, 2024
Date proposal approved: 
Tuesday, 20 February, 2024
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Hypertension, Obesity, Hypercholesterolemia, Computer simulations/modelling/algorithms, Gene mapping, GWAS, Metabolomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Statistical methods, Blood pressure, BMI, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Metabolic - metabolism

B4542 - Identifying markers for brain signatures of adolescent depression and depression risk - part 2 - 20/02/2024

B number: 
B4542
Principal applicant name: 
Alex Kwong | MRC IEU / University of Edinburgh
Co-applicants: 
Ms Christina Steyn
Title of project: 
Identifying markers for brain signatures of adolescent depression and depression risk - part 2
Proposal summary: 

We are requesting permission for a PhD rotation student to analyse existing data that is held at the University of Edinburgh under the proposal B3860. We do not require any more data, only to allow the student access to this data so they can replicate some analysis that has been done in Generation Scotland.

B3860 is examining: investigating the brain signatures of
adolescent depression and depression risk. In order to fully examine this project,
we are running some initial analysis to define the most robust markers of
depression across adolescence. From preliminary analysis and other research, we
have found that trajectories of depressive symptoms may be robust markers for
some brain signatures. Additionally, these trajectories could mediate the
relationship between early risk factors and later brain signatures.

Impact of research: 
Date proposal received: 
Friday, 16 February, 2024
Date proposal approved: 
Tuesday, 20 February, 2024
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Statistical methods, Genetic epidemiology

B4535 - How Childhood Dietary Patterns Shape Adolescence-to-Early Adulthood Metabolic Health and Immune Response - 26/02/2024

B number: 
B4535
Principal applicant name: 
Ruifang Li | Leiden University Medical Center (Netherlands)
Co-applicants: 
Keyong Deng
Title of project: 
How Childhood Dietary Patterns Shape Adolescence-to-Early Adulthood Metabolic Health and Immune Response
Proposal summary: 

A healthy, balanced diet is important for keeping metabolic health and supporting immune system. Obesity is associated with a wide range of metabolic syndromes, including dyslipidemia, hyperglycemia and fatty liver. Hyperglycemia and lipid accumulation may provoke lipid oxidation and further lead to an overproduction of cytokines, hyperactivation of complement system and activation of coagulation system, which all serve as immunological triggers to severe infection of COVID-19 as well as other infectious diseases. With the soaring prevalence of cardiometabolic diseases attributed to obesity and metabolic syndrome, the significance of dietary factors in this context is becoming increasingly emphasized. Mirroring the obesity pandemic in adults, paediatric obesity is also rapidly growing worldwide. As a consequence, metabolic dysfunction-associated steatolic liver disease (MASLD) has become the most common liver disease affecting children1. A concern about paediatric liver diseases is that the disease is likely to persistent into adulthood, conferring a substantial cumulative risk of progressing into chronic liver disease, as well as cardiometabolic dysfunction2. Beyond examining individual dietary components, such as fruits or red meat individually, the impact of overall dietary patterns during childhood on indicators of overall health outcomes, such as blood glucose levels, blood pressure, liver fat and chronic inflammation, in adolescence and early adulthood remain inadequately understood. Moreover, the advent of advanced omics technologies, such as metabolomics, provides a promising approach to elucidate the intricate mechanisms/pathways linking dietary patterns to health outcomes. In the current proposed project, we will explore all the potential associations between dietary patterns and immune response, as well as potential metabolic-related mediators to explain the observed associations between diet and immune response through mediation analysis in the ALSPAC study.

Impact of research: 
Date proposal received: 
Wednesday, 7 February, 2024
Date proposal approved: 
Tuesday, 20 February, 2024
Keywords: 
Epidemiology, Diabetes, Infection, Obesity, Computer simulations/modelling/algorithms, GWAS, Metabolomics, Proteomics, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cardiovascular, Genome wide association study, Liver function, Mendelian randomisation, Metabolic - metabolism, Nutrition - breast feeding, diet

B4534 - Measurement Invariance in predictors of dropout from cohort studies - 12/02/2024

B number: 
B4534
Principal applicant name: 
Gareth J Griffith | IEU
Co-applicants: 
Professor Kate Tilling, Professor Jon Heron
Title of project: 
Measurement Invariance in predictors of dropout from cohort studies
Proposal summary: 

Individuals who take part in voluntary studies provide valuable data for health scientists across a range of health-related outcomes. These studies are extremely useful for understanding relationships between health related exposures and health outcomes. Results from studies such as ALSPAC (Children of the 90s) often rely on statistical methods to apply such relationships to the wider population (as the people who take part in these studies are often unusual in some way). One of the most commonly used statistical methods for this is called weighting, where we statistically "up-weight" people who are less likely to take part in a study, and "down-weight" people who are more likely to take part in a study, so that we can apply our findings to populations which are dissimilar to the studied (ALSPAC) population. It is not well understood how these methods perform in cases where the weights are constructed from a complex measure such as mental health - which may be measured differently for people who remain in a study, and those who go on to drop out. This study will provide valuable insights into how we might approach this.

Impact of research: 
Methods Development around missing data, and consequences of non-random recruitment changes
Date proposal received: 
Monday, 5 February, 2024
Date proposal approved: 
Monday, 12 February, 2024
Keywords: 
Epidemiology, Mental health, Statistical methods, Social science

B4528 - Associations between mother-child interaction in infancy and depressive symptoms in adolescence - 13/02/2024

B number: 
B4528
Principal applicant name: 
Christian K. Tamnes | University of Oslo (Norway)
Co-applicants: 
Alexandra Havdahl, Lia Ferschmann, Christine Brita Mørtvedt Johnsen
Title of project: 
Associations between mother-child interaction in infancy and depressive symptoms in adolescence
Proposal summary: 

Mother-child interaction is an essential element in a child's development that is impacting children’s emotional and psychological well-being. This aspect of early relational dynamics is especially critical in understanding the development of depressive symptoms during adolescence. Despite its significance, current research on how early mother-child interactions influence the development of depressive symptoms in adolescents, particularly using longitudinal data, remains limited. Given the existing literature, a more nuanced exploration into how these early interactions shape mental health outcomes in adolescents is not only necessary but could be instrumental in developing early intervention strategies. Such interventions could potentially mitigate the development of depressive symptoms, thus contributing to healthier adolescent mental health.

Impact of research: 
Date proposal received: 
Friday, 2 February, 2024
Date proposal approved: 
Monday, 12 February, 2024
Keywords: 
Developmental Psychology, Mental health, Statistical methods, mother-child-interaction

B4539 - How does physical activity and body composition effect the risk of fracture in adults aged 30-60 - 21/02/2024

B number: 
B4539
Principal applicant name: 
Marcus Munafo | Integrated Epidemiology Unit
Co-applicants: 
Catherine Rolls, Emma Clark, Professor Helen Dawes
Title of project: 
How does physical activity and body composition effect the risk of fracture in adults aged 30-60?
Proposal summary: 

Background
Broken bones cause pain, disability, and time out of work in adulthood. Most of what we currently know about the causes of broken bones comes from research on children, adolescents, and the elderly. Little is known about what contributes to the risk of broken bones in people through mid-life.

This project will focus on how different levels of physical activity and body composition, i.e. bone strength and weight, may change the risk of a broken bone in people from early adulthood to mid-life (age 30-60).

Your approach
I will use data collected from large groups of people over many years, including the UK Biobank and the Avon Longitudinal Study of Parents and Children. These data sets have measures of physical activity, obesity, bone fragility and individual genetic data, as well as information on the outcomes of broken bones in adults aged 30-60. I will use classic epidemiology techniques and recent genetically-informed approaches to better understand the complex relationships between physical activity, body composition and broken bones.

Expected impact
Better understanding of the causes of broken bones in middle-aged adults will enable early targeted preventative strategies and hope to reduce the burden of fractures in later life.

Impact of research: 
Fractures are a major public health concern. This research aims to provide new incites into the the role of physical activity as both a risk factor and potential treatment strategy for adults who are not osteoporotic.
Date proposal received: 
Monday, 12 February, 2024
Date proposal approved: 
Monday, 12 February, 2024
Keywords: 
Epidemiology, Bone disorders - arthritis, osteoporosis, Computer simulations/modelling/algorithms, Bones (and joints)

B4527 - Inflammation and related metabolic and hormonal biomarkers for depression and other psychiatric conditions - 21/02/2024

B number: 
B4527
Principal applicant name: 
Golam Khandaker | University of Bristol (UK)
Co-applicants: 
Mr Timothy Larsen, Dr Christina Dardani, Prof Gibran Hemani
Title of project: 
Inflammation and related metabolic and hormonal biomarkers for depression and other psychiatric conditions
Proposal summary: 

What is the project about?
Immunometabolic dysfunction is implicated in depression and other psychiatric disorders, which may moderate the effect of antidepressant treatment. Existing case-control studies show changes in various blood immunometabolic biomarkers in depression, psychosis and other psychiatric disorders compared with controls, but longitudinal studies needed to assess temporality of association is scarce. Existing studies have almost exclusively used circulating blood biomarker levels as exposure which is informative, but does not reflect activity of the biomarker at cellular level accurately. Therefore, there is a need for developing novel measures reflecting biomarker activity/signalling more accurately to better understand the role of inflammation in psychiatric conditions.

My project will address these key issues using: i) longitudinal analysis testing the relationship of blood immunometabolic and related biomarkers with depression and other psychiatric outcomes; ii) develop and implement novel measures of activity/signalling of specific biomarkers (namely, interleukin 6 or IL-6, renin-angiotensin system or RAS) in analyses testing their associations with blood biomarkers and psychiatric outcomes.

Why is the project important?
Depression is a global public health concern, with recent research suggesting that it affects around 1 in 6 people in the UK. About 1 in 3 people with depression do not respond to currently available medications suggesting other mechanisms are involved. Demonstrating prospective associations of blood immunometabolic biomarkers with depression will strengthen causal inference and identify specific biomarkers for future investigation. Demonstrating how the activity of specific depression related biomarkers (e.g., IL-6 signalling) relates to depression risk will highlight specific pathways for intervention.

What do we know already?
While it is known that abnormal functioning of neurotransmitters such as serotonin are associated with depression, there is emerging evidence to suggest that inflammation may play a key role in its development. Studies have shown that individuals with major depressive disorder (MDD) have increased levels of interleukin 6 (IL-6) in the blood than healthy controls. Mendelian randomisation studies suggest a potential causal effect of IL-6 on depression and schizophrenia. However, which particular IL-6 signalling pathway underlies these associations remain unclear.

Impact of research: 
The proposed population-based studies would provide vital evidence on whether inflammation causally influences depression by addressing key issues of reverse causality and residual confounding. The proposed work is also relevant for other psychiatric disorders where inflammation may play a key role in the development of the condition. Where a role of inflammation is involved in the condition, this information can then be used to develop different treatment options.
Date proposal received: 
Friday, 2 February, 2024
Date proposal approved: 
Monday, 12 February, 2024
Keywords: 
Epidemiology, Mental health, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4525 - Maternal health and offpsrings bone health - 26/02/2024

B number: 
B4525
Principal applicant name: 
Lieke Elisabeth Johanna Maria Scheepers | University of Tasmania (Australia)
Co-applicants: 
Michael Thompson, MD and PhD, Bella Halim, MD
Title of project: 
Maternal health and offpsring's bone health
Proposal summary: 

Osteoporosis is a condition that causes bones to become fragile and more likely to fracture, even as a results of a minor bump or accident. The amount of bone accumulated from birth to young adulthood is the most important predictor of osteoporosis. Several factors influence the accrual of bone mineral during childhood and adolescence, including heredity, diet, physical activity, and endocrine status. It is postulated that risk of poor bone health may be programmed as early as in the intrauterine period. Maternal diet, exercise, and smoking, along with maternal health conditions like hypertension, diabetes, asthma, anaemia, and renal diseases, might affect fetal growth, development, and bone mineral acquisition. In vivo study showed that maternal glucose control of diabetic mother as can impact the skeletal growth and long-term bone health of their offspring.
The present study will be the first to assess the association between maternal diabetes, including pre-existing and gestational diabetes, and offspring’s bone health. Our study will provide compelling evidence as to whether maternal diabetes is associated with measures of bone health in children and young adolescence.

Impact of research: 
This study will provide compelling evidence on whether diabetes during pregnancy might be associated with offspring’s bone health outcomes. As we are the first, our study needs further replication in other pregnancy cohorts before it has any clinical implications.
Date proposal received: 
Tuesday, 30 January, 2024
Date proposal approved: 
Monday, 12 February, 2024
Keywords: 
Epidemiology, Bone disorders - arthritis, osteoporosis, Diabetes, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Bones (and joints), Growth, Mothers - maternal age, menopause, obstetrics, Offspring

B4521 - Investigating the associations between asthma and anxiety/depression - 12/02/2024

B number: 
B4521
Principal applicant name: 
James Dodd | University of Bristol/North Bristol NHS Trust
Co-applicants: 
Dr George Nava, Dr Christina Dardani, Prof Golam Khandaker
Title of project: 
Investigating the associations between asthma and anxiety/depression.
Proposal summary: 

Asthma is the most common long-term condition among children and young people in the UK, with over one million children currently receiving treatment for it.

People with asthma often experience anxiety and depression. We do not fully understand the link between all these conditions. We also don’t know if the relationship between them is causal (having one condition causes the other to develop).

Project aims

We want to identify whether there is a link between asthma and mental health disorders. We will do this by using data from the Avon Longitudinal Study of Parents and Children (ALSPAC).

ALSPAC is an ongoing study looking at the health of children born to mothers living in a specific part of England in the 90s. The original study has since expanded to include the next generation of children and their families.

We will use the large volume of data available through ALSPAC to explore the links between being diagnosed with asthma as a child and the likelihood of developing anxiety and depression. We will also look at the reverse, ie. whether having anxiety and depression as a child increases your likelihood of later being diagnosed with asthma.

What we hope to achieve

Findings from this study could support the development of clinical trials targeting patients with asthma and anxiety/depression. In turn, this could improve how people living with asthma manage their condition, reduce the number of exacerbations they experience and decrease the number of times they admitted into hospital.

This research is part of a PhD project and is being led by Dr George Nava. It is a collaboration between the respiratory and mental health themes of the Bristol BRC.

Impact of research: 
The results of this study could support the development of clinical trials targetting patients with asthma and comorbid anxiety/depression thereby improving asthma control, reducing exacerbations reducing admission to hospital and harm.
Date proposal received: 
Wednesday, 31 January, 2024
Date proposal approved: 
Monday, 12 February, 2024
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods

B4529 - Health effects of diet in young children - 06/02/2024

B number: 
B4529
Principal applicant name: 
Geraldine McNeill | University of Edinburgh (United Kingdom)
Co-applicants: 
Dr Alexa Bellows, Dr. Amelia Finaret, Dr Leone Craig, Prof Kate Northstone
Title of project: 
Health effects of diet in young children.
Proposal summary: 

What young children eat can affect their well-being in many ways, and the wide range of food choices and the rising cost of food can make it difficult for parents and carers to choose the best options for their children. The aim of this project is to find out how young children’s diet affects their growth and health as they develop into adults. For example, are children who have more sugary snacks and drinks more likely to be affected by tooth decay or overweight and high blood pressure later in life? Do children who follow a mostly plant-based diet get the right amount of nutrients such as protein for ideal growth? These questions come from a recent UK government review of the gaps in our knowledge on young children’s diets. We will discuss these questions with parents to find out what else they would like us to find out about feeding their children well.
To answer the questions raised we will use information on the diets of pre-school children from two up-to-date national surveys. The National Diet and Nutrition Survey (NDNS) collects information on all foods and drinks consumed over two days as well as the height and weight of children across the UK. Around 1,200 1-5 year-olds are expected to take part between 2019 and 2025. In addition, in 2024 the survey of Diet in Scotland’s children (DISH) will collect information on what around 300 children aged 2-5 years eat and drink and some further questions about their general food habits and household food situation. These surveys will tell us how different types of diets and food choices can provide enough nutrients for health and growth.
To find out how diet in young children affects longer-term growth and health we will use information from the Avon Longitudinal Study of Parents and Children (ALSPAC), a Bristol-based study of 14,000 children born in 1991-2 and their parents who contributed information on the children’s diet and health regularly over the last 30 years. This study will allow us to look at how diet in children under five is related to dental, heart, and lung health when they become young adults. By comparing the diet of young children in ALSPAC with the diet of children in the NDNS and DISH surveys we will be able to assess the changes in children’s diet across the last 30 years.
Studies from around the world have suggested that young children’s diets affect their health throughout their life. This project is designed to provide insights into the importance of these issues in the UK. This will help those who design the programmes and guidance which support all parents and carers to feed their children well.

Impact of research: 
The analysis will inform questions raised by the UK Scientific Advisory Committee on Nutrition (SACN). Representatives of DHSC will be monitoring the project progress and work plan si that the final report will be able to inform SACN's guidance on feeding of infants and young children in the future.
Date proposal received: 
Friday, 2 February, 2024
Date proposal approved: 
Tuesday, 6 February, 2024
Keywords: 
Epidemiology, Diabetes, hypertension, obesity, respiratory, cardiovascular disease, dental caries, Statistical methods, Biomarkers Blood pressure, BMI, bones, cardiovascular, development, dental, growth, nutrition,

B4526 - THE PLACENTA IN MATERNAL AND FETAL CARDIOVASCULAR HEALTH AND DISEASE - 12/02/2024

B number: 
B4526
Principal applicant name: 
Abigail Fraser | MRC IEU (United Kingdom)
Co-applicants: 
Prof DA Lawlor, Dr Carolina Borges, Dr S Ring, Dr Alix Groom
Title of project: 
THE PLACENTA IN MATERNAL AND FETAL CARDIOVASCULAR HEALTH AND DISEASE
Proposal summary: 

The placenta is the crucial interface between mother and developing fetus during pregnancy, enabling exchange of nutrients, oxygen, and waste products. The placenta is essential for a healthy pregnancy; placental pathologies underlie some of the most common pregnancy complications, referred to as placental syndromes (PS). PS include hypertensive disorders of pregnancy (preeclampsia and gestational hypertension), fetal growth restriction, and preterm delivery, which are leading causes of maternal and neonatal mortality and morbidity. PS are associated with adverse cardiovascular health beyond delivery and throughout life, both in the mother and offspring. Yet the placenta remain understudied and the mechanisms linking PS, congenital heart disease in offspring and cardiovascular health in both mothers and offspring are not well understood. In this project we aim to understand the the basis for primary placental disorders as the cause of secondary heart and vascular disease, both in the offspring and in the mother.

Impact of research: 
A step change in our understanding of the mechanism of PS and their links with cardiovascular health.
Date proposal received: 
Wednesday, 31 January, 2024
Date proposal approved: 
Monday, 5 February, 2024
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, RNA, Biological samples -e.g. blood, cell lines, saliva, etc., Birth outcomes, Blood pressure, BMI, Cardiovascular, Epigenetics, Expression, Genetic epidemiology, Genetics, Genome wide association study

B4452 - Associations between Early-life Modifiable Exposures with Biological Age of Offspring Multi-omics Analysis of ALSPAC - 13/02/2024

B number: 
B4452
Principal applicant name: 
Yang Zhao | Nanjing Medical University (China)
Co-applicants: 
Dr. Yuntao Chen, Dr. Dongfang You, Dr. Liya Liu, Dr Ruyang Zhang, Dr Sipeng Shen, Dr Jianling Bai, Dr. Yingdan Tang, Dr. Yaqian Wu
Title of project: 
Associations between Early-life Modifiable Exposures with Biological Age of Offspring: Multi-omics Analysis of ALSPAC
Proposal summary: 

Biological age, of which the calculation primarily involves the use of epigenomic data, such as methylation, could predict the health status and disease risk in humans, and show substantial differences between individuals in early life, sometimes even from birth. Numerous studies have demonstrated that accelerated biological ages were related to increased disease risk and mortality, whereas conversely, deceleration relates to better health and longevity.
The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that the health and disease risk of offspring could be influenced by exposures during parental pregnancy and early-life experiences. Current research also indicates that parental lifestyle and environmental exposures during early fetal development may have profound and lasting effects on the health of offspring. However, there are still gaps in our understanding of whether and how early-life modifiable exposures during parental pregnancy and early life, such as socioeconomic factors, education, etc., may impact the biological age of offspring, thereby influencing disease risk.
This project aims to investigate the causal relationship between early-life modifiable exposures with the biological age and the disease risk of offspring using data from the ALSPAC cohort. We will employ a multi-omics approach and longitudinal data analysis to explore the underlying biological mechanisms, providing new opportunities and valuable guidance for early detection and health interventions.

Impact of research: 
We will utilize Mendelian randomization, mediation analysis, and machine learning techniques to explore the causal relationships between modifiable exposures during parental pregnancy and early-life experiences and the biological age of offspring, as well as the prediction of offspring's disease risk. We anticipate that our study will identify factors in early-life exposures that accelerate the biological age of offspring and elucidate the causal mechanisms in affecting offspring's disease risk. This research will contribute to our understanding of the mechanisms by which early-life influences affect offspring health and will help identify potential modifiable intervention targets from early parental life stages to promote the health of offspring and reduce disease risk.
Date proposal received: 
Tuesday, 30 January, 2024
Date proposal approved: 
Monday, 5 February, 2024
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Biological age and Aging, Statistical methods, Aging, Environment, Epigenetics, Fathers, Genetic Epidemiology, Mother, Offspring

B4500 - The additional effect of paternal mental health on early childhood neurodevelopment - 31/01/2024

B number: 
B4500
Principal applicant name: 
catharina hartman | Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE) (Nederland)
Co-applicants: 
Dr. Eva Corpeleijn , dr. Marlou L.A. de Kroon, Mr. Gireesh K. Subbiah, Dr. Josue Almansa
Title of project: 
The additional effect of paternal mental health on early childhood neurodevelopment
Proposal summary: 

Accumulating data from epidemiological and molecular studies indicate that adverse early childhood neurodevelopment is a risk factor of neuropsychiatric illness in later life. Among several factors that can affect early childhood neurodevelopment, maternal health, including both her physical and mental health, have been convincingly identified as predictors of children’s neurodevelopment. However, the evidence concerning the additional effect of paternal mental health on the child`s neurodevelopment is sparse warranting further research in this area. This research fits in the Paternal Origins of Health and Disease concept (POHAD).

Impact of research: 
The findings from our study will provide insights to health professionals and policy makers into the potential impact of paternal mental health on early child (neuro) development (in addition to impact of maternal mental health).
Date proposal received: 
Sunday, 24 December, 2023
Date proposal approved: 
Wednesday, 31 January, 2024
Keywords: 
Epidemiology, It seems that I can only chose one condition in the system, therefore listed here: antisocial behaviour, cognitive impairment, risk behaviour, disorders – autism mental health - e.g. anxiety, depression, psychosis, Speech/language problems, Statistical methods, It seems that I can only chose one condition in the system, therefore listed here: Childhood - childcare, childhood adversity Cognition - cognitive function Communication (including non-verbal), Speech and language, Statistical methods.

B4513 - International Multicohort Pediatric Biomarker Collaboration Biomarkers4Pediatrics - 12/02/2024

B number: 
B4513
Principal applicant name: 
Iris Pigeot-Kübler | Leibniz-Institute for Prevention Research and Epidemiology - BIPS (Germany)
Co-applicants: 
Dr Steffen Dreger, Dr Timm Intemann, Dr Maike Wolters, Dr Khalid Iqbal, Prof Krasimira Aleksandrova, PD Dr Antje Hebestreit
Title of project: 
International Multicohort Pediatric Biomarker Collaboration (Biomarkers4Pediatrics)
Proposal summary: 

Health monitoring and clinical decision making in paediatric care largely depend on the availability of reference values for clinical parameters. Hence, the diagnosis of highly prevalent conditions in children and adolescents such as metabolic dysfunction has been hampered by the lack of a worldwide consensus on diagnostic criteria, as definitions and cut-offs being used in the paediatric population are frequently derived from the adult population. Providing globally applicable reference curves for the metabolic syndrome and its components, in early life - from birth to adolescence - represents a big step towards the ultimate goal: developing cut-offs for clinically relevant biomarkers for paediatric practice. By making use of the increasing availability of research data worldwide, we aim to establish a global pooling initiative building on a previously published special issue of the International Journal of Obesity "Filling the gap: international reference values for health care in children" (edited by Ahrens W, Moreno LA, Pigeot I), and further taking advantage of increased statistical power and variations across age groups, geographical regions and socio-cultural backgrounds. Thus, biomarker data for the metabolic syndrome are being collected, subsequently calibrated, harmonized, combined and analysed to provide age-, sex- and ethnic-specific reference curves for metabolic biomarkers to facilitate the diagnosis of metabolic syndrome in early life globally.

Impact of research: 
We aim to develop age-, sex- and ethnic-specific cut-offs for metabolic biomarkers to facilitate the diagnosis of metabolic syndrome in early life in clinical practice and public health.
Date proposal received: 
Tuesday, 16 January, 2024
Date proposal approved: 
Tuesday, 30 January, 2024
Keywords: 
Epidemiology, Diabetes, Hypertension, Obesity, Metabolic Syndrome, Computer simulations/modelling/algorithms, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Development, Metabolic - metabolism

B4514 - Urban exposome and body mass index trajectories from birth to adolescence - 06/02/2024

B number: 
B4514
Principal applicant name: 
Martine Vrijheid | ISGlobal (Spain)
Co-applicants: 
Dr. Tom Ranger, Sandra Márquez
Title of project: 
Urban exposome and body mass index trajectories from birth to adolescence
Proposal summary: 

This project will investigate whether the environment in which children live affects their likelihood of becoming overweight or obese as they grow up.

There is evidence that some factors of the urban environment, such as air pollution and whether the street design encourages walking, are linked to body mass index in children. There is a need to build on this evidence though, by considering how different factors might interact with each other, for example if a person lives near a busy road they will be exposed to noise and air pollution from it, so it is important to determine whether these factors are both related to body mass index, or whether it is one or the other. We will also investigate whether characteristics of individual people, like age and socio-economic status, affect the relationships found in previous studies.

This project will use height and weight measurements collected from children in the ALSPAC study and combine them with information on the environment in which they live, for example air pollutant levels, the amount of green and blue space, and the amount of public transport. We will use this information to determine whether the environment in which a child grows up affects their likelihood of becoming overweight or obese in later life, and also whether there are interactions between these factors. Understanding how these factors might affect overweight and obesity in childhood, and how it progresses into adolescence, is important for identifying communities that may be at increased risk, and to provide information that local communities may wish to use to address any relevant risk factors.

Impact of research: 
We aim to publish at least one peer-reviewed journal article and distribute our findings more broadly through "The conversation" style pieces. We hope these findings will inform the development and re-development of urban areas to maximise health outcomes for children and young people.
Date proposal received: 
Tuesday, 16 January, 2024
Date proposal approved: 
Monday, 29 January, 2024
Keywords: 
Epidemiology, Obesity, Statistical methods, Environment - enviromental exposure, pollution

B4517 - Early metabolic and proteomic features of endometrial cancer - 22/01/2024

B number: 
B4517
Principal applicant name: 
Vanessa Tan | MRC-IEU
Co-applicants: 
Professor Nicholas J. Timpson
Title of project: 
Early metabolic and proteomic features of endometrial cancer
Proposal summary: 

Cancers develop for many years before they are diagnosed. Using data from first-generation ALSPAC offspring, we aim in this study to estimate the effects of being more genetically susceptible to endometrial cancer on metabolic and proteomic traits measured in blood across early life; this should help to reveal what early stages of endometrial cancer development look like and when they occur. More specifically, we will examine associations of genetic risk scores for endometrial cancer that has been shown to be influenced by obesity with traits from targeted metabolomics measured in childhood (age 8y), adolescence (age 15y), and young adulthood (age 18y and 24y) and proteomics measured in childhood (age 8 y) and young adulthood (age 24). This allows us to view subtle changes in the circulating metabolome and proteome over time which precede the onset of clinically detectable endometrial cancer by several decades. Recognizing the early signs of endometrial cancer development is vital for informing early detection, preventing its onset in older age, and improving survival.

Impact of research: 
The likely output of this research will be at least one publication in a general medical or epidemiology journal, the impact of which may be theoretical advancement in active research fields of metabolism and cancer, and recommendations for clinical practice.
Date proposal received: 
Thursday, 18 January, 2024
Date proposal approved: 
Monday, 22 January, 2024
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Cancer, Metabolomics, NMR, Proteomics, Mendelian randomisation

B4520 - Genetics of anorexia nervosa and associations with physical and psychological dimensions of childhood development - 22/01/2024

B number: 
B4520
Principal applicant name: 
Jessica Dennis | University of British Columbia (Canada)
Co-applicants: 
Karanvir Singh, Graham Boucher
Title of project: 
Genetics of anorexia nervosa and associations with physical and psychological dimensions of childhood development
Proposal summary: 

Anorexia nervosa (AN) has the highest mortality out of all psychiatric conditions, early onset (between 12-15 years), and long-term health issues. Although the exact cause of AN is not yet fully understood, it is known that a complex combination of environmental and genetic factors plays a role in its development. Genetics alone are estimated to explain 50 to 60% of risk for AN. Recently, a large-scale genome-wide association study (GWAS) identified eight genomic regions associated with AN, as well as evidence that the genetic architecture of AN overlaps that of metabolic and anthropometric traits, such as body-mass index (BMI) and risk for type-2 diabetes. In this study, we will analyze AN GWAS results to compute polygenic risk scores (PRS) for ALSPAC participants, allowing us to estimate the genetic risk for AN for each participant. We will test how genetic risk for AN is associated with behavioural and emotional problems during childhood and whether these associations are development-specific by modeling psychopathology measures longitudinally. We will also test associations between AN and physical growth during early life. Given the patterns of genetic associations between AN and BMI, we will test whether genetic risk for AN that has been adjusted for genetic correlations with BMI affects previously identified associations.

Impact of research: 
We will describe how genetic risk for AN is associated with early life development. This will further elucidate the role that genetics play in the development of the condition. It will highlight how children carrying a high genetic risk for anorexia nervosa develop, years before condition-specific symptoms can be detected. This will deepen our understanding of the pathophysiology of AN.
Date proposal received: 
Saturday, 20 January, 2024
Date proposal approved: 
Monday, 22 January, 2024
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Eating disorders - anorexia, bulimia, Mental health, Gene mapping, GWAS, Statistical methods, BMI, Development, Genetic epidemiology, Genome wide association study, Growth, Psychology - personality

B4519 - UKLLC Investigating the association of long-term air pollution exposure with risk and severity of SARS-CoV-2 infection - 22/01/2024

B number: 
B4519
Principal applicant name: 
Annalan Mathew Dwight Navaratnam | University of Cambridge
Co-applicants: 
Title of project: 
UKLLC: Investigating the association of long-term air pollution exposure with risk and severity of SARS-CoV-2 infection
Proposal summary: 

Information can be obtained from ALSPAC (B number folder) or the UK LLC on request

Impact of research: 
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
Date proposal received: 
Friday, 19 January, 2024
Date proposal approved: 
Monday, 22 January, 2024
Keywords: 
Epidemiology, Respiratory - asthma, Environment - enviromental exposure, pollution

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