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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B4440 - DNA methylation profiles in children in relation to pre- and postnatal exposure to environmental noise LongITools - 25/10/2023

B number: 
B4440
Principal applicant name: 
Ana Goncalves Soares | University of Bristol (United Kingdom)
Co-applicants: 
Kimberley Burrows
Title of project: 
DNA methylation profiles in children in relation to pre- and postnatal exposure to environmental noise (LongITools)
Proposal summary: 

This project will investigate the association between noise exposure during pregnancy and DNA methylation in children

Impact of research: 
Date proposal received: 
Thursday, 19 October, 2023
Date proposal approved: 
Monday, 23 October, 2023
Keywords: 
Molecular genetics and genomics, Environmental epidemiology, DNA sequencing, Epigenetics

B4431 - Diastolic blood pressure across the life course risk factors and consequences - 19/10/2023

B number: 
B4431
Principal applicant name: 
Laura Howe | MRC IEU
Co-applicants: 
Prof Abigail Fraser, Vandana Venkat
Title of project: 
Diastolic blood pressure across the life course, risk factors and consequences
Proposal summary: 

High blood pressure is a risk factor for heart disease. Most research is carried out using systolic diastolic pressure - the pressure in the heart when the heart muscle contracts. Less is known about diastolic blood pressure - the pressure in the heart when the heart muscle relaxes. This project seeks to better understand diastolic blood pressure - what influences is, and what are its consequences for heart health.

Impact of research: 
Improved understanding of diastolic blood pressure
Date proposal received: 
Thursday, 5 October, 2023
Date proposal approved: 
Thursday, 19 October, 2023
Keywords: 
Epidemiology, Blood pressure

B4425 - Menopause and depression assessing causation and identifying mechanisms - 10/10/2023

B number: 
B4425
Principal applicant name: 
Carol Joinson | Population Health Sciences, Bristol Medical School (UK)
Co-applicants: 
Ms Rochelle Knight, Prof Abigail Fraser, Dr Ana Goncalves Soares
Title of project: 
Menopause and depression: assessing causation and identifying mechanisms
Proposal summary: 

Despite the increasing media coverage concerning the impacts of the menopause on women’s mental health, this remains an under-researched area. Menopause affects quality of life, work, and relationships and is also a period of increased risk of depression. Depressive symptoms during menopause are often attributed to hormonal changes, but life stressors that coincide with the menopausal transition could also have a depressogenic effect. Earlier research, based mainly on cross-sectional data, has found that a later age at menopause and a longer reproductive period are associated with a lower risk of depression. This may reflect a greater lifetime exposure to oestrogen, which is thought to have an antidepressant effect in women. Limitations of previous studies include inadequate adjustment for confounders; lack of control for premenopausal depression, and failure to account for other factors affecting lifetime oestrogen exposure (e.g. oral contraceptives, breastfeeding, number of pregnancies) or hormone replacement therapy. Very few studies have sought to uncover the biopsychosocial mechanisms that might explain increased levels of depression during the menopausal transition. This project aims to advance understanding of women’s mental health during menopause by applying cutting edge causal inference methods.

Impact of research: 
This aim of this project is to advance understanding of women’s mental health during menopause by applying cutting edge causal inference methods, and potentially provide new insights into translational targets for interventions. This is a PhD project so research will aim to be published throughout the course of the PhD. Scripts and code will be published on Github to allow for public use. All scientific manuscripts generated from the research will be published on open-access platforms such as Wellcome Open Research or medRxiv. Presentations will be given throughout the PhD to disseminate findings to academic colleagues, at conferences and to the public.
Date proposal received: 
Friday, 29 September, 2023
Date proposal approved: 
Tuesday, 10 October, 2023
Keywords: 
Epidemiology, Mental health, Statistical methods, Mothers - maternal age, menopause, obstetrics

B4426 - Investigating factors associated with within-individual variability in BMI from childhood through to early adulthood - 09/10/2023

B number: 
B4426
Principal applicant name: 
Richard Parker | University of Bristol
Co-applicants: 
Prof. Kate Tilling, Dr Amanda Hughes, Ka Kei Sum
Title of project: 
Investigating factors associated with within-individual variability in BMI from childhood through to early adulthood
Proposal summary: 

Much research has indicated that obesity is associated with poorer health outcomes. Whilst these studies have tended to investigate average body weight (relative to height), more recently there has been interest in variation in body weight. This work has indicated that people whose body weight goes up and down a lot are more likely to experience future weight gain. This project will investigate variability in weight, using body mass index (BMI, a measure of weight which accounts for height), across the key developmental phase of childhood through to early adulthood. It aims to form a better understanding of the factors associated with variability in BMI across this time.

Impact of research: 
Better understanding of the factors associated with within-individual variability in BMI over childhood and early adulthood could provide insight into this phenotype across this key developmental phase, beyond a characterisation of its mean level.
Date proposal received: 
Monday, 2 October, 2023
Date proposal approved: 
Monday, 9 October, 2023
Keywords: 
Epidemiology, Eating disorders - anorexia, bulimia, Obesity, Statistical methods, Statistical methods

B4422 - A multi-cohort analysis of interacting prenatal and genomic risks in the development of childhood ADHD - 09/10/2023

B number: 
B4422
Principal applicant name: 
Ashley Wazana | McGill University
Co-applicants: 
Laurie Haig, Researcher, Eszter Szekely, Co-PI, Francois Freddy-Ateba, Co-Invetigator
Title of project: 
A multi-cohort analysis of interacting prenatal and genomic risks in the development of childhood ADHD
Proposal summary: 

Attention deficit hyperactivity disorder (ADHD) is the most common mental disorder in children worldwide, and can have lifelong health impacts, making it a major public health issue. Rates of ADHD have been increasing in Canada in recent years, particularly in Quebec, and increasing attention has been given to ADHD diagnosis around the world. Previous research suggests there is a significant gender gap in ADHD in children, with boys much more likely to be diagnosed than girls. However, reasons for this difference remain largely unknown. Genetic factors are known to play a key role in the development of ADHD. Yet, genes do not act in isolation. The early environment can also strongly influence brain development and may modify the risk of ADHD. Specifically, maternal stress may alter the prenatal environment to increase the risk of developing ADHD, which may be more likely to impact males due to genetic sex differences. The proposed research aims to analyze the relationship between prenatal maternal stress and offspring sex and genes in relation to the risk of later ADHD diagnosis. This analysis will be carried out in four large independent prenatal cohorts from Canada, the UK (ALSPAC), the Netherlands, and Singapore. Through the use of international, longitudinal data, the proposed project will be able to unpack the complex mechanisms that can result in the development of ADHD across different cohorts and settings. This will lead to a better understanding of the relevant genetic and environmental determinants of ADHD, to allow for better treatment options and identify potential areas of early intervention.

Impact of research: 
This research will be able to create a more complete theoretical model for the determinants of ADHD. The findings of this research will be reported in one manuscript which will be included as a part of the thesis submission and submitted for publication. Such a model will have important implications given the lifelong impacts of this disorder globally. A better understanding of the complex interplay between polygenic, environmental, and sex-related factors underlying ADHD can inform the development of more effective interventions, both early and preventative.
Date proposal received: 
Thursday, 5 October, 2023
Date proposal approved: 
Monday, 9 October, 2023
Keywords: 
Epidemiology, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Genetic epidemiology, Genetics, Sex differences

B4392 - Genetic risk scores for increased levels of endocrine disruptors and pubertal timing - 06/10/2023

B number: 
B4392
Principal applicant name: 
Despoina Manousaki | Research Center of the CHU Sainte-Justine (Canada)
Co-applicants: 
Melody Zuo, Kaossarath Fagbemi
Title of project: 
Genetic risk scores for increased levels of endocrine disruptors and pubertal timing
Proposal summary: 

Puberty is defined as the transition from infancy to reproductive maturity characterized by the acceleration of growth velocity and the development of secondary sexual characteristics and genitals. Normal puberty onset ranges between 8-13 years old for girls, and 9-14 years old for boys. It is clinically defined as the onset of Tanner stage 2 in thelarche for girls (development of breast buds) and by Tanner stage 2 in external genitalia development for boys (increase in testicular volume to >4mL). Age at menarche in girls and age at peak height velocity in both sexes are landmarks which can be used to evaluate pubertal timing.

Endocrine disrupting chemicals (EDCs) have become increasingly prevalent in the past century as manmade products and chemicals have been made essential in our daily lives. There are nearly 85 000 human-made chemicals in the world, and 1000 or more of those could be endocrine disruptors. There are two main types of EDCs: the persistent organic compounds with decade-long half-lives such as dichloro-diphenyl-trichloroethane (DDT) in pesticides and polychlorinated biphenyls (PCBs), and those that have a shorter half-life but can cause long-term health consequences such as phthalates and bisphenol A. EDCs disrupt the body’s delicate endocrine homeostasis by acting as an agonist or antagonist when binding to hormone receptors, thereby causing unwanted effects, such as earlier timing of puberty in girls and boys. The four EDCs of interest in our study are dibutyl phthalate, bisphenol A (BPA), dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyl (PCB).

Phthalates are a large group of omnipresent compounds used as liquid plasticizers. They are found in food packaging, cosmetic products, shampoo, children’s toys and medical device tubing. It was found that first and second-trimester exposure to Bis(2-ethylhexyl) phthalate (DEHP) was associated with increased peripubertal serum estradiol levels, whereas third-trimester exposure was associated to a delay of pubarche onset. BPA is used to make polycarbonate plastic and epoxy resin. It can be found in food packaging, toys, and canned beverages’ linings. At low concentrations, BPA and other phenol compete with endogenous estrogens for binding, whereas at higher concentrations they have anti-androgenic properties.
DDT was used in many organochlorine pesticides and insecticides before being banned in 1972 in multiple countries. In 2006 however, it was reintroduced in some areas by the World Health Organization in order to fight malaria and control other vector-borne diseases. DDT exposure begins prenatally and lasts throughout a lifetime, as it is found in abundance in consumed food products, and is found to have anti-androgenic properties. PCBs were found in lubricants, electrical equipment and plasticizers up until they were banned in 1979. Studies show that childhood exposures of PCBs are associated with earlier pubertal milestones in boys, such as earlier Tanner stages.
Although a large body of evidence from observational studies exists linking EDCs to pubertal timing variations, these associations can be confounded by factors such as low socio-economic status and obesity and cannot establish causality. In the absence of evidence from randomized controlled trials- which would be unethical to employ, the causal link between EDCs and pubertal timing remains undetermined. We have generated preliminary results using two-sample Mendelian randomization for 19 EDCs, most of which do not support a causal association of genetically determined levels of these EDCs with age at menarche in girls or age at voice change or facial hair in boys. Using genetic variants associated with levels of these EDCs, which are not influenced by environmental confounders, we aim to investigate if genetic predisposition to higher levels of these chemicals could affect pubertal timing in ALSPAC children.
In the proposed project, we hypothesize that genetic risk scores (GRS) composed of one to multiple single nucleotide polymorphisms (SNPs) associated with levels of 19 endocrine disrupting chemicals (dibutyl phthalate, BPA, DDT and 16 types of PCBs) in the largest available genome-wide association studies for EDC levels, could be associated to an altered age at menarche in girls or age at peak height velocity in both girls and boys (adjusting for sex) with and without adjusting for BMI SDS at age 8 and socio-economic status.

Impact of research: 
This proposed study holds significant public health improvement potential, as, in combination of the results of our two-sample Mendelian randomization analyses, it will contribute to the understanding of the effect of EDCs on pubertal timing. EDCs are a fairly new threat to human health as they have only been on the rise in the past two centuries, therefore the health repercussions of many new chemicals have not yet been elucidated or understood. Identifying whether there are associations between specific EDCs and the hallmarks of puberty onset (age at menarche and peak height velocity) could contribute to public awareness about the consequences and inform public health policies. Additionally, taking into consideration the potential modifying effect of BMI and socio-economic status could help determine the relationship between early-life body adiposity and environment-related effects on puberty. These findings could further contribute to public health education about the importance of keeping a healthy lifestyle and a healthy BMI, especially in areas of lower socio-economic status that are more vulnerable to EDCs exposure and increased average BMI. Ultimately, the findings from this study could lead to evidence-based interventions aimed at reducing EDCs exposures during critical developmental periods in childhood, and increased awareness about the associations mediated between EDCs and puberty, which could enable better protection for the future generations and encourage other investigations on these topics.
Date proposal received: 
Friday, 4 August, 2023
Date proposal approved: 
Friday, 6 October, 2023
Keywords: 
Endocrinology, Puberty , GWAS, Endocrine - endocrine disrupters

B4424 - Causal inference in adverse childhood experiences research - 04/10/2023

B number: 
B4424
Principal applicant name: 
Laura Howe | MRC Integrative Epidemiology Unit at the University of Bristol (United Kingdom)
Co-applicants: 
Ka Kei Sum, Annie Herbert, Jon Heron
Title of project: 
Causal inference in adverse childhood experiences research
Proposal summary: 

Adverse Childhood Experiences (ACEs) include abuse and neglect, and measures of family dysfunction such as parental substance misuse, intimate partner violence, psychiatric disorders, and separation. People who experience ACEs are more likely to develop adverse health-related behaviours and poor physical and mental health.

There is increasing awareness of the role that adverse childhood experiences (ACEs) can play in influencing poor health-related behaviours, physical, and mental health. The definition of ACEs varies between studies, but the adversities most commonly studied include child maltreatment (e.g., emotional, physical, and sexual abuse; physical or emotional neglect) and measures of household dysfunction (e.g., violence between parents, parental separation and parental substance misuse, mental illness, or criminal behaviour).
ACEs are rising rapidly on policy agendas, and there is a drive within public health and other spheres of public policy to prevent ACEs, develop and implement interventions to support people who have experienced ACEs, promote ACE-aware services, and even to screen people for the number of ACEs they have encountered. The ACEs framework has led to considerable financial investment from the public sector.
ACEs are more common in people living in poverty. We also know that poverty, adversity, and poor health tend to pass down across the generations within a family. This means that if we simply look at the association between ACEs and health, without fully accounting for the broader family context, this may exaggerate the effect of ACEs on health. Yet this is exactly what is done in the majority of scientific research on ACEs. There are very few studies that try to look at whether ACEs actually cause poor health. If we really want to understand how ACEs are influencing health and use this information to design effective policies and interventions with scarce public resources, we need higher-quality evidence.

In this project, we will improve the quality of evidence on whether ACEs causally affect health by analysing data from ALSPAC, which has followed up children and their families across their lives. We will use information about health before and after an ACE has happened, to see whether the ACE led to a change in health, i.e. whether the ACE ‘derails’ someone from the health trajectory they were already on. We can also use information about other ACEs that happened earlier in life, or even ACEs that happened to the parents when they were children. We will look at whether ACEs influence health-related behaviours (smoking, alcohol use, drug use, and physical activity), physical health (obesity, and the health of the heart and lungs), and mental health.

Impact of research: 
Improved understanding of causality of the relationship between ACEs and health.
Date proposal received: 
Friday, 29 September, 2023
Date proposal approved: 
Wednesday, 4 October, 2023
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Obesity, BMI, Childhood - childcare, childhood adversity, Genetic epidemiology, Social science

B4418 - Data Note ALSPAC linked AWP data - 04/10/2023

B number: 
B4418
Principal applicant name: 
Mark Mumme | University of Bristol
Co-applicants: 
Dr Jon Heron, Dr Jasmine Raw
Title of project: 
Data Note ALSPAC linked AWP data
Proposal summary: 

A data note describing the linked data obtained by ALSPAC about the participants in ALSPAC held by AWP (Avon Wiltshire Partnership MH NHS Trust). This will describe the data available for future research.

Impact of research: 
Increase exposure of ALSPAC as a whole, and to promote research into MH using ALSPAC research assets.
Date proposal received: 
Thursday, 21 September, 2023
Date proposal approved: 
Wednesday, 4 October, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, descriptive, Mental Health

B4423 - Youth Vascular Consortium amendment to B3727 - 03/10/2023

B number: 
B4423
Principal applicant name: 
Monique Breslin | Menzies Institute for Medical Research (Australia)
Co-applicants: 
Vimarsha Kodithuwakku, Dr Rachel Climie, Dr Chloe Park
Title of project: 
Youth Vascular Consortium (amendment to B3727)
Proposal summary: 

Cardiovascular disease (CVD) is the leading
cause of death worldwide, accounting for nearly one-third of all deaths, and poses
a major economic burden to the global healthcare system. Thus, the prevention of
CVD is a public health priority and identifying individuals at increased
cardiovascular risk at an early stage is of paramount importance for minimising
disease progression.

Vascular ageing, the decline in vascular structure and function, is an integrated
marker of overall cardiovascular risk burden on the vasculature over time and
ultimately leads to end organ damage in the heart, brain and kidney. While age
dependent arterial damage typically appears in the fifth or sixth decade of life,
there is wide variability between individuals with some displaying early vascular
ageing. Exposure to environmental and genetic factors as early as during
childhood or even during foetal life promotes the development and accumulation of
subclinical vascular changes that directs an individual towards a trajectory of early
vascular ageing. This has led to the concept that vascular age, as opposed to
chronological age, may be better related to the prognosis of CVD.

However, research concerning vascular ageing in early life and/or adolescents is
sparse despite substantial evidence indicating that the formative years of life play
a significant role in contributing to traditional risk factors exhibited in adulthood.
It is unclear what is normal vascular ageing in this population and no large-scale
study has determined what specific factors contribute to accelerated vascular
ageing in early life.

By creating the Vascular Youth Consortium we will be able to address these
unknowns. The findings of which, will be instrumental to clinicians in preventing
the development of overt CVD later in life.

Impact of research: 
There are several expected outcomes from this consortium including: • The establishment of a collated databank containing study data from collaborators worldwide. • The establishment of reference values for vascular ageing in children, adolescents and young adults. • The identification of risk factors that contribute to early vascular ageing in the younger population. • The development of a predictive index of early vascular ageing in children, adolescents and young adults, based on identified risk factors. • A head-to-head comparison between different techniques used to determine vascular ageing in children, adolescents and young adults. The results of the consortium will be instrumental to clinicians in preventing the development of overt CVD later in life.
Date proposal received: 
Wednesday, 27 September, 2023
Date proposal approved: 
Tuesday, 3 October, 2023
Keywords: 
Physiology, Obesity, Medical imaging, Childhood - childcare, childhood adversity

B4420 - Examining the relationship between autism spectrum disorder and paediatric incontinence using a polygenic risk score and Mendeli - 26/09/2023

B number: 
B4420
Principal applicant name: 
Carol Joinson | PHS (United Kingdom)
Co-applicants: 
Dr Christina Dardani, Dr Kimberley Burrows, Mr Olly Bastiani
Title of project: 
Examining the relationship between autism spectrum disorder and paediatric incontinence using a polygenic risk score and Mendeli
Proposal summary: 

Autism spectrum disorder (ASD) is characterised by deficits in social interaction, communication, and language, as well as stereotyped and repetitive behaviours. There is strong evidence from observational studies for comorbidity between ASD and functional incontinence in children including enuresis (bedwetting), daytime urinary incontinence (DUI), and faecal incontinence (FI).

Impact of research: 
The findings have the potential to advance understanding of the link between autism and childhood incontinence and could inform clinicians about which children are at increased risk of problems attaining continence, and therefore target them for early interventions
Date proposal received: 
Monday, 25 September, 2023
Date proposal approved: 
Tuesday, 26 September, 2023
Keywords: 
Epidemiology, Incontinence, Statistical methods, Genetics

B4411 - Exploring maternal and fetal molecular mechanisms of and risk factors for congenital anomalies - 04/10/2023

B number: 
B4411
Principal applicant name: 
Amy Taylor | University of Bristol (United Kingdom)
Co-applicants: 
Professor Deborah Lawlor, Dr Carolina Borges
Title of project: 
Exploring maternal and fetal molecular mechanisms of and risk factors for congenital anomalies
Proposal summary: 

Congenital anomalies (CAs) occur during the intrauterine life and can be identified during pregnancy, at birth or later in life. CAs can be defined as structural (e.g. limb reduction defects) or functional (metabolic disorders). In European countries, CAs affect approximately 2–3% of births. Although consequences vary depending on the type and severity of the condition, CAs are a major cause of fetal death and infant morbidity. Each year, more than 3 million children under the age of 5 die from CAs globally. In addition, many children with CAs and their families experience lifelong complications.

Whilst multiple factors have been identified as causes of CAs, approximately 50% of congenital disorders cannot be linked to a specific cause . Therefore, there is a pressing need for research to identify modifiable causes of CAs. This project aims to explore genetic and molecular mechanisms of CAs as well as risk factors such as maternal lifestyle factors, health and medication use.

Impact of research: 
There are already several papers in progress from the initial MR-PREG analyses. This work will be important for identifying the mechanisms and causes of CAs.
Date proposal received: 
Monday, 25 September, 2023
Date proposal approved: 
Monday, 25 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Mendelian randomisation

B4419 - Investigating factors associated with within-individual variability in depressive symptoms from childhood through to early adult - 25/09/2023

B number: 
B4419
Principal applicant name: 
Richard Parker | University of Bristol
Co-applicants: 
Dr Gareth Griffith, Dr Jon Heron`, Dr Alex Kwong, Prof. Kate Tilling, Vandana Venkat
Title of project: 
Investigating factors associated with within-individual variability in depressive symptoms from childhood through to early adult
Proposal summary: 

People who have depression whilst they are adolescents are more likely to have depression, and other health problems, in later life. They are also more likely to face social and economic challenges. When measuring depression, it is usual to gauge the average levels of depressive symptoms, such as negative emotions, someone has: for example, are they high, or rising quite steeply? In addition, though, evidence suggests that how variable one’s mood is may also be important in predicting later health and other outcomes: for example, does someone’s mood fluctuate a lot, around these average levels? However, whilst a lot of research has been focused on trying to better understand average levels of mood, there have been far fewer studies exploring such variability in mood. This project aims to help address this, by focusing on variability in depressive symptoms from childhood through to early adulthood, with the aim of forming a fuller understanding of the development of depression, beyond average levels of symptoms.

Impact of research: 
Better understanding of the factors associated with within-individual variability in depressive symptoms over childhood and early adulthood could provide insight into the development of such symptoms, beyond a characterisation of their mean level.
Date proposal received: 
Thursday, 21 September, 2023
Date proposal approved: 
Monday, 25 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Depression

B4369 - Study of Prediction model for Preeclampsia - 21/09/2023

B number: 
B4369
Principal applicant name: 
Wang Bingshun | Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine
Co-applicants: 
Wang Xiaojin, He Yunjiang
Title of project: 
Study of Prediction model for Preeclampsia
Proposal summary: 

Preeclampsia poses significant risks to both mothers and babies. Many prediction models for preeclampsia have emerged in recent years. Using repeated measurements along with maternal factors has proven to be more effective in screening for preeclampsia than models that only consider maternal risk factors. However, traditional methods may introduce bias due to competitive events, and there is currently no preeclampsia prediction model in ALSPAC that considers competing-risk events.

Moreover, while numerous prediction models involve complex variables or models, cost-effectiveness must be taken into consideration. It is important to customize prediction models to local populations to effectively apply them. Relying on variables that are not available in local antenatal care can restrict their usefulness. It is suggested that localization should prioritize non-invasive indicators that are easily obtainable in clinical practice. An example of this is continuous blood pressure monitoring (CBP), which was recommended by the U.S. Preventive Services Task Force in 2017 as a PE screening method until a proven one is developed. However, it is not being utilized enough.

This project aims to develop a multivariate prediction model for preeclampsia by considering competing risk events and clinically accessible repeated measurements.
Before putting the prediction model into clinical practice, it will undergo essential validation across multiple datasets externally. The project’s benefits will be two-fold: first, shedding light on preeclampsia onset determinants in line with clinical practice, and second, improving the identification of women of high risk for preeclampsia.

Impact of research: 
This study aims to shed light on the causes of preeclampsia and aligns with clinical practice. It will also aid in identifying women who are at a higher risk of developing preeclampsia, ultimately improving their care.
Date proposal received: 
Saturday, 5 August, 2023
Date proposal approved: 
Thursday, 21 September, 2023
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Mothers - maternal age, menopause, obstetrics

B4417 - Evaluation of polygenic risk scores and development of integrated risk tools across the life course - 25/10/2023

B number: 
B4417
Principal applicant name: 
Vincent Plagnol | Genomics plc (United Kingdom)
Co-applicants: 
Rachel Moore, Jamie Floyd, Jamie Hall, Charlie Hatcher, Edward Beard, Sophie Landon, William Tarran, Deborah Thompson, Melisa Chuong, Daniel Wells
Title of project: 
Evaluation of polygenic risk scores and development of integrated risk tools across the life course
Proposal summary: 

Polygenic risk scores (PRSs) aggregate genetic data across the genome and summarise these data into a single number that quantifies an individual’s genetically defined disease risk. PRSs can also be used to predict standard outcomes that are relevant to health, such as height or weight. Genomics plc has built a range of tools to generate the most accurate PRS library, and combine these PRSs with other non-genetic factors into integrated risk tools (IRT). However, typical PRS and IRT evaluation focuses on adulthood. As a result, we have a limited understanding of how these tools perform across the life course, especially at which age genetically driven differences become apparent. Similarly, little is known of how the combination of PRS and early life data can jointly predict adult outcomes, which is key for preventative opportunities that need to occur at an early age.
ALSPAC has generated unique data across the life course of individuals. These data provide an opportunity to understand the interplay between childhood and adult data together with genetics. We therefore are proposing to use the ALSPAC data to understand the role of PRSs in the context of an individual life’s course, with a focus not only on prediction accuracy but also on how the accuracy of these predictions varies with age and when they have the greatest utility. We will further explore whether childhood information, together with immutable genetic data, can be combined to accurately predict traits in adulthood, thus providing an effective lever for triggering health interventions that are most useful during childhood.

Impact of research: 
We anticipate that this project will enable us to better quantify our predictions of health outcomes and trait values, with and without early life information. This information will improve our understanding of the contribution of the genetic information captured by PRS to risk/trait prediction at each stage of the life course, and will hence provide clarity around the potential benefits that could be conferred by the appropriate use of PRS at different points in an individual’s life.
Date proposal received: 
Monday, 18 September, 2023
Date proposal approved: 
Thursday, 21 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Bone disorders - arthritis, osteoporosis, Cancer, Diabetes, Eczema, Gastrointestinal, Hypertension, Infection, Obesity, Respiratory - asthma, General quantitative traits, such as weight, BMI, height, blood pressure , GWAS, Statistical methods, Polygenic risk scores, Blood pressure, BMI, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Metabolic - metabolism, Statistical methods

B4386 - Comparison between consumers of a high free sugars diet and those of a low free sugars diet 11-07-2023 - 150900 - 21/09/2023

B number: 
B4386
Principal applicant name: 
Caroline Taylor | Bristol Medical School (UK)
Co-applicants: 
Dr Pauline Emmett
Title of project: 
Comparison between consumers of a high free sugars diet and those of a low free sugars diet (11-07-2023 - 15:09:00)
Proposal summary: 

The current recommendation is to limit intake of free sugars to below 10% of energy (calories) but very few children achieve this. We will investigate free sugars intake in the diets of ALSPAC children at 7, 10 & 13 years of age. We will identify two groups of children, those who consume 20% or more of their energy from free sugars and those who consume less that 15% of their energy from free sugars at all three ages. These two groups will be compared for differences in food group and nutrients intakes. We will investigate their background diet and social differences to determine points where intervention could be made to improve children's diets.

Impact of research: 
To inform the development of evidence-based intervention to improve children's diets and therefore long-term health.
Date proposal received: 
Thursday, 14 September, 2023
Date proposal approved: 
Wednesday, 20 September, 2023
Keywords: 
Nutrition, Obesity, Statistical methods, Nutrition - breast feeding, diet

B4414 - ICARHE Improving Childrens cARdiovascular Health in a digitalised Europe - 21/09/2023

B number: 
B4414
Principal applicant name: 
Jean-Philippe Empana | The National Institute of Health and Medical Research (INSERM) (France)
Co-applicants: 
Prof Nicholas Timpson, Prof Kate Northstone
Title of project: 
ICARHE: Improving Children’s cARdiovascular Health in (a digitalised) Europe
Proposal summary: 

Despite major achievements in risk factor control (primary prevention) and clinical care (secondary prevention) over the last decades, cardiovascular disease (CVD) continue to have tremendous substantial societal impact affecting 6 million people and costing 210 billion euros each year in the European Union (EU).1 CVD has a profound negative impact on quality of life of affected individuals and has significant societal consequences including major costs and premature loss of the labor force.1 Projections are pessimistic given the global ageing population, obesity epidemic, high levels of physical inactivity and sedentary behavior, poor diet, increased health inequalities, and poor mental health. Added to this, the COVID-19 pandemic has exacerbated unhealthy behaviors, health inequalities and increased the burden of mental health especially among the young. CVD is preventable: 70 to 80% of CVD incidence has been attributed to behavioral risk factors such as smoking, poor diet and physical inactivity, that subsequently impacts weight gain, blood pressure, blood glucose and blood lipids. Therefore, preventing risk factors in the first place (i.e. primordial prevention) and promoting optimal cardiovascular health (CVH) across the life course may be a new and relevant strategy to prevent the incidence of CVD. Many CVD risk factors already occur in childhood, track into adulthood, and are predictors of fatal and non-fatal CVD events in adulthood. Furthermore, early life habits are the strongest predictors of later life habits. Taken together, programs that promote healthy habits among children and their families will likely have a lasting positive impact on adult (cardiovascular) health and therefore an important societal impact. In order for such programs to be effective, sustainable and scalable, including among socially disadvantaged groups, it is critical that a holistic and trans-disciplinary codesign approach is taken accounting for the contexts of children’s family, health literacy of the children’s family, children’s well-being, and contextual factors such as their place of residence, school environment, built environment (green space, recreational places for physical activities, food supply, noise exposure). Such programs should be designed to be responsive and easily implementable, ensuring the needs and rights of children and their families are accounted for. This can be achieved through authentic engagement with all stakeholders (beneficeries as well a service providers) in contemporary codesign in diverse contexts.

Project ambition
• To inform about contextual and individual determinants of CVH and the associated health outcomes in children & adolescents
Most studies in children and adolescents have evaluated the distribution of a single CVD risk factor, especially behavioral ones, at a specific age. The few studies that have addressed the distribution of multiple risk factors focused on behavior-related factors such as weight, physical activity, diet and more recently, sleep. In fact, only three small studies (n<500), conducted in the US and France, reported the distribution of the complete CVH score and examined the determinants of CVH in children. Importantly, none evaluated the possible health benefits associated with higher CVH.
SO1 has the ambition within one year , to rapidly inform the international scientific community and the relevant stakeholders from the EU member states on (i) the level of the CVH of European children and adolescents including those from socially disadvantaged backgrounds, (ii) the individual and contextual determinants of CVH, and (iii) the potential health benefit associated with higher CVH. This will be achieved by using harmonized and readily available birth cohort data from four diverse European countries already participating to the EU Child Cohort Network (n??). This will provide the first European evidence-based data to (i) inform the general public, scientific community and policy makers on the key drivers of CVH in children; (ii) estimate the long-term health and cost savings associated with higher CVH early in life and; (iii) support recommendations for primordial prevention implementation at school across Europe.
• To develop a digital solution to support the promotion of CVH in children
The widespread availability of smartphones, tablets, and computers has opened opportunities for incorporating digital health solutions into educational settings. However, few are knowledge-based and their potential to help promoting CVH in primary-school children is currently unknown.
SO3 of ICARHE has the ambition to develop a serious game to make CVH health promotion more enjoyable and engaging for children that is safe (i.e. preventing digital addiction), effective and cost-effective, generating sustained benefits, implementable, inclusive (promoting health equity) and scalable for the EU member states. An exploitable strategy for the developed serious game will be put in place in the EU market (SO5).
• To conduct a large-scale European cRCT on CVH in primary school children aged 6 to 8 years
Most randomized controlled interventions in children and adolescents have focused on behavioral outcomes including diet, weight control or physical activity. IThree cRCTs have addressed the benefit of promoting specific items of the CVH score in children. They were school-based cRCTs in pre-school children aged 3 to 5 years in specific areas in Colombia, Spain and socio-economically deprived areas in Harlem, New York City. These interventions consisted of school educational sessions for a full academic year on health knowledge and attitudes including diet, physical activity and body mass index. The feasibility, safety, and effectiveness of these interventions were demonstrated, whereby significant differences between the groups over two years of follow-up post intervention were observed.
SO 2 to 4 of ICARHE have the ambition to test the safety, and effectiveness of a a co-designed intervention to improve the CVH of primary-school children within a cRCT. The added value of this trial is as follows. Firstly, it will be conducted in four diverse European countries, making the intervention a possible scalable solution across Europe. Secondly, it will address a more comprehensive spectrum of CVH additionally considering the biological risk factors (blood pressure, glycemia and total cholesterol) together with sleep health. Thirdly, it will be co-designed with the children and their parents/guardians, teachers, and relevant stakeholders, thereby enabling the trial to be more relevant to the local needs of the target population, a key factor for effectiveness, scalability and sustainability. Fourthly,given increasing evidence on the importance of the social and psychological determinants of health, the extent to which improvement in parents’ health literacy and the children’s well-being contribute to CVH improvement will be explored.
• To provide evidence-based recommendations for primordial prevention implementation in primary-school children across Europe
EU member states have recently released national recommendations for the first 1000 days of life. These are broad recommendations addressing home environment, parent-baby interactions or maternal health during pregnancy. SO 5 of ICARHE has the ambition to provide evidence-based recommendations for the implementation of primordial prevention in primary schools that are scalable across EU member states.

Impact of research: 
Potential delivery of a data educated intervention in schools.
Date proposal received: 
Thursday, 7 September, 2023
Date proposal approved: 
Tuesday, 19 September, 2023
Keywords: 
Epidemiology, Cardiometabolic, Population based data analysis and RCT, Cardiovascular

B4410 - Genome-wide association study and meta-analysis of carotid intima media thickness cIMT - 03/10/2023

B number: 
B4410
Principal applicant name: 
Sonia Anand | McMaster University (Canada)
Co-applicants: 
Amel Lamri
Title of project: 
Genome-wide association study and meta-analysis of carotid intima media thickness (cIMT)
Proposal summary: 

Carotid intima media thickness is a measure of the thickness of wall of the carotid, a blood vessel located near the heart. Throughout the years, fat deposits along these walls (causing atherosclerosis) and the amount of deposits depends on multiple factors including genetic factors, poor diet quality and lack of physical activity. Larger fat deposits (and hence, thicker walls) are associated with a higher risk of cardiovascular disease.
The goals of our study are to
1- identify new genetic markers that predispose to higher levels of fat deposit and thicker carotid walls
2- investigate the age around which these genes are activated (eg. identify which ones are active at an earlier age versus the ones that are activate later in life)

Impact of research: 
Our research will help identify new associated with high cIMT at an early age that could potentially be interesting drug targets. it will also increase our understanding of the development of atherosclerosis and interplay between the genetic predisposition and time/age.
Date proposal received: 
Thursday, 31 August, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), carotid intima media thickness , Statistical methods, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Genome wide association study

B4412 - Reproductive factors and the risk of pregnancy complications a student project linked to B4306 - 18/09/2023

B number: 
B4412
Principal applicant name: 
Fangkun Liu | Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China (China)
Co-applicants: 
Ziwei Teng M.D.
Title of project: 
Reproductive factors and the risk of pregnancy complications: a student project linked to B4306
Proposal summary: 

This is a student project linked to my current project B4306. The reproductive factors including lifestyle, disease status, infection, medication use, nutrient supplements, physical activity, and mental health are associated with pregnancy complications. The adverse outcomes of pregnancy confront the world as a major challenge, with extensive impact on individuals, families, and societies at large. This study will take advantage of the data provided by the Avon Longitudinal Study of Parents and Children to quantify the risk of possible adverse outcomes of pregnancy, and present opportunities to reduce the burden associated with congenital disorders at a population level.

Impact of research: 
Our research may offer more insights into the etiologies of offspring developmental failure on the central nervous system, cognition and intelligence. This may help individuals to choose a more scientific way to avoid maternal exposure to bad factors and get close to good factors, to guarantee a healthy child, or help the governments and medical institutions to establish more appropriate strategies for better maternal and child health care.
Date proposal received: 
Tuesday, 5 September, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Speech/language problem, Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Diabetes, Epilepsy, Infection, Learning difficulty, Mental health, GWAS, Medical imaging, Statistical methods, Birth outcomes, Blood pressure, Environment - enviromental exposure, pollution, Genome wide association study, Intelligence - memory, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, Offspring, Psychology - personality, BMI, Physical - activity, fitness, function, Speech and language, Statistical methods, Cardiovascular, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Development, Equipment - MRI, Endocrine - endocrine disrupters

B4415 - Association of inflammation with cardiac structure in adolescents - 18/09/2023

B number: 
B4415
Principal applicant name: 
Andrew O. Agbaje | University of Eastern Finland (Finland)
Co-applicants: 
Viivi Heijari
Title of project: 
Association of inflammation with cardiac structure in adolescents
Proposal summary: 

Increased left ventricular mass and hypertrophy has been associated with cardiovascular morbidities and mortality in later life. Often employed as surrogate for premature heart damage in the young population, increased left ventricular mass has been associated with risk factors such as elevated blood pressure, arterial stiffness. Recent study in a large cohort of adolescents reported that inflammation may precede early vascular damage in the causal path. It remains unclear whether inflammation associates with left ventricular mass in a large population of community dwelling adolescents who are apparently healthy. This undergraduate thesis will examine the cross-sectional association between inflammation and left ventricular mass/hypertrophy in 17 year old adolescents.

Impact of research: 
The research improves the understanding on the role of inflammation on cardiac structure in youthful life.
Date proposal received: 
Friday, 8 September, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Epidemiology, cardiovascular disease, Medical imaging, Cardiovascular

B4416 - Pathways between neurodevelopmental conditions and Health A longitudinal examination of risk and protective factors - 18/09/2023

B number: 
B4416
Principal applicant name: 
Kirsty Samantha Lee | University of Warwick (United Kingdom)
Co-applicants: 
Ahmad Valikhani, Dr John Galvin, Prof Dieter Wolke , Dr Ayten Bilgin
Title of project: 
Pathways between neurodevelopmental conditions and Health: A longitudinal examination of risk and protective factors
Proposal summary: 

Autism spectrum condition is a lifelong neurodevelopmental condition recognised by its heterogeneous phenotypic manifestations. This heterogeneity not only makes the condition challenging to diagnose but may also lead to misdiagnoses of psychiatric or medical disorders, which can decrease quality of life and wellbeing. Research has shown that psychiatric and medical conditions are highly comorbid with autism, but it is not known if this is due to autism per se (i.e., autism-related genetic mutations and autistic traits) or the effects of environmental risk factors or protective factors. Environmental risk factors (e.g., traumatic experiences, intimate partner violence, bullying, stressful life events) commonly contribute to poor mental and physical health in the general population, but there has been less investigation into their role among autistic individuals. It is also unknown whether protective factors in childhood and adolescence (e.g., positive relationships with parents, school enjoyment, social support) affect the association between autism and psychiatric or medical comorbidities in adolescence and adulthood. In addition to examining these association in the general population who have an autism diagnosis, we will also consider autistic traits (i.e., the broader autism phenotype; BAP) and traits of attention deficit hyperactivity disorder (ADHD), which is highly comorbid in the autistic community. As girls and women were historically neglected in neurodevelopmental research, we will also examine sex differences. The research could have clinical and policy implications for promoting health and wellbeing in the broad autism population, better recognition and earlier diagnosis, especially among girls, and the prevention/promotion of risky/protective environments.

Impact of research: 
The findings may contribute to our understanding of how phenotypic presentations of neurodevelopmental conditions relate to psychiatric, medical and social outcomes This project may identify the underlying mechanisms in the environment that amenable to intervention. Additionally, as the role of sex differences in autism have historically been ignored, our research may inform sex-specific programmes in the provision of healthcare for autistic individuals, including earlier diagnosis. In sum, the findings may have widespread clinical, policy, and research implications.
Date proposal received: 
Wednesday, 13 September, 2023
Date proposal approved: 
Monday, 18 September, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Statistical methods, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Sex differences, Autism, ADHD, Health, Mechanisms

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