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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B4019 - Meta-analysis of Copy Number Variation in Large Consortia - 21/03/2022

B number: 
B4019
Principal applicant name: 
Kimberley Burrows | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Dr Joseph Glessner, Professor Struan Grant, Professor Debbie Lawlor
Title of project: 
Meta-analysis of Copy Number Variation in Large Consortia
Proposal summary: 

[Written by Dr Joseph Glessner]

In the analysis of genetic variation, individual-level data is of great value. Research sites generating such data on human subjects are typically mandated by their institutional review boards (IRBs) not to share this information between institutions and other entities. However, the ability to combine large genetic datasets across research sites is an important tool in understanding the genomic architecture of common complex diseases. Indeed, methods to combine different genome-wide analysis studies (GWAS) of single nucleotide polymorphism (SNP) markers are well established, and they have proved extremely powerful for delving deeper into common diseases such as type 2 diabetes and childhood obesity. However, similar trans-institutional approaches for analyses of copy number variants (CNVs) are relatively in their infancy. Some of the main reasons for this discrepancy include:

1) Non-standard and variable methods to infer CNVs from genotyping data
2) A lack of robust methods for imputation of CNVs across genotyping chipsets
3) The accounting complexities of CNVs across subjects having variable boundaries

This research plan seeks to establish a genome-wide approach to meta-analyze CNVs across sites that comprise the Early Growth Genetic (EGG) Consortium.

Impact of research: 
Improved and refined techniques for novel exploration of the contribution of copy number variation within a consortium setting will greatly improve power to detect associations with common complex disease. This is an underexplored field within consortium settings and may lead to novel insights into the genetic architecture of common complex disease beyond that of SNPs. A successful project will see new/refined methodology that could be used for future projects.
Date proposal received: 
Thursday, 3 March, 2022
Date proposal approved: 
Monday, 21 March, 2022
Keywords: 
Genetics, Obesity, Computer simulations/modelling/algorithms, GWAS, Microarrays, Statistical methods, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Statistical methods

B4024 - Beyond Adverse Childhood Experiences Advancing evidence and methods to understand the health consequences of childhood adversit - 21/03/2022

B number: 
B4024
Principal applicant name: 
Laura Howe | MRC Integrative Epidemiology Unit at the University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
Beyond Adverse Childhood Experiences: Advancing evidence and methods to understand the health consequences of childhood adversit
Proposal summary: 

A rising tide of research and policy interest in Adverse Childhood Experiences (ACEs, e.g. child maltreatment, parental intimate partner violence or substance misuse) has led to substantial financial investment in services to prevent the health consequences of ACEs. These initiatives rest on estimates of the health burden/costs of ACEs. Yet very little research attempts to interrogate the causality of associations between ACEs and health, despite potential confounding by upstream factors such as poverty and genetics. Robust evidence that ACEs causally affect health would strengthen the rationale for investing in interventions that prevent ACEs or seek to mitigate their adverse effects. Yet if some associations are spurious or over-estimates, this risks: costs of ACEs being overstated, scarce public resources being wrongly diverted away from other upstream determinants of health such as poverty, and perpetuating a stigmatising narrative that those exposed to adversity have uniformly poor health.

In BEYOND-ACES, cutting-edge research using prospective longitudinal and genetic data from 6 international cohorts will generate a step-change in evidence about whether ACEs are causally related to health-related behaviours, physical health, and mental health. We will use robust methodologies: difference in difference (DiD) to avoid time-fixed confounding, marginal structural models (MSM) to avoid time-varying confounding, polygenic scores to evaluate gene-environment correlation, and methods to account for genetic confounding. Underpinning this is a cross-cutting programme of methodological innovation: developing DiD and MSM for use with the composite exposures necessary in ACEs research, and evaluating approaches to interrogate whether the health consequences of ACEs differ according to the timing and duration of exposure. BEYOND-ACES will move beyond the current simplistic narrative about ACEs and health, and yield a step change in the quality of research in this field.

Impact of research: 
Interrogating the causality of associations between ACEs and health. Will feed into economic evaluations.
Date proposal received: 
Friday, 11 March, 2022
Date proposal approved: 
Monday, 21 March, 2022
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Obesity, Respiratory - asthma, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity

B4026 - Characterising the relationships between alcohol use and mental health from adolescence to young adulthood a longitudinal study - 21/03/2022

B number: 
B4026
Principal applicant name: 
Hannah Sallis | MRC IEU
Co-applicants: 
Eve Kimber, Professor Marcus Munafo
Title of project: 
Characterising the relationships between alcohol use and mental health from adolescence to young adulthood: a longitudinal study
Proposal summary: 

It has previously been shown that there is a relationship between age of first intoxication (AFI) and mental health disorders. However, many studies in this area tend to focus on the relationship between the AFI and substance-use disorder, rather than other mental illnesses, or how pre-existing mental disorders predict substance-use in teenagers. Burke et al (1990) found that the hazard rate for developing a substance-use disorder is highest when the AFI is between ages 15 and 19 and found that this risk decreases as the individual ages, which is consistent with other literature. This suggests that teenage years are a vulnerable period for individuals as there is a high potential for the development and maintenance of a substance-use disorder. The impact of pre-existing mental health issues on substance use is demonstrated in a study conducted by Sung et al (2004), which found that girls who struggle with anxiety before the age of 16 have an increased risk of substance-use disorder, and boys with a history of depression in childhood and early adolescence also have an increased risk. Research suggested that substance-use disorders can also be a symptom of mental illnesses, for example, Robins et al (1985) found evidence that implies this disorder is a symptom of antisocial personality disorder. However, there is a lack of investigation into whether the AFI is associated with the onset of psychopathological symptoms.

Impact of research: 
This research will help us better understand the long-term relationship between mental health and alcohol use from adolescence to adulthood, which can assist in the development of predictive tools and interventions. For example, this research may help develop a model which can be practically applied to predict development of mental health disorders based off age of first intoxication.
Date proposal received: 
Tuesday, 15 March, 2022
Date proposal approved: 
Monday, 21 March, 2022
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Statistical methods

B4028 - Cord blood and pre-school biomarkers mediating the relationship between maternal obesity and offspring behaviour - 21/03/2022

B number: 
B4028
Principal applicant name: 
Courtney Dow | INSERM UMR1153 (France)
Co-applicants: 
Barbara Heude, Maribel Casas
Title of project: 
Cord blood and pre-school biomarkers mediating the relationship between maternal obesity and offspring behaviour
Proposal summary: 

Maternal obesity is a growing epidemic associated with negative outcomes for both the mother and the infant, including pre-eclampsia, gestational diabetes (GDM), and infants born overweight. Emerging evidence also suggests that pre-pregnancy maternal obesity has a detrimental effect on child neurodevelopment, affecting both cognition and behavioural development. This phenomenon is likely a direct result of a suboptimal environment in the womb. However, obesity is also associated with the activation of the immune system, which may further trigger adverse consequences in the developing fetal brain. A second potential pathway through which maternal obesity may act is through changes in the fetal steroid or hormonal environment. Obese women have increased levels of leptin which have been correlated to higher fetal leptin levels. Leptin is believed to have a role in fetal brain development, specifically behavioural regulation. Though studies have begun examining the role of maternal pre-pregnancy obesity on childhood neurodevelopment, only one study has considered the role of inflammation or hormones as potential biological mechanisms of action. Nevertheless, their role remains unclear.

Impact of research: 
This project will be a valuable contribution into determining a biological mechanism from which maternal obesity can affect child neurodevelopment, both as the first investigation into potential mediators and secondly by using data from multiple cohorts across Europe. These results can provide more evidence into a direct, causal link between maternal obesity and child neurodevelopment.
Date proposal received: 
Wednesday, 16 March, 2022
Date proposal approved: 
Monday, 21 March, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, BMI, Cohort studies - attrition, bias, participant engagement, ethics, Development, Mothers - maternal age, menopause, obstetrics

B4016 - Characterising the relationship between disordered eating behaviours and problematic alcohol use from adolescence to young adult - 21/03/2022

B number: 
B4016
Principal applicant name: 
Hannah Sallis | MRC IEU
Co-applicants: 
Lauren Makin, Professor Marcus Munafo
Title of project: 
Characterising the relationship between disordered eating behaviours and problematic alcohol use from adolescence to young adult
Proposal summary: 

People who exhibit disordered eating behaviours, such as binge eating, restricting, and purging, are at increased risk of problematic alcohol use. It is commonly proposed that this is a partially causal relationship, with behaviours such as binging and restricting actively contributing to the development of problematic alcohol use. This may be because disordered eating behaviours can increase negative affect, reward sensitivity, and impulsivity, which are factors known to contribute to problematic alcohol use.

However, there are also reasons to believe that problematic alcohol use may in turn contribute to the development and maintenance of disordered eating behaviours, through similar mechanisms operating in the opposite direction. Additionally, ‘out of control’ or ‘binge-type’ alcohol use may be particularly distressing for individuals with disordered eating, due to the caloric nature of alcohol, and thus may result in increased compensatory behaviours (i.e., disordered eating behaviours). Longitudinal studies thus far have reported mixed findings regarding the causal direction between disordered eating behaviours and problematic alcohol use and have been hampered either by small sample sizes or poor measures.

Thus, this project aims to investigate and describe the direction(s) of causation between disordered eating behaviours and problematic alcohol use using robust measures and a large sample size.

Furthermore, the literature is unclear on whether purging or bingeing is more related to problematic alcohol use, as many studies have either looked at one or the other, or collapsed them into one category (i.e., ‘bulimic symptoms’). Thus, this study will look to consider the relative magnitude of association of each of these two behaviours, as well as restrictive eating behaviours, and problematic alcohol use.

Impact of research: 
This research will help us better understand the long-term relationship between disordered eating behaviours and alcohol use from adolescence to adulthood, which can assist in the development of predictive tools and interventions.
Date proposal received: 
Wednesday, 9 March, 2022
Date proposal approved: 
Monday, 21 March, 2022
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, Social science

B4027 - Long term impact of the COVID-19 panemic COVID Q 6 - 21/03/2022

B number: 
B4027
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Professor Nic Timpson
Title of project: 
Long term impact of the COVID-19 panemic: COVID Q 6
Proposal summary: 

We have deployed 5 questionnaires to date through the COVID-19 pandemic, together with serology testing and tracked a wide variety of issues around physical and mental health and the impact of the pandemic. We continue our work in the National Core Studies (NCS) consortium to examine the impact of the pandemic across a number of cohort studies (10 in total). This questionnaire will be deployed across these studies.

Impact of research: 
Potential policy relevant findings
Date proposal received: 
Tuesday, 15 March, 2022
Date proposal approved: 
Wednesday, 16 March, 2022
Keywords: 
Epidemiology, Infection

B4020 - ALSPAC EMPHASIS study of childhood height and DNA methylation - 21/03/2022

B number: 
B4020
Principal applicant name: 
Hannah Elliott | University of Bristol (United Kingdom)
Co-applicants: 
Professor Caroline Relton, Dr Matt Silver, Mr Prachand Issarapu, Dr Giriraj Chandak, Professor Caroline Fall
Title of project: 
ALSPAC EMPHASIS study of childhood height and DNA methylation
Proposal summary: 

The aim of this research is to determine the relationship between DNA methylation at the SOCS3 region and both height and mothers social class. Work leading up to this proposal has indicated that SOCS3 methylation may be associated with height and stunting in cohorts based in Lower Middle Income Countries (LMICs). Analysis in ALSPAC will help to answer whether these associations are also present in High Income Countries (HIC) such as the UK. Analysis of genetic data will determine the variance in DNA methylation determined by genetic and/or environment and the causal direction of any associations identified.

Impact of research: 
This project will define the relationship between SOCS3 methylation and SES/child height and allow us to make inferences about the role of SOCS3 in growth and stunting during childhood. Analysis conducted in this project will be published as a peer reviewed journal article.
Date proposal received: 
Friday, 4 March, 2022
Date proposal approved: 
Monday, 14 March, 2022
Keywords: 
Epidemiology, Child Height, Statistical methods, Epigenetic Epidemiology, Epigenetics, Growth, Mendelian randomisation

B4004 - INTIMATE PARTNER VIOLENCE PERPETRATORS THE ORIGINS B3087 - 14/03/2022

B number: 
B4004
Principal applicant name: 
Miguel Perez-Garcia | University of Granada (Spain) (Spain)
Co-applicants: 
Noelia Perez Camara, Miss
Title of project: 
INTIMATE PARTNER VIOLENCE PERPETRATORS: THE ORIGINS B3087
Proposal summary: 

Intimate Partner Violence (IPV) is defined as any violent behavior within an intimate relationship or any other controlling behavior that is conducted by a current or former partner. It is the most common form of violence in women which constitutes a major public health problem worldwide. The current explanatory theories of IPV perpetration can be summarized as feminist/sociocultural, social learning theory-based intergenerational transmission and psychological/psychosocial. According to the feminist/sociocultural theory, domestic violence is a consequence of “patriarchy”. From this view, violence is used as a form of power and control of women by men. The intergenerational transmission theory asserts that domestic violence is based on the exposure to, or observation of, violence in the family of origin. Psychological theories propose that there are psychological, psychiatric, behavioural and neurological risk factors for domestic violence perpetration. In the study of IPV perpetration, it is important to consider the variables addressed by such theories as a whole and from a developmental perspective and there is no study that simultaneously considers all the variables of these explanatory theories. The general aim of our study is to identify those etiological mechanisms linking risk factors for IPV perpetration across development. This study will be the first one that sheds light on which the origins of IPV perpetration are by knowing how IPV perpetration develops. Implications in terms of prevention and treatment will be of a great relevance for public health.

Impact of research: 
Considering the high prevalence and negative consequences of IPV, its prevention is of great importance to public health. Moreover, there is a scarcity of studies that address IPV perpetration from a prospective approach and using large samples. In this line, it is the first study that simultaneously considers all the variables of the current explanatory theories of IPV perpetration (e.g., feminist/sociocultural, social learning theory-based intergenerational transmission and psychological/psychosocial) from a prospective perspective. The further investigation of the current explanatory theories of IPV perpetration using a fully prospective design would benefit in the comprehension of IPV perpetration. Regarding the public health significance of the present research, we expect to identify which variables differentiate IPV perpetrators from those who do not show IPV perpetration. Such investigation will be useful in the treatment and prevention of IPV since we will determine for the first time, the etiological mechanisms involved in IPV perpetration.
Date proposal received: 
Wednesday, 2 March, 2022
Date proposal approved: 
Monday, 14 March, 2022
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Psychology - personality

B3980 - The predictive power of autobiographical memory in shaping mental health of young people - 14/03/2022

B number: 
B3980
Principal applicant name: 
Caitlin Hitchcock | University of Melbourne
Co-applicants: 
Dr Naomi Warne, Ms Dou Hong
Title of project: 
The predictive power of autobiographical memory in shaping mental health of young people
Proposal summary: 

The way in which we remember our past - our autobiographical memory - plays a key role in how we think and feel about ourselves and how we imagine our future. As such, dysfunction within the autobiographical memory system can have a lasting impact on mental health. In this study, we are interested in whether the ability to retrieve specific, detailed memories of the personal past for both positive and negative events can influence whether adolescents develop mental health issues in the future. There is lots of previous research which suggests that having trouble recalling specific memories does predict mental illness in the future, and our study is particularly interested in whether factors such as life stress or family history of mental illness may influence this relationship. We are using meta-analysis to compile datasets from young people all around the world to try and answer this question, and to ensure that our results accurately represent all young people.

Impact of research: 
We hope the clarify the role of an important cognitive system - autobiographical memory - in the first onset of a range of mental health disorders. Further understanding of this prospective relationship will allow us to refine memory-based intervention options for future use as preventative interventions for young people.
Date proposal received: 
Tuesday, 22 February, 2022
Date proposal approved: 
Monday, 14 March, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Cognition - cognitive function

B4007 - Genetic Influences on Sibling Bullying and Mental Health - 09/03/2022

B number: 
B4007
Principal applicant name: 
Umar Toseeb | University of York
Co-applicants: 
Dr John Vincent
Title of project: 
Genetic Influences on Sibling Bullying and Mental Health
Proposal summary: 

Sibling bullying is highly prevalent. Nearly 50% of children are involved in one form or another, with higher rates in some neurodiverse children. Sibling bullying is associated with poor mental health. What remains unclear is if a) sibling bullying leads to poor mental health or whether children with poor mental health are more likely to experience sibling and b) what the rates of sibling bullying are in children with other types of neurodiversity. We will use a genetically sensitive design to address this gap in knowledge.

Impact of research: 
1) to understand the direction of causality in the relationship between sibling bullying and mental health will help to understand what the targets of intervention should be (i.e., mental health or bullying) 2) to understand prevalence of sibling bullying in vulnerable groups will help to shed new light on whether interventions are needed to support these groups, more so than the general population
Date proposal received: 
Thursday, 3 March, 2022
Date proposal approved: 
Wednesday, 9 March, 2022
Keywords: 
Social Science, Learning difficulty, Mental health

B4013 - Asthma Phenotypes and Sputum Biomarkers in High- Medium- and Low-Income Countries - 09/03/2022

B number: 
B4013
Principal applicant name: 
Collin Brooks | Massey University (Research Centre for Hauora and Health) (New Zealand)
Co-applicants: 
Mr Jeroen Burmanje
Title of project: 
Asthma Phenotypes and Sputum Biomarkers in High-, Medium- and Low-Income Countries
Proposal summary: 

Asthma remains a major global public health concern. However, asthma prevalence is different in high-income countries (HICs) and low and middle-income countries (LMICs), and what we know about asthma pathology is generally based on studies in HICs. To address this, the World Asthma Phenotypes Study (WASP) study started in 2016 to better understand types of asthma in five centres around the world; the UK (Bristol: ALSPAC), New Zealand, Brazil, Ecuador, and Uganda. The main objective of this specific project (which is part of WASP) is to focus on the association between soluble airway biomarkers, patterns of airway inflammation, and clinical characteristics, to better understand and characterise types of asthma in the different centres.

Impact of research: 
Date proposal received: 
Wednesday, 23 February, 2022
Date proposal approved: 
Wednesday, 9 March, 2022
Keywords: 
Epidemiology, Respiratory - asthma, Enzyme-Linked Immunosorbent Assay (ELISA) and multiplex bead array assays using the Luminex MAGPIX., Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4015 - Genetic determinants of childhood adversity - 09/03/2022

B number: 
B4015
Principal applicant name: 
Laura Howe | MRC Integrative Epidemiology Unit at the University of Bristol (United Kingdom)
Co-applicants: 
Stephanie Page, Amanda Hughes, Annie Herbert
Title of project: 
Genetic determinants of childhood adversity
Proposal summary: 

Experiencing adversity during childhood, such as maltreatment or family dysfunction, is associated with worse physical and mental health. However, it is possible that associations between childhood adversity and subsequent health are confounded by genetics. Recent studies have demonstrated associations between various polygenic scores and adverse experiences including trauma (1) and bullying (2). Understanding this gene-environment correlation is the first step towards deriving the appropriate confounding adjustments to better estimate the causal impact of childhood adversity on later health.

1 - Peel A et al. Genetic and early environmental predictors of adulthood self-reports of trauma. Br J Psychiatry
. 2022 Feb 2;1-8. doi: 10.1192/bjp.2021.207. Online ahead of print.
2 - Schoeler et al. Multi-Polygenic Score Approach to Identifying Individual Vulnerabilities Associated With the Risk of Exposure to Bullying. JAMA Psychiatry
. 2019 Jul 1;76(7):730-738. doi: 10.1001/jamapsychiatry.2019.0310.

Impact of research: 
Understanding gene-environment correlations that may lead to confounding in studies of the health consequences of adversity
Date proposal received: 
Friday, 25 February, 2022
Date proposal approved: 
Wednesday, 9 March, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Genetic epidemiology, Psychology - personality, Social science

B4018 - Understanding adolescent and early adulthood mental health outcomes of intellectual disability - 14/03/2022

B number: 
B4018
Principal applicant name: 
Paul Madley-Dowd | University of Bristol (United Kingdom)
Co-applicants: 
Dr Dheeraj Rai, Ms Christina Dardani, Dr Laura Hull
Title of project: 
Understanding adolescent and early adulthood mental health outcomes of intellectual disability
Proposal summary: 

Individuals with an intellectual disability (ID) may be more likely to suffer from mental health problems than the general population. We aim to investigate the relationship between ID and mental health using data from a longitudinal study of over 14000 children born in the early 90s with ongoing data collection. We will investigate whether specific risk factors such as cognitive ability, sensory impairments and life events such as bullying may influence this relationship and act as modifiable targets for intervention.

Impact of research: 
Our work will be of relevance to commissioners of health and social care. The results will help in understanding of the mental health care needs of individuals with ID and identification of modifiable targets for intervention will be important for preventing mental health problems in the ID community. The understanding of the mental health needs of individuals with an ID is still limited and despite an increase in policy and research interest in the area, the evidence is extremely limited. Clinical services for adults with an ID are relatively limited in their remit beyond clinical diagnosis in much of the UK and beyond. This work will lead to the conduct of one of the largest and most detailed studies on this topic to date. The evidence produced is likely to contribute to the much needed discussion regarding appropriate service provision and policy in relation to mental health problems in individuals with an ID. Insights into the potential risk or resilience factors may help initiate research into the development and evaluation of interventions to address them.
Date proposal received: 
Tuesday, 1 March, 2022
Date proposal approved: 
Wednesday, 9 March, 2022
Keywords: 
Epidemiology, Learning difficulty, Statistical methods, Cognition - cognitive function

B4000 - General disease factor and developmental risk factors - 01/03/2022

B number: 
B4000
Principal applicant name: 
Yuning Zhang | University of Southampton (United Kingdom)
Co-applicants: 
Sam Cortese, Dr Dennis Golm, Dr Valerie Brandt
Title of project: 
General disease factor and developmental risk factors
Proposal summary: 

More and more evidence suggests a link between mental and physical conditions such as ADHD and obesity (Cortese et al., 2016), eating disorder and inflammatory bowel disease (Larsen et al., 2018). Similar to the g-factor and p-factor (Caspi et al., 2015), Our team at University of Southampton has hypothesised one general disease factor (d-factor; Cortese et a., 2021) that summarises individual’s propensity to both mental and physical disorders, and accounts for the comorbidity between mental and physical conditions. We have been testing this hypothesis using two longitudinal datasets: the millennium cohort study and the 1970 British Cohort Study. We found that from adolescence to adulthood, association between mental and physical conditions strengthen gradually, and that there is indeed a general d-factor that explains individual propensity to develop comorbid mental and physical conditions. We would like to (1) test the hypothesis of d factor longitudinally from childhood to early adulthood, (2) examine the genetic and epi-genetic foundation of the general disease factor, and (3) investigate environmental risk factors related to higher d-factor scores.

Impact of research: 
The outcome of this study will be an important milestone for research into mental and physical health comorbidity.
Date proposal received: 
Monday, 28 February, 2022
Date proposal approved: 
Tuesday, 1 March, 2022
Keywords: 
Pathology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Allergy, Eczema, Epilepsy, Gastrointestinal, Hypertension, Incontinence, Infection, Learning difficulty, Mental health, Obesity, Pain, Bone disorders - arthritis, osteoporosis, Respiratory - asthma, Sexually transmitted diseases, chlamydia, gonorrhoea, Speech/language problem, Developmental disorders - autism, Cancer, Chronic fatigue, Cognitive impairment, Congenital abnormalities, Diabetes, Eating disorders - anorexia, bulimia, Computer simulations/modelling/algorithms, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cardiovascular, Childhood - childcare, childhood adversity, Cognition - cognitive function, Dermatology, Environment - enviromental exposure, pollution, Epigenetics

B4014 - Depression and smoking on the plausibility of the missing not at random assumption using fast causal algorithms - 01/03/2022

B number: 
B4014
Principal applicant name: 
Gareth Griffith | University of Bristol MRC-IEU
Co-applicants: 
Professor Kate Tilling, Dr Ellie Curnow
Title of project: 
Depression and smoking; on the plausibility of the missing not at random assumption using fast causal algorithms
Proposal summary: 

If we want to look at the impact of a given exposure on depression outcomes, we commonly require the assumption that the missingness in our depression indicator is "at random". "At random" is something of a misnomer here, and means "random conditional on measured covariates". In the instance that missingness is in fact not at random, i.e. depression itself affects participants likelihood to respond - then common analytical procedures to investigate the impact of exposures on depression may be biased.

We will develop a method to attempt to address this gap, using the effect of smoking on depression at 18 as a question to demonstrate our proposed approach, which will seek to provide testable conditions under which we can falsify the "missing not at random" assumption.

Impact of research: 
Increase understanding of likely mechanisms driving non-random dropout in cohort studies looking at mental health. Provide a methodological avenue for researchers interested in understanding population predictors of depression.
Date proposal received: 
Thursday, 24 February, 2022
Date proposal approved: 
Tuesday, 1 March, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B4012 - Genome-wide investigation of heritable complex traits in infancy - 09/03/2022

B number: 
B4012
Principal applicant name: 
Angelica Ronald | Birkbeck, University of London (United Kingdom)
Co-applicants: 
Professor Emily Jones, Professor Frank Dudbridge, Dr Alex Havdahl
Title of project: 
Genome-wide investigation of heritable complex traits in infancy
Proposal summary: 

Our recent review of published twin studies revealed that infant behaviour is significantly heritable, with twin heritability estimates ranging between 30 and 80% for psychologically-relevant traits. However, thus far there has been little attempt to study the genetic bases of infant behaviour looking at the DNA.

With this study, we aim to explore the role of common genetic variation on heritable infant behavioural traits. Genome-wide association analyses will be performed for infant psychologically-relevant characteristics collected in the first three years of life in the ALSPAC cohort. Results will then be combined with results from other cohorts in a meta-analysis on a large world-wide sample. Following this gene-discovery phase, we will use state of the art statistical genetic methodology to further investigate genetic influences on infants’ behaviour.

Impact of research: 
This research will advance knowledge on the genetic factors that play a role on infant psychologically-relevant traits, and on the stability and change of such genetic influences across the first years of life. The findings may inform further basic research in genetics, neuroscience and psychiatry.
Date proposal received: 
Wednesday, 23 February, 2022
Date proposal approved: 
Tuesday, 1 March, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, GWAS, Psychology - personality

B3966 - Stratification of ADHD developmental trajectories with evidence from environmental risk factors epi-genetics and neuroimaging - 28/02/2022

B number: 
B3966
Principal applicant name: 
Jianfeng Feng | Fudan University (china)
Co-applicants: 
Dr Tianye Jia
Title of project: 
Stratification of ADHD developmental trajectories with evidence from environmental risk factors, (epi-)genetics and neuroimaging
Proposal summary: 

Individuals with attention deficit hyperactivity disorder (ADHD) may undergo different developmental trajectories throughout adolescence. Previous evidence has indicated that neural signatures and genetics could help to distinguish individuals with persistent ADHD symptoms from those remitted. However, little evidence has been provided to demonstrate whether environmental risk factors, such as substance use, could also affect the development of ADHD symptoms.

Impact of research: 
This study will advance our understanding of the cause between environmental risk factors, (epi-)genetics, and neuroimaging and ADHD, which may reshape future clinical practice. Our study may also help establish a unified approach in understanding the neurobiological mechanism of other neurodevelopmental disorders.
Date proposal received: 
Wednesday, 12 January, 2022
Date proposal approved: 
Monday, 28 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Medical imaging, Equipment - MRI

B4008 - Association between air pollution and cardiovascular health in young adults LongITools - 28/03/2022

B number: 
B4008
Principal applicant name: 
Ana Goncalves Soares | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Prof Nicholas Timpson, Dr Ahmed Elhakeem
Title of project: 
Association between air pollution and cardiovascular health in young adults (LongITools)
Proposal summary: 

This proposal is part of LongITools project (B3289).

A growing body of evidence has shown that exposure to air pollution is associated with higher blood pressure/hypertension, cardiovascular events, and cardiovascular mortality. However, few studies have assessed the impact of air pollution on cardiovascular health in younger individuals.

A meta-analysis of cross-sectional and longitudinal studies has shown that an increase in PM2.5 was associated with higher carotid intima-media thickness (CIMT). Even though there is a growing body of evidence on the association between air pollution and cardiovascular outcomes later in life, very little is known in younger individuals [3]. A study carried out with young adults (mean age 28, SD 1.0) showed that nitrogen dioxide (NO2), but not PM2.5, was associated with increased pulse wave velocity (PWV).

It is also possible that the associations between air pollution and cardiovascular health outcomes differ according to intermediate factors, such as body mass index (BMI). A study with 158 individuals aged 17-22 years found that a 1 standard deviation (SD) change in long-term NO2 exposure was associated with 11.3mg/dL higher total cholesterol and 9.4mg/dL higher low-density lipoprotein cholesterol (LDL-C), and these associations were stronger amongst obese participants, suggesting that obesity might exacerbate the effects of air pollution.

The aim of this study is to assess the long-term associations of air pollution with several measures of cardiovascular health in young adults (i.e. central and peripheral blood pressure, heart rate, PWV and CIMT) and explore possible effect modifications by BMI in these associations.

Impact of research: 
Date proposal received: 
Tuesday, 22 February, 2022
Date proposal approved: 
Monday, 28 February, 2022
Keywords: 
Epidemiology, Cardiovascular disease, Statistical methods, BMI, Cardiovascular, Environment - enviromental exposure, pollution

B4009 - Early-life ambient environmental exposures and blood pressure trajectories LongITools - 28/03/2022

B number: 
B4009
Principal applicant name: 
Ana Goncalves Soares | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Prof Nicholas Timpson, Dr Ahmed Elhakeem
Title of project: 
Early-life ambient environmental exposures and blood pressure trajectories (LongITools)
Proposal summary: 

This proposal is part of LongITools project (B3289).

Blood pressure tracks from childhood to adulthood, and elevated blood pressure in childhood or adolescence is associated with several intermediate markers of cardiovascular disease (CVD) and with CVD events and mortality in adulthood. There is a growing body of evidence showing that ambient environmental exposures, such as air pollution, noise and many characteristics of the built environment are associated with high blood pressure/hypertension in adulthood, and some associations with blood pressure have also been observed in children.

Early-life, especially prenatal and early postnatal, is a period of rapid development and particularly vulnerable to environmental factors, and adverse exposures in this period could lead to long-term health effects, including higher risk of CVD. Some studies have shown associations between prenatal ambient environmental factors and blood pressure in children, including some measures of the built environment (e.g., facility density, facility richness and building density), noise, temperature, and air pollution. Investigating whether early-life ambient environmental factors are also associated with changes in blood pressure in different developmental periods will further contribute to the understanding of the importance of environmental exposures to the risk of hypertension across the life-course.

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we aim to assess the association of a range of ambient environmental exposures in early-life with changes in systolic (SBP) and diastolic blood pressure (DBP) during three developmental periods: childhood, adolescence, and early adulthood. We will also seek to replicate the associations found in ALSPAC in other independent European cohorts part of the LongITools project (Generation R, EDEN, PANIC and NFBC 1986).

Impact of research: 
Date proposal received: 
Tuesday, 22 February, 2022
Date proposal approved: 
Monday, 28 February, 2022
Keywords: 
Epidemiology, Hypertension, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Blood pressure, Cardiovascular, Environment - enviromental exposure, pollution

B4010 - Longitudinal associations of air pollution noise and built environment with glucose and insulin-related traits LongITools - 28/03/2022

B number: 
B4010
Principal applicant name: 
Ana Goncalves Soares | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Prof Nicholas Timpson, Dr Ahmed Elhakeem
Title of project: 
Longitudinal associations of air pollution, noise and built environment with glucose and insulin-related traits (LongITools)
Proposal summary: 

This proposal is part of LongITools project (B3289).

Key modifiable risk factors for hyperglycaemia/diabetes include unhealthy diet, lack of physical activity and overweight/obesity. These are, in part, determined by the built environment, which comprises components such as walkability index, accessibility, population density, land use mix, and food environment. Most of the research assessing the association between built environment and glycaemic traits assesses type 2 diabetes mellitus (T2DM) in adulthood as an endpoint. Very few studies have assessed the association between the built environment and glucose and insulin-related traits in children/adolescents.

The association between air pollution and glucose and insulin-related traits has been more widely studied. Exposures to PM10 and PM2.5 have been associated with higher fasting blood glucose, and several meta-analyses have shown that air pollution is associated with the prevalence and incidence of T2DM. Air pollution, more specifically NO2 and PM10, has also been associated with insulin levels and insulin resistance, and some of these associations have been observed in childhood.

There is also evidence for associations between noise and higher prevalence and incidence of T2DM. To the best of our knowledge, no studies have assessed noise and glucose and insulin-related traits in childhood/adolescence.

This study aims to assess the associations of built environment, air pollution and noise with longitudinal changes in glucose, glycated haemoglobin, insulin and insulin resistance from childhood to early adulthood using data from European prospective studies.

Impact of research: 
Date proposal received: 
Tuesday, 22 February, 2022
Date proposal approved: 
Monday, 28 February, 2022
Keywords: 
Epidemiology, Diabetes, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Cardiovascular, Environment - enviromental exposure, pollution

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