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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B3956 - Investigating the effects on happiness life satisfaction and meaning in life following the transition to parenthood - 27/01/2022

B number: 
B3956
Principal applicant name: 
Claire Haworth | University of Bristol (UK)
Co-applicants: 
Ms. Megan Hamilton, Ms. Nina Di Cara
Title of project: 
Investigating the effects on happiness, life satisfaction, and meaning in life, following the transition to parenthood
Proposal summary: 

The project will investigate the impact that the transition to parenthood has on wellbeing. In particular, the project will focus on understanding how becoming a parent impacts individuals’ happiness, life satisfaction and meaning in life using a longitudinal design.
Research investigating the impact of parenthood on wellbeing produces mixed findings. Some findings indicate that parenthood is associated with detrimental effects on wellbeing (Stanca, 2012), whilst others have suggested that parenthood is associated with improved aspects of wellbeing (Nelson et al., 2013). However, the research investigating the effects of parenthood on wellbeing is difficult to summarise, due to the varying definitions of wellbeing that are used within the literature and the different means of operationalising the term. For example, studies have measured wellbeing by examining symptoms of depression, alcohol abuse, happiness, life satisfaction and frequency of positive and negative emotions. Therefore, this study aims to look at how parenthood effects different aspects of wellbeing individually as there may be differential effects of parenthood on happiness, life satisfaction, and meaning in life. Prior studies have found that parents have higher levels of meaning in life than non-parents (Nelson et al., 2013). However, there are more mixed findings regarding happiness and life satisfaction (Umberson & Gove, 1989). Therefore, the findings regarding the relationship between parenthood and wellbeing do not represent one construct and making concluding statements about parenthood and wellbeing would fail to acknowledge the discrepancies among how wellbeing has been measured and defined.
Previous research has suggested that the relationship between parenthood and wellbeing differs depending on gender, relationship status and financial strain on the parent. It has been reported that mothers experience poorer wellbeing in comparison to fathers (Nelson et al., 2019). Parents who are married may have better wellbeing in comparison to single parents because of the proposed benefits such as division of labour in the home and for parenting tasks (Cunningham & Knoester, 2007). Stanca (2012) also reported that parenthood negatively impacts life satisfaction due to a lack of financial satisfaction and increased financial strain associated with parenthood. Whether the individual is a first-time parent may also be important to investigate because experiences of parenting might not match prior expectations with consequences for mental health in new parents (Harwood et al., 2007).

Impact of research: 
The likely impact of this research is that it could allow a clearer insight into how parenthood impacts happiness, life satisfaction, and meaning in life, as distinct aspects of wellbeing. It is hoped that investigating these as distinct aspects of wellbeing will avoid the problem of making generalised conclusions about parenthood and its effects on wellbeing, which obscures the nuances of this relationship. Instead, the research could indicate whether parenthood effects these outcomes in the same way or in different ways. The consequences of poor mental health among parents and the effects it has on their children have been investigated. It has been proposed that for parents suffering with poor mental health, there is an increased risk of negative impacts to their children’s cognitive, emotional, and behavioural functioning and development (Stein et al., 2014). Therefore, investigating the effects of parenthood on wellbeing outcomes is likely to be important because it could help to identify whether aspects of wellbeing are negatively impacted. This could then be used to inform whether investigation is needed into finding interventions to improve the impacted aspect of wellbeing and could be used to investigate how parental wellbeing influences children.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Thursday, 27 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Parenting, Psychology - personality, Social science

B3955 - Exploring the impact of Autism Spectrum Disorder Traits on symptoms of depression and anxiety during the COVID-19 pandemic - 27/01/2022

B number: 
B3955
Principal applicant name: 
Claire Haworth | University of Bristol (UK)
Co-applicants: 
Ms. Hannah King, Ms. Nina Di Cara
Title of project: 
Exploring the impact of Autism Spectrum Disorder Traits on symptoms of depression and anxiety during the COVID-19 pandemic
Proposal summary: 

The COVID-19 pandemic has severely impacted the lives of people across the world. There is increasing evidence that the mental health of the UK population was significantly worse as a result of the pandemic and restrictions put in place to stop the spread of COVID-19. Further research has identified groups within the population who were more at risk of an increase in symptoms of depression and anxiety. One of these high-risk groups are those with high levels of autistic spectrum traits (ASTs). Indeed, prior to the pandemic, previous studies have found that mental health conditions such as depression and anxiety amongst those with autistic spectrum disorder or ASTs are highly prevalent. However, of the studies investigating the influence of ASTs on mental health conditions during the pandemic published thus far, most have used convenience sampling, clinical samples, small sample sizes or retrospective reporting of mental health prior to the pandemic. Such methods decrease the validity of the findings, and by using only clinical samples (i.e. only including people who have a clinical diagnosis of autistic spectrum disorder), those who are not able to get a clinical diagnosis due to factors such as socioeconomic status are not represented in the sample, further reducing validity. Therefore, this study will not be using clinical diagnostic data, and instead will use data from a continuous measure of ASTs collected within ALSPAC. Research using birth cohorts such as ALSPAC allow for a comparison of symptoms of depression and anxiety before and after the pandemic, which can help establish whether changes in these symptoms coincide with the pandemic. Furthermore, due to the longitudinal nature of ALSPAC, potential confounding factors such as gender can be adjusted for. This current project will be investigating the influence of Autistic Spectrum Traits (ASTs) on symptoms of depression and anxiety experienced as a result of the COVID-19 pandemic within the ALSPAC population. Further to this, previous literature has highlighted the importance of social interaction and communication when considering the factors related to mental health concerns amongst those with ASTs. Specifically, adults with ASTs who report feelings of loneliness and lack of social contact also tend to report increased symptoms of anxiety and depression. In the context of this pandemic, this factor is highly relevant due to social distancing and self-isolation rules. Therefore, the second part of this study will aim to investigate whether the association between autistic spectrum traits and anxiety and depression depended on changes in social contact as a result of restriction arising from the COVID-19 pandemic.

Impact of research: 
Through exploring how varying autistic traits have influenced changes in symptoms of depression and anxiety since the pandemic began, findings could contribute to the understanding of more vulnerable groups with regard to mental health during the pandemic. Consequently, this could facilitate an improvement in mental health support amongst those with autistic traits. Further to this, by exploring the impact that social contact has had on depression and anxiety symptoms, a deeper understanding of the factors worsening mental health amongst those with autistic traits can be achieved. This could subsequently help prevent further deterioration in mental health.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Thursday, 27 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B3954 - Understanding the Relationship Between Gratitude and Meaning in Life in the ALSPAC Cohort Study - 27/01/2022

B number: 
B3954
Principal applicant name: 
Claire Haworth | University of Bristol (Uk)
Co-applicants: 
Ms. Amy Griffin, Ms Nina Di Cara
Title of project: 
Understanding the Relationship Between Gratitude and Meaning in Life in the ALSPAC Cohort Study
Proposal summary: 

This project will investigate the relationship between gratitude and meaning in life. There is a large body of evidence demonstrating a positive association between gratitude and wellbeing (Sansone & Sansone, 2010; Wood et al., 2010). However, research into the relationship between gratitude and specific aspects of wellbeing, namely eudaimonic wellbeing, is lacking. Eudaimonic wellbeing refers to the extent to which someone is fully functioning, focusing on meaning and self-realisation (Ryan & Deci, 2001). Meaning in life is a key indicator of eudaimonic wellbeing, therefore by investigating the predictive relationship between gratitude and meaning in life, this study will enable insights into the relationship between gratitude and eudaimonic wellbeing. In addition, this study aims to investigate whether the relationship between gratitude and meaning in life is stronger in some individuals than others, such that this study will investigate the moderating role of gender, qualification, and childhood socioeconomic status. The potential moderating role of these variables will be investigated because there is evidence suggesting that gender moderates the willingness to express gratitude, with men being less likely to feel and express gratitude than women (Kashdan et al., 2009). Additionally, there is evidence that measures of childhood socioeconomic status are associated with wellbeing, with more disadvantaged childhood socioeconomic status being associated with worse mental wellbeing at middle-age (Wood et al., 2021). Finally, there is mixed evidence regarding the relationship between educational attainment and wellbeing (Nikolaev, 2018). Time permitting, this study will also explore how the relationship between gratitude and eudaimonic wellbeing differs to the relationship between gratitude and hedonic wellbeing. Hedonic wellbeing focuses on pleasure and happiness (Ryan & Deci, 2001), and will be measured by subjective happiness and life satisfaction. Overall, this study will provide implications for gratitude interventions, which are increasingly being advocated to improve wellbeing (Rash et al., 2011). This research will enable conclusions to be made regarding who is likely to receive the optimum benefit from gratitude interventions, based on the findings of the moderation analysis.

Impact of research: 
It is hoped that this research will inform our understanding about the relationship between gratitude and eudaimonic wellbeing, including who this relationship is strongest for. This will enable inferences to be made regarding the utility of gratitude interventions. Gratitude interventions are positive psychology interventions and have been shown to be effective in improving wellbeing (Kardas et al., 2019). However, it is reasonable to assume that if the relationship between gratitude and meaning in life is stronger in some individuals, the efficacy of gratitude interventions may also be greater for these individuals. Therefore, by establishing the moderators of the relationship between gratitude and meaning in life, this study will have important implications regarding the utility of gratitude interventions, for example who could benefit from them the most. Additionally, this study will provide important insights into the relationship between these different measures of wellbeing. Despite the literature indicating that gratitude is an important variable with regards to wellbeing (Sansone & Sansone, 2010), there is little known about whether this extends to eudaimonic as well as hedonic wellbeing. Seligman (2012) placed emphasis on the importance of investigating eudaimonic wellbeing as he argued it is the most long-lasting form of wellbeing, hence an important target for intervention. Therefore, understanding the relationship between gratitude and eudaimonic wellbeing can have great impact in this field.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Thursday, 27 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality, Social science

B3953 - The Effects of Parenthood on Feelings of Competence Autonomy and Relatedness - 27/01/2022

B number: 
B3953
Principal applicant name: 
Claire Haworth | University of Bristol (UK)
Co-applicants: 
Ms. Beatrice Knights, Ms. Nina Di Cara
Title of project: 
The Effects of Parenthood on Feelings of Competence, Autonomy and Relatedness
Proposal summary: 

Self-determination theory states that humans have three Basic Psychological Needs: competence, autonomy and relatedness. These needs are associated with motivation and self-regulation. When the needs are satisfied humans experience optimum well-being, so psychological need satisfaction is very important. This project will examine how parenthood effects competence, autonomy and relatedness. Becoming a parent is a life changing event and causes many changes to lifestyle and well-being so this project will investigate how the Basic Psychological Needs are affected by parenthood. There is limited previous literature which investigates this. Additionally, it will be explored how the effect is different for mothers and fathers. Several other exploratory questions will be assessed to investigate how the effect of parenthood on the Basic Psychological Needs is linked to other variables such as well-being, education level and relationship status.

Impact of research: 
There is not much previous research on the specific effect becoming a parent has on the Basic Psychological Needs. This research will hopefully provide a robust answer to how competence, relatedness and autonomy are affected by parenthood. This is highly relevant in the real world as it can show how to best support parents, especially new parents who are perhaps struggling. This in turn would have benefits for not only parents but their children too.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Thursday, 27 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Wellbeing, Statistical methods, Parenting, Social science

B3979 - Proposal Trauma mental health and educational outcomes - 24/01/2022

B number: 
B3979
Principal applicant name: 
Sarah Halligan | University of Bath (UK)
Co-applicants: 
Layla Rashid
Title of project: 
Proposal Trauma, mental health and educational outcomes
Proposal summary: 

Using existing dataset B3837
Children exposed to trauma during their early childhood are at a higher risk of early onset of mental disorders. Bereavement is one of the most prevalent adversities that children face. Empirical literature has highlighted child bereavement to be associated with lower emotional, behavioural, and social wellbeing during adolescence. Early to mid-adolescence is a critical developmental period for the onset and maintenance of psychopathology. A combination of personal attributes, family circumstances, and the nature of supportive networks outside the immediate family are found to be crucial for resilience when faced with early life trauma such as loss. Yet, little research has examined protective factors for children that have experienced bereavement and of those that have, there is limited understanding of the role of amenable maternal factors in improving mental health outcomes. Identifying modifiable maternal factors that may contribute to the development of resilience in children who have been exposed to childhood loss provides opportunity for early intervention. Therefore, the current study aims to examine whether modifiable maternal factors mediate the relationship between child bereavement and internalising or externalising problems during adolescence and early adulthood.

Impact of research: 
The current study could identify whether maternal mental health and parental practices moderate the relationship between child bereavement and internalising and externalising symptoms. Identifying modifiable maternal factors that may contribute to the development of resilience in children who have been exposed to childhood trauma provides opportunity for early intervention.
Date proposal received: 
Sunday, 23 January, 2022
Date proposal approved: 
Monday, 24 January, 2022
Keywords: 
Social Science, Mental health, Statistical methods, Childhood - childcare, childhood adversity

B3943 - Disease risk prioritisation in early life using polygenic risk profiles - 24/01/2022

B number: 
B3943
Principal applicant name: 
Tom Richardson | MRC Integrative Epidemiology Unit (IEU) (United Kingdom)
Co-applicants: 
Ms Si Fang, Prof George Davey Smith, Professor Tom Gaunt
Title of project: 
Disease risk prioritisation in early life using polygenic risk profiles
Proposal summary: 

Polygenic risk score (PRS) have the potential to stratify individuals at high risk of disease. Using a PRS in conjunctioon with traditional risk factors has been shown to enhance the risk prediction of disease outcomes in multiple studies. Exploiting genetic variants associated with disease risk from multiple genome-wide association studies for different risk factors and disease have been reported to outperform single-disease PRS. We hypothesis that with the inclusion of genetic variants associated with modifiable risk factors and biomarkers for disease onset and progression, PRS may provide enhanced risk stratification before the presence of risk factors and enable disease prevention in early life.

In this study, we will develop both single and multi-trait PRS models for complex traits in the UK Biobank and validate their performance in terms of prediction and stratification over the life course using data from participants in the ALSPAC cohort study.

Impact of research: 
We hope to be able to demonstrate that using human genetics can be a powerful approach to prioritising individuals at elevated disease risk during early stages in the lifecourse. This will allow a long window of opportunity for disease prevention.
Date proposal received: 
Friday, 21 January, 2022
Date proposal approved: 
Monday, 24 January, 2022
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Allergy, Eating disorders - anorexia, bulimia, Eczema, Epilepsy, Fertility/infertility, Gastrointestinal, Hypertension, Incontinence, Infection, Learning difficulty, Mental health, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, Pain, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Respiratory - asthma, Sexually transmitted diseases, chlamydia, gonorrhoea, Speech/language problem, Bone disorders - arthritis, osteoporosis, Developmental disorders - autism, Cancer, Chronic fatigue, Cognitive impairment, Congenital abnormalities, Diabetes, GWAS, Metabolomics, NMR, Proteomics, RNA, Statistical methods, Genetic epidemiology, Genome wide association study, Mendelian randomisation, Statistical methods

B3975 - Consequences of adolescent depression - 24/01/2022

B number: 
B3975
Principal applicant name: 
Alex Kwong | Bristol/Edinburgh
Co-applicants: 
Mr Kevin Carr, Ms Tariro Chatiza, Professor Andrew McIntosh, Dr Heather Whalley
Title of project: 
Consequences of adolescent depression
Proposal summary: 

Depression is a complex and multifaceted disease, that will commonly onset during adolescence. Those who experience an episode during adolescence are much more likely to experience future episodes throughout adolescence and later adulthood. Equally, they are much more likely to experience deficits in educational attainment, social functioning, along with a greater likelihood of poorer physical and mental health (including co-morbidities with other psychiatric traits and substance misuse). The overarching aim of this project is to quantify the burden of adolescent depression using the prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC). As a society, it is important to establish any links between depressive symptoms in childhood/adolescence and later deficits in early adulthood in order to inform public policies. This will help identify those who are at higher risk of encountering particular physical, psychosocial or economic problems in early adulthood and to ensure the necessary resources are in place for support.

Impact of research: 
Hopefully showing impact of adolescent depression
Date proposal received: 
Monday, 17 January, 2022
Date proposal approved: 
Monday, 24 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B3971 - The combined role of physical activity and dietary factors for musculoskeletal health during growth - 24/01/2022

B number: 
B3971
Principal applicant name: 
Dimitrios Vlachopoulos | University of Exeter (United Kingdom)
Co-applicants: 
Ms Rong Huang, Ms Annie Constable, Dr Alan Barker, Dr Luis Gracia-Marco , Maria Papageorgiou, Prof Krasimira Tsaneva-Atanasova , Dr Karen M. Knapp
Title of project: 
The combined role of physical activity and dietary factors for musculoskeletal health during growth
Proposal summary: 

Osteoporosis increases the risk of fracture due to decreased bone mass and deterioration of its structure which causes bone fragility. Low peak bone mass (PBM) at the end of adolescence or at the early stage of adulthood is a risk factor of osteoporosis. Bone development during growth is crucial for bone health throughout the whole life. Although the variation in bone outcomes is determined by heredity, lifestyle-related factors including physical activity (PA) and dietary habits can explain up to approximately 30% of the variation in PBM. It is known that sufficient moderate-to-vigorous PA levels and sufficient nutritional intakes, such as calcium, protein and vitamin D are needed to promote bone development. However, only a few studies focused on the combined and interactive effects between the dietary intakes and PA on bone health during growth. In addition, body mass is an important predictor of bone mineral content, according to previous studies, lean mass has a positive association with bone development, while the role of fat mass to bone is still controversial. Previous paediatric studies indicate the partial influence of endocrine markers on bone growth and especially during puberty, but the mediating role of endocrine markers on the relationship between body composition and PA with bone growth requires further research. Therefore, the overall objective of this research project is to assess the combined role of physical activity and dietary factors with bone development and examine the role of endocrine markers and body composition from childhood to early adulthood.

Impact of research: 
It is hoped to provide novel evidence about the balance of body composition components for bone health and the combined role of physical activity and diet for bone development from childhood to early adulthood. These results may bring a new perspective to public bone health improving recommendations.
Date proposal received: 
Monday, 17 January, 2022
Date proposal approved: 
Monday, 24 January, 2022
Keywords: 
Epidemiology, Bone disorders - arthritis, osteoporosis, Medical imaging, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Nutrition - breast feeding, diet, Physical - activity, fitness, function, Puberty

B3973 - Maternal vitamin D status during pregnancy and the risk of congenital heart disease in the offspring - 17/03/2022

B number: 
B3973
Principal applicant name: 
Deborah A Lawlor | University of Bristol
Co-applicants: 
Mr. Kurt Taylor, Ms Karen Christina Walker
Title of project: 
Maternal vitamin D status during pregnancy and the risk of congenital heart disease in the offspring
Proposal summary: 

Congenital heart disease (CHD) is a group of diseases with defects in the heart that occur during fetal life when the heart is formed. CHD occurs in 1% of births each year with causes not fully known. Most cases are believed to be caused by effects of both genes and risk factors that could be changed to prevent CHD (1,2). We are interested in identifying these modifiable risk factors. Several risk factors have been suggested including maternal diet intake (3). We would like to investigate the possible association between maternal vitamin D status and the risk of CHD in the child. A study from 2018 found that low maternal vitamin D was associated with a higher risk of CHD in the offspring (2). That study used blood markers of vitamin D measured approx. 15-months after birth as a proxy for mother’s vitamin D in early pregnancy. Because of the strong effects of sunlight and season on vitamin D levels the measures might not be a good indicator of the mother’s vitamin D in early pregnancy. We would like to use ALSPAC data to investigate the association of mother’s blood vitamin D in early pregnancy on their child’s risk of CHD. ALSPAC is an ideal study to improving our understanding of whether ensuring pregnant women have sufficient vitamin D could prevent CHD. It has measures of blood vitamin D (4), details of all cases of CHD including those that were diagnosed after birth (5), and information on factors that could confound the results.

Impact of research: 
Knowledge from the present study will contribute with valuable insights into risk factors for congenital heart disease.
Date proposal received: 
Friday, 14 January, 2022
Date proposal approved: 
Monday, 17 January, 2022
Keywords: 
Epidemiology, Congenital abnormalities, Statistical methods, Mendelian randomisation

B3967 - Epigenetics of changing traits - 17/01/2022

B number: 
B3967
Principal applicant name: 
Andrew Simpkin | NUI, Galway (Ireland)
Co-applicants: 
Anna Grossbach
Title of project: 
Epigenetics of changing traits
Proposal summary: 

The last decade has seen a dramatic improvement in our understanding of how our genes affect our height, body mass index (BMI), mental health, cancer risk, and many other traits. This has been facilitated by technological developments which allow us to measure a persons’ epigenetic data accurately and economically. Almost all epigenetic studies investigate traits collected at a single timepoint (e.g. adult height), and the epigenetic sites associated with these traits are then found using an epigenome-wide association study (EWAS). However, some traits such as BMI change over time, and the epigenetics of these repeatedly measured traits remain poorly understood. This project will apply new approaches for epigenetic analysis of longitudinal traits - in particular BMI measured repeatedly from birth to adulthood and depressive symptoms from later childhood through adolescence.

Impact of research: 
This research has major potential. The epigenetic analysis of changing/longitudinal phenotypes has yet to be developed, while methods are available in the GWAS context. Therefore, strong results in this study could lead to discoveries across a range of changing phenotypes, as longitudinal and epigenetic data continue to be collected more regularly. With ALSPAC/ARIES a leading cohort for epigenetic data analysis, these developments will open lots of pathways for research using data from Bristol.
Date proposal received: 
Thursday, 13 January, 2022
Date proposal approved: 
Monday, 17 January, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Obesity, Statistical methods, Development, Epigenetics, Growth, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3972 - The relationship between the timing of prenatal alcohol exposure DNA methylation and depressive symptom trajectories - 17/01/2022

B number: 
B3972
Principal applicant name: 
Alexandre Lussier | Massachusetts General Hospital (United States)
Co-applicants: 
Dr. Erin C. Dunn
Title of project: 
The relationship between the timing of prenatal alcohol exposure, DNA methylation, and depressive symptom trajectories
Proposal summary: 

Prenatal alcohol exposure (PAE) is a potent risk factor for depression, with several studies showing that moderate levels of PAE can more than double depression risk. However, the biological mechanisms linking alcohol exposure to long-term vulnerability for depression remain poorly understood. One possibility is that PAE reprograms the epigenome through DNA methylation (DNAm), epigenetic modifications that do not change the sequence of the genome, but can alter gene expression. Both animal and human studies suggest that PAE can induce lasting DNAm changes in the brain and periphery, including in blood and buccal epithelial cells, and that these DNAm profiles are associated with disease risk. Despite these known links between PAE, DNAm, and depression, there are three main gaps in the literature.

First, most human epigenetic studies are cross-sectional and cannot evaluate the causal links between PAE, epigenome-wide DNAm, and depression. As such, it remains unknown whether the relationship between PAE and depression is causal, requiring additional genetic and environmental analyses to parse this relationship.

Second, nearly all studies define PAE as any exposure to alcohol between conception and birth, despite recent evidence that the effects of early-life exposures may have vary depending on when they occur. As such, it remains unknown whether there are specific trimesters or sensitive periods when children are more vulnerable, PAE differentially affects DNAm patterns, and prevention efforts might be most effective.

Third, depression can manifest through different time-dependent patterns after its initial onset, varying with regards to symptom levels, recurrence, and length. Given that a single timepoint cannot fully capture this time-dependent variability, we recently harnessed repeated measures of depressive symptoms to characterize a set of unique depressive symptom trajectories across childhood and adolescence (Lussier 2020; Hawrilenko 2020). However, it remains unclear when and how prenatal risk factors, such as alcohol, influence the manifestation of depressive symptoms across development.

As such, we seek to extend our prior work, which focused on sensitive periods for childhood adversity, to further investigate the relationship between prenatal alcohol exposure, DNAm, and depressive symptom trajectories across development. The central hypothesis we will test is that PAE has causal and time-dependent influences on depression heterogeneity across development, with measurable effects on depressive symptom trajectories and epigenetic processes from age 4 to 24.

Impact of research: 
Previous reports estimate that 10-15% of children are exposed to alcohol during pregnancy; numbers that are expected to rise due to the increases in alcohol use during the ongoing COVID-19 pandemic. By identifying the causal link between PAE and depression, this research will highlight the importance of PAE as a key modifiable and targetable factor in the prevention of depression. Through this work, we will also identify the molecular mechanisms that drive risk for depression across development and determine the optimal trimesters when interventions can be implemented to reduce the impact of prenatal alcohol exposure on depression risk. Specifically, we will identify a set of epigenetic biomarkers influenced by prenatal alcohol exposure and that predict the manifestation of depressive symptoms across development, as well as determine the trimesters when alcohol is most likely to causally affect these DNAm marks. Ultimately, this work will identify the specific periods when PAE can influence depression, which will help target interventions to the individuals who are at higher risk for early-onset depression.
Date proposal received: 
Thursday, 13 January, 2022
Date proposal approved: 
Monday, 17 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Environment - enviromental exposure, pollution, Epigenetics, Genetic epidemiology, Genetics, Mendelian randomisation, Nutrition - breast feeding, diet, Parenting

B3969 - Contributions of fat and lean mass to blood pressure phenotypes in the young - 17/01/2022

B number: 
B3969
Principal applicant name: 
Scott Chiesa | UCL (United Kingdom)
Co-applicants: 
Valerie Mok
Title of project: 
Contributions of fat and lean mass to blood pressure phenotypes in the young
Proposal summary: 

Using a recall-by-genotype design, we have recently shown increases in BMI to be causally related to elevations in systolic - and to a lesser extent - diastolic blood pressure. While these changes are often attributed to the effects of excess adiposity, increases in BMI are known to arise from increases in both fat and underlying lean tissue, both of which may drive changes in blood pressure. This student project aims to investigate the extent to which these differing tissue types may contribute to changes in blood pressure commonly observed in the young.

Impact of research: 
Conferences presentations and combination with other analyses to generate paper in high-impact journal.
Date proposal received: 
Thursday, 6 January, 2022
Date proposal approved: 
Monday, 17 January, 2022
Keywords: 
Epidemiology, Hypertension, Obesity, population study, Blood pressure, BMI, Cardiovascular

B3968 - Contributions of fat and lean mass to structural vascular adaptations in the young - 17/01/2022

B number: 
B3968
Principal applicant name: 
Scott Chiesa | UCL (UK)
Co-applicants: 
Priyanka Iyer
Title of project: 
Contributions of fat and lean mass to structural vascular adaptations in the young
Proposal summary: 

In the absence of hard CVD endpoints in the young, early structural changes within the heart and arteries - such as an increase in left ventricular mass or a thickening or stiffening of the major arteries - are often used in early prevention research as surrogate measures of early disease. Many studies have related changes in these phenotypes at a young age to increases in either BMI or body fat %, suggesting that excess adiposity at an early age may drive pathophysiological changes within the heart and vessels. Both of these are crude measures of adiposity, however, with the former unable to separate fat from lean mass, and the latter unable to quantify absolute levels of each tissue type. The extent to which these phenotypic changes are driven by fat mass per se rather than a combination of fat and lean mass remains equivocal.

Impact of research: 
Conferences presentations and combination with other analyses to generate paper in high-impact journal.
Date proposal received: 
Thursday, 6 January, 2022
Date proposal approved: 
Monday, 17 January, 2022
Keywords: 
Epidemiology, Obesity, population study, Cardiovascular

B3949 - Assessing the hidden gateways into gambling and policies to reduce problem gambling - 10/01/2022

B number: 
B3949
Principal applicant name: 
Jonathan Cave | Supervisor (or University of Warwick) (United Kingdom)
Co-applicants: 
Ben Ho
Title of project: 
Assessing the hidden gateways into gambling and policies to reduce problem gambling
Proposal summary: 

This research paper will look at the gateways into gambling and in particular, problem gambling. Through a quantitative and statistical approach, we hope to identify the behavioural characteristics that may be associated with problem gamblers. Once identified, potential policies will be suggested to dissolve the issue of problem gambling.

Impact of research: 
Contribution to understanding of correlates and causal patterns behind problem gambling (also as a model for other 'addicitive' behaviours with societal reinforcers).
Date proposal received: 
Wednesday, 5 January, 2022
Date proposal approved: 
Monday, 10 January, 2022
Keywords: 
Economics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Intelligence - memory, Social science, Statistical methods

B3965 - Can heavy menstrual bleeding be used to improve the prediction and prevention of cardiovascular disease in women - 05/01/2022

B number: 
B3965
Principal applicant name: 
Gemma Sharp | MRC IEU
Co-applicants: 
Title of project: 
Can heavy menstrual bleeding be used to improve the prediction and prevention of cardiovascular disease in women?
Proposal summary: 

Cardiovascular disease (CVD, e.g. heart attack, stroke) is the leading cause of death in women. Yet women with CVD remain understudied, under-recognised, underdiagnosed and undertreated. Therefore, women have not experienced the same decline in CV rates that has occurred in men in recent decades.
General practitioners currently use CVD risk prediction tools that use traditional risk factors such as blood pressure and cholesterol. We propose that a CVD risk assessment tool which incorporates menstrual data could improve the prediction/prevention of CVD in women.
Recent research suggests that menstrual symptoms such as heavy periods may predict future CVD. Examination of our local electronic health records revealed that women having surgery for heavy menstrual bleeding (HMB) had a seven times greater risk of death from a heart attack than the general female population. Women undergoing hysterectomy for benign causes (e.g. HMB) also had increased CVD, even if the ovaries were not removed.(2).
There are many underlying causes of HMB. These may be non-structural (normal womb at scan) or structural (fibroids/adenomyosis) causes and may be influenced by genetics. However, the relationship between the symptom of HMB, its underlying cause and CVD risk has not been systematically evaluated.
This project will evaluate: (1) if there is an association between the symptom or underlying cause of HMB and future CVD by examining anonymised electronic health records and longitudinal population-based cohort studies of women across the life-course. This will determine if menstrual data would be useful in the prediction of future CVD. (2) if inclusion of relevant menstrual data (informed by our population data studies) and/or other female-specific risk factors (from published literature) in current CV risk prediction tools improves their prediction of CVD. We will use two independent population studies from the UK and Australia to validate our findings. (3) if adoption of a CV risk prediction tool that incorporates female-specific risk factors is feasible in clinical practice to improve the prevention of CVD. We will ask three general practices to use the new female-specific tool on pre-menopausal women. We will assess the number of women it is used in, how user friendly the tool is and also examine the anonymised electronic health records of those it is used in to determine the rate of prescription of CV preventative medicines (e.g. blood pressure medications, statins). These results will inform the design of a future, larger trial to assess the effectiveness of this new tool versus the currently used tools.
This project combines the expertise of gynaecologists, cardiologists and epidemiologists to analyse data from populations to inform clinical practice. We aim to inform the inclusion of relevant menstrual data in CVD risk assessment tools and inform future studies to evaluate their performance in the identification of pre-menopausal women at risk of CVD, allowing early implementation of effective preventative strategies to reduce CV disease and death in women.

Impact of research: 
Date proposal received: 
Thursday, 30 December, 2021
Date proposal approved: 
Wednesday, 5 January, 2022
Keywords: 
Epidemiology

B3964 - High neighbourhood-level deprivation collective efficacy and conduct disorder behaviours A network analysis - 23/12/2021

B number: 
B3964
Principal applicant name: 
Ted Barker | King's College London (United Kingdom)
Co-applicants: 
Yi An Liao
Title of project: 
High neighbourhood-level deprivation, collective efficacy and conduct disorder behaviours: A network analysis
Proposal summary: 

High neighbourhood-level deprivation and low levels of neighbourhood collective efficacy (social cohesion and informal social control) are believed to work together to increase the development of conduct disorder (CD) behaviours, such as lying, fighting, stealing. However, in practice, neighbourhood deprivation has typically not been examined longitudinally and deprivation has often been solely based on neighbourhood-level socioeconomic status rather than a wide range of objective census-level indicators. In addition, CD behaviours have typically been examined using a summed score of behaviours, rather than assessing what particular CD behaviours (e.g., physical aggression) interact with low levels of social cohesion, informal social control and associated risks (e.g., affiliating with deviant peers) under varying levels of longitudinal deprivation exposures.

Impact of research: 
A peer reviewed publication at a decent impact factor (IF > 6.0)
Date proposal received: 
Thursday, 23 December, 2021
Date proposal approved: 
Thursday, 23 December, 2021
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Childhood - childcare, childhood adversity

B3963 - Timing of adolescent growth and maturation and related in utero stressors - 05/01/2022

B number: 
B3963
Principal applicant name: 
Ahmed Elhakeem | MRC IEU
Co-applicants: 
Title of project: 
Timing of adolescent growth and maturation and related in utero stressors
Proposal summary: 

The aim of this paper is to leverage repeated measurements from the ALSPAC birth cohort to describe the timing, chronological sequence, and interrelationships between the maturational processes and events of puberty, and to investigate the associations of key prenatal stressors with these derived indicators of puberty timing (i.e., with all early to late signs of puberty).

Impact of research: 
This work will be of interest to researchers, clinicians, policymakers, and the wider public
Date proposal received: 
Wednesday, 22 December, 2021
Date proposal approved: 
Wednesday, 22 December, 2021
Keywords: 
Endocrinology, Statistical methods, Development

B3961 - Integrating genetics epigenetics and metabolomics to identify early life origins of adult disease - 05/02/2022

B number: 
B3961
Principal applicant name: 
Joel Hirschhorn | Boston Children's Hospital/Broad Institute of MIT and Harvard (United States)
Co-applicants: 
Dr. Mary Elizabeth Patti, Dr. Anders Eliasen
Title of project: 
Integrating genetics, epigenetics and metabolomics to identify early life origins of adult disease
Proposal summary: 

We will use multiple types of data from children in ALSPAC and other childhood cohorts to ask what factors, already evident in children, are causal precursors of future disease. We will focus on molecules that circulate in the blood (metabolites), factors inherited in the genome (genetic variants), and special modifications of the genome (epigenetics, methylation). By combining data from children for genetic variants, epigenetics and metabolites, we can ask whether there are particular metabolites or epigenetic factors that are causal precursors of diseases like obesity, coronary artery disease (CAD), and type 2 diabetes (T2D). Understanding the early causal factors of future disease could guide earlier and therefore potentially more effective interventions.

Impact of research: 
We hope to identify metabolic and/or epigenetic childhood markers that are associated with genetic risk of future cardiometabolic disease and to assess them for evidence of causality using Mendelian randomization. If successful, these biomarkers may be part of early screening to guide intervention, and if causal may give rise to new therapeutic hypotheses that are based in causal mechanisms.
Date proposal received: 
Tuesday, 21 December, 2021
Date proposal approved: 
Tuesday, 21 December, 2021
Keywords: 
Genetics, Diabetes, Obesity, coronary artery disease hyperlipidemia central adiposity nonalcoholic fatty liver disease metabolic syndrome hypertension, GWAS, Metabolomics, Statistical methods, Methylation (epigenetics), Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Mendelian randomisation, Metabolic - metabolism, Nutrition - breast feeding, diet, Statistical methods, Blood pressure, BMI, Cardiovascular, Epigenetics, Genetic epidemiology, Genetics, Genomics, Genome wide association study

B3944 - Ribosomal DNA copy number influences birth weight - 21/12/2021

B number: 
B3944
Principal applicant name: 
Vardhman Rakyan | Queen Mary University of London
Co-applicants: 
Dr Fran Rodriguez-Algarra
Title of project: 
Ribosomal DNA copy number influences birth weight
Proposal summary: 

Ribosomal DNA is a part of our DNA that is present as many copies (most genes are only present as two copies). Because of this reason, the rDNA is typically ignored in large scale genetic studies. We believe that the number of copies of rDNA influences a babies birth weight.

Impact of research: 
An improved understanding of the genetic basis of birth weight variation.
Date proposal received: 
Monday, 20 December, 2021
Date proposal approved: 
Tuesday, 21 December, 2021
Keywords: 
Genetics, Birth weight, DNA sequencing, Birth outcomes, BMI, Genetics, Whole genome sequencing

B3959 - Rethinking mental health difficulties - 20/12/2021

B number: 
B3959
Principal applicant name: 
Jenny Retzler | University of Huddersfield
Co-applicants: 
Dr Chris Retzler
Title of project: 
Rethinking mental health difficulties
Proposal summary: 

The symptoms experienced by young people with mental health difficulties rarely fit neatly into one diagnosis. For more than half of young people with difficulties, the symptoms experienced can be divided into two, or even more, diagnoses, while for others, there is no diagnostic category into which they fit. These problems with our diagnostic categories make it difficult for researchers and doctors who want to know how and why, some people develop mental health difficulties, and how best to support them.

To solve these problems, we need to look at mental health difficulties in a different way. In the last five years, researchers have started using ‘person-centred’ statistical techniques, which produce an alternative to the diagnostic categories we use at the moment, to look at mental health difficulties in teenage groups. Person-centred techniques look for patterns in data that show how symptoms might group in certain ways for some individuals, and in different ways for others. For example, having poor concentration might be grouped together with feeling anxious and being withdrawn in some young people. In others, poor concentration might, instead, be grouped together with feeling restless and breaking rules. With traditional diagnoses, both sets of young people might be diagnosed with ADHD, but using a person-centred perspective we can find these different groupings that reflect the variety of difficulties being experienced. This should give researchers a better chance of understanding what might make it more (or less) likely that somebody has the problems they do, and what type of support might help them most.

The challenge we face is that person-centred techniques are still quite new and we don’t yet know whether the new groupings they produce are consistent, or any more representative or useful than the current ways we diagnose. This is what this project aims to assess. At the same time, we want to get input from young people with experience of mental health difficulties as we do this. Phase 1 will start by understanding more from young people about their experiences of mental health difficulties and the diagnostic journey. We want to know what has been important to them, what they think might have influenced the symptoms they live with, and what sorts of things help make life easier. Researchers will use the understanding we gain from these sessions to plan how they will do the statistical analysis in phase two to make sure that it captures what is important to young people. Phase 2 will be the statistical analysis, shaped by Phase 1. We will use ALSPAC data, which has followed up thousands of people from childhood and through the teenage years, and use person-centred techniques to find new groupings with shared patterns of symptoms. We will then test the statistical strength and consistency of the new groupings, and use understanding gained from Phase 1 to see whether the new groupings can help us to learn more about the factors that impact mental health. In Phase 3, we want to come back to young people to see how far they feel the new perspectives on mental health difficulties that were generated in Phase 2 fit with their experiences. They can help us to see what will and won’t be an improvement over existing diagnoses, and can consider with us how the findings can be used to improve the diagnostic journey. During this phase, we also want to discuss the findings with groups who make decisions about how CAMHS runs, to identify positive ways to use the knowledge that has been generated.

Impact of research: 
This project will benefit young people living with mental health conditions in a number of ways. In the short-term it would give those in charge of mental health services some ideas about what is important to consider during diagnosis and management, and a new way to look at mental health difficulties. Longer term, this can be used to inform a diagnostic process that truly reflects the pattern of difficulties individuals have. From a research perspective, we hope that in the short-term, our project will make any benefits of using person-centred techniques to define mental health difficulties clearer to researchers, so that they can use them effectively. With this understanding, knowledge of new ways to prevent and support these difficulties will be possible long-term. Adolescent mental health research will also benefit from the way this project combines the experiences of young people with complicated statistical analysis. Usually, these two parts of research are kept separate, but we want to show how much more we can understand if we bring the two together, and give other researchers an example that they can follow of how to do this effectively.
Date proposal received: 
Thursday, 16 December, 2021
Date proposal approved: 
Monday, 20 December, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Eating disorders - anorexia, bulimia, Mental health, Computer simulations/modelling/algorithms, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Statistical methods

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