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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B4115 - Adverse Childhood Experiences and Violent Offending - 09/08/2022

B number: 
B4115
Principal applicant name: 
Umar Toseeb | University of York (United Kingdom)
Co-applicants: 
Professor Nathan Hughes
Title of project: 
Adverse Childhood Experiences and Violent Offending
Proposal summary: 

Our proposed project is primarily centred on the research topic of diversion away from the criminal justice system. Specifically, we will chart the developmental interplay between person-centred clusters of adverse childhood experiences (ACEs) and violent offending (assault and use of a weapon) during adolescence. In doing this we hope to identify which clusters of ACEs are most salient for subsequent violent offending. We will also investigate whether these differ for marginalised groups.

Impact of research: 
We hope the findings will be used to divert at-risk children away from violent offending. As part of the project proposal, we have included plans to engage with relevant policy makers.
Date proposal received: 
Tuesday, 2 August, 2022
Date proposal approved: 
Tuesday, 9 August, 2022
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Childhood - childcare, childhood adversity

B4123 - Climate change sustainable diets and religion - 09/08/2022

B number: 
B4123
Principal applicant name: 
Dan Major-Smith | Population Health Sciences, University of Bristol
Co-applicants: 
Katie Major-Smith, Prof Jean Golding
Title of project: 
Climate change, sustainable diets, and religion
Proposal summary: 

Human activity is having a dramatic impact on our planet's climate, and measures to reduce carbon emissions to limit to extent of this climate change are urgently needed. In this project, using the recently-collected climate change data in ALSPAC we aim to explore the factors associated with climate change beliefs and behaviours, with a specific focus on both behaviours relating to sustainable diets (i.e., reduction of meat and/or dairy consumption) and religious/spiritual beliefs and behaviours (RSBB).

Impact of research: 
Study 1: To understand whether religion is associated with differences in climate change beliefs and behaviours, which may help understand why religious individuals are more/less likely to believe in climate change and engage in pro-environmental action. Study 2: In addition to understanding the factors associated with reducing meat/dairy consumption for environmental reasons, the identification of said factors may help inform future initiatives to target climate change interventions to previously-missed/hard-to-reach populations and to promote sustainable diets.
Date proposal received: 
Wednesday, 3 August, 2022
Date proposal approved: 
Tuesday, 9 August, 2022
Keywords: 
Social Science, Social science, Climate change; sustainable diets

B4103 - Quantifying the multi-system impact of antenatal maternal wellbeing across generations - 01/08/2022

B number: 
B4103
Principal applicant name: 
Kieran O'Donnell | Yale University
Co-applicants: 
Adelaide Feibel, Anna Lahdepuro, Adam Lombroso, Hung Pham, Dr. Vivette Glover, Dr. Thomas O'Connor, Dr. Marius Lahti, Dr. Katri Räikkönen
Title of project: 
Quantifying the multi-system impact of antenatal maternal wellbeing across generations
Proposal summary: 

Maternal antenatal anxiety, depression, and stress increase the risk for socioemotional and behavioral problems in childhood, effects which persist into early adulthood (O’Donnell et. al, 2014; Pearson et. al, 2013; Robinson et. al, 2008). These findings are consistent with the fetal origins of mental health hypothesis, which posits that exposures in utero contribute to individual differences in mental health outcomes across the lifespan (O’Donnell, Meaney, 2017).

While the association between antenatal maternal wellbeing and child development is well-established, much less is known about the multi-generational impact of antenatal maternal wellbeing on child health and development. Existing findings from multigenerational studies focus on birth weight (Lahti-Pulkkinen et. al, 2018; Drake et. al, 2015), and antenatal lead (Sen et. al, 2015) or diethylstilbestrol exposure (Kioumourtzoglou et. al, 2018)​​. Interestingly, mouse models have shown the multi-generational effects of stress or dietary manipulations on molecular characteristics of the offspring across multiple generations (Ward et. al, 2013; Radford et. al, 2014; Jawaid, Roszkowski, Mansuy, 2018).

In this proposal, we examine multi-generational effects of maternal well-being (encompassing mental and physical health) in an index pregnancy across 2 or more generations. Our analysis framework will consider important confounds including maternal and child genetic variation and will examine candidate biological processes for the transmission of risk e.g. variation in DNA methylation.

Impact of research: 
The association between maternal wellbeing during pregnancy and subsequent health outcomes in future generations has important clinical implications. Currently, most interventions related to maternal mental health are targeted at mothers after they give birth due to increased awareness surrounding postpartum depression. However, evidence of a negative effect of antenatal maternal distress across multiple generations on health outcomes would further underline the need to start mental health interventions earlier during pregnancy.
Date proposal received: 
Thursday, 21 July, 2022
Date proposal approved: 
Monday, 1 August, 2022
Keywords: 
Developmental biology, Developmental disorders - autism, Learning difficulty, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Offspring, Birth outcomes, Development, Epigenetics, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Hormones - cortisol, IGF, thyroid

B4114 - Social determinants of mental health and cognition in adolescence - 01/08/2022

B number: 
B4114
Principal applicant name: 
Susanne Schweizer | University of New South Wales & University of Cambridge (Australia)
Co-applicants: 
Karina Grunewald, Jasmin Wertz
Title of project: 
Social determinants of mental health and cognition in adolescence
Proposal summary: 

One quarter of the world’s population is affected by a mental or neurological disorder at some point in their life (WHO, 2001), and depression alone is predicted to be the leading burden of disease globally by 2030 (Malhi & Mann, 2018). These disorders typically manifest early in life, with 74% of diagnoses first occurring under the age of 18 years, and 50% before 15 years (Kim-Cohen et al., 2003). Understanding risk and protective factors underlying mental ill-health, and how these might develop over time, is crucial for the creation of effective prevention and intervention.

As children mature into adolescents, they increasingly interact with, and become more sensitive to evaluation and rejection by peers. Increased sensitivity to social rejection during this period has been associated with decreased mental health (Gao et al., 2017), while the opposite has been found for increased social support (van Harmelen et al., 2017). The environment in which these interactions occur is also changing, with adolescents spending an average of 6 hours each day online, the majority of which is spent on social media sites (Anderson & Jiang, 2018). Exploring these effects cross-sectionally, we found that increased social rejection sensitivity and decreased perceived social support were associated with increased negative mood in adolescents (11-24 years; Grunewald, Deng, Wertz & Schweizer, Under review), and now seek to further investigate these effects longitudinally.

Impact of research: 
In addition to expanding existing literature investigating the effects of risk and protective factors for young people’s mental well-being and cognition, our research will also enable a more nuanced understanding of the potential impacts of screen time usage on these outcomes.
Date proposal received: 
Thursday, 21 July, 2022
Date proposal approved: 
Monday, 1 August, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Cognition - cognitive function, Development, Statistical methods

B4121 - Mechanisms linking the natriuretic peptide receptor-C gene to elevated blood pressure Genetic epidemiology study - 01/08/2022

B number: 
B4121
Principal applicant name: 
Zoe Adams | School of Physiology, Pharmacology & Neuroscience, University of Bristol (United Kingdom)
Co-applicants: 
Dr Carolina Borges, Dr Alba Fernandez-Sanles, Dr Emma Hart
Title of project: 
Mechanisms linking the natriuretic peptide receptor-C gene to elevated blood pressure: Genetic epidemiology study.
Proposal summary: 

Previous research has identified several regions of the human genome associated with high blood pressure. One such region is the NPR3 gene, encoding the natriuretic peptide receptor-C. Whilst genetic variants in this region are associated with high blood pressure, it is not known which variant/s drive the association or whether the effect on blood pressure occurs through altered expression of the NPR3 gene. This study will use existing ALSPAC data to investigate the association between the NPR3 gene and high blood pressure.

Impact of research: 
This study will provide insights into the mechanism underlying the association between the NPR3 gene and elevated blood pressure, with the ultimate goal of determining whether the NPR3 gene is a potential target for treatment of hypertension. The outcomes of this study will inform a related physiological study which aims to assess the effect of NPR3 genotype on regulation of blood pressure and vascular tone (a separate future ALSPAC proposal).
Date proposal received: 
Monday, 1 August, 2022
Date proposal approved: 
Monday, 1 August, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Hypertension, GWAS, Statistical methods, Cardiovascular, Genetic epidemiology, Mendelian randomisation

B4109 - Childhood adverse events and breastfeeding associations with pregnancy behaviour and infant outcomes - 29/07/2022

B number: 
B4109
Principal applicant name: 
Rita Amiel Castro | University of Zurich (Switzerland)
Co-applicants: 
Vivette Glover, PhD, Thomas O'Connor, PhD, Ulrike Ehlert
Title of project: 
Childhood adverse events and breastfeeding: associations with pregnancy behaviour and infant outcomes
Proposal summary: 

Adverse childhood experiences have been associated with unfavorable health behaviours, somatic and psychological complaints in pregnancy. Beyond pregnancy experiences, a large body of research highlights intergenerational effects of maternal history of early trauma on their offspring. Given the growing interest on early adversity consequences during the perinatal phase, we aim to examine the associations between traumatic childhood events and pregnancy health behaviour, psychological symptoms, birth outcomes, sociodemographics and breastfeeding. For this we intend to include mother-infant pairs from the Avon Longitudinal Study of Parents and Children. Adverse childhood events consist of abuse (e.g. emotional, physical and sexual), neglect, (e.g. emotional and physical) and household dysfunction (e.g. parental mental illness, divorce or incarceration). We measure pregnancy health behaviour (e.g. exercise, smoking, alcohol, BMI), psychological symptoms (e.g. anxiety and depressive symptoms), sociodemographics (e.g. education, social class) and breastfeeding (e.g.initiation and duration).

Impact of research: 
Considering that a recent review on early traumatic events and breastfeeding was only able to find 8 studies in the topic, from those, 6 were qualitative and no clear conclusion was reached, it is clear that more research is needed. We believe our study will have the potential to inform readers and the scientific community about the associations between those topics.
Date proposal received: 
Wednesday, 27 July, 2022
Date proposal approved: 
Friday, 29 July, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Nutrition - breast feeding, diet

B4110 - Genetic evidence for the causal relationship between 25OHD and bone fracture a non-linear Mendelian randomization analysis - 18/07/2022

B number: 
B4110
Principal applicant name: 
David Hughes | University of Bristol, MRC-IEU (UK)
Co-applicants: 
Dr. Lucy Goudswaard, Madeleine Smith, Nicholas Timpson, Dr Steven Burgess
Title of project: 
Genetic evidence for the causal relationship between 25(OH)D and bone fracture: a non-linear Mendelian randomization analysis
Proposal summary: 

While previous studies have demonstrated no clear effects of vitamin D upon risk of fracture and lowered BMD in the general population, it is clear that vitamin D deficiency causes increased risk of fracture and a reduction in BMD, as is seen in rickets. Further, RCTs of high dose vitamin D have shown a decrease in BMD after administration of vitamin D. This suggests that the effects of vitamin D upon BMD and perhaps fracture are non-linear.

We therefore propose non-linear MR studies of the effect of vitamin D (as measured by 25(OH)D) on BMD and fracture outcomes. Such findings could help to guide future RCTs and provide clinicians with some insights as to the utility of vitamin D administration in different segments of the population.

Impact of research: 
It will help elucidate the impact vitD deficiency has on bone health in the general European population.
Date proposal received: 
Monday, 18 July, 2022
Date proposal approved: 
Monday, 18 July, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Bone disorders - arthritis, osteoporosis, GWAS, Medical imaging, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Bones (and joints), Equipment - MRI, Genetic epidemiology, Mendelian randomisation, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B4111 - Research methods in human epigenetics - 18/07/2022

B number: 
B4111
Principal applicant name: 
Lara Choksey | Wellcome Centre, University of Exeter
Co-applicants: 
Title of project: 
Research methods in human epigenetics
Proposal summary: 

This project looks at methods used in research on human epigenetics, particularly around uses of
sociological and psychological data in devising research questions.

All paperwork stored in relevant B number folder

Impact of research: 
Date proposal received: 
Monday, 18 July, 2022
Date proposal approved: 
Monday, 18 July, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B4107 - Fathers preconception smoking and offspring DNA methylation A population-based two generation study - 18/07/2022

B number: 
B4107
Principal applicant name: 
Matthew Suderman | IEU, Bristol Medical School (UK)
Co-applicants: 
Professor Jean Golding, Dr Sarah Watkins, Professor John Holloway, Dr Negusse Kitaba
Title of project: 
Fathers’ preconception smoking and offspring DNA methylation: A population-based two generation study
Proposal summary: 

Animal experiments suggest that exposure to toxins such as found in cigarette smoke may impact respiratory health across generations. Studies in humans are however limited. In this study, we ask if gene activity differs in children whose fathers smoked prior to them being conceived. Differences have been observed in participants of the RHINESSA study. Here we ask if similar differences are observed in ALSPAC participants.

Impact of research: 
Better understanding of the effects of paternal smoking on offspring.
Date proposal received: 
Tuesday, 12 July, 2022
Date proposal approved: 
Monday, 18 July, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Microarrays, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics, Fathers, Genetic epidemiology

B4101 - Sensitive periods for the effects of depression on suicide risk - 18/07/2022

B number: 
B4101
Principal applicant name: 
Alexandre A Lussier | Massachusetts General Hospital (United States)
Co-applicants: 
Dr. Erin C. Dunn
Title of project: 
Sensitive periods for the effects of depression on suicide risk
Proposal summary: 

Depression is one of the most important risk factors for suicide. Almost 60% of people who die by suicide experienced depression at some point in their life. Yet, it remains unclear why only certain people with depression eventually become suicidal. Recent evidence suggests there are sensitive periods in development when life experiences, such as depression, can have stronger effects on mental illness. It is also well documented that suicidality results from both life experiences and genetic risk.
However, most studies of genetic risk for suicide, depression, and subsequent suicidal suicidality focus on people measured at a single timepoint. This limitation prevents us from 1) identifying people who are at the highest risk for future suicidal behaviours and 2) developing timely and effective interventions that prevent suicide in people with depression. As such, this project will use longitudinal data from two birth studies to determine when and how genetic risk and experiences of depression during childhood and adolescence influence suicide risk in early adulthood.
First, we will identify the specific ages and patterns of depression during childhood and adolescence that most predispose young adults to suicide. These results will help us build and implement interventions that are positioned at the best possible time to prevent suicide risk among youth affected by depression.
Second, we will determine whether children and adolescents with increased genetic risk for suicide or mental illness are more likely to become suicidal after experiencing depression at specific ages. These findings will improve our ability to identify youth who are at greater risk for suicide and provide insight into the genetic pathways leading to suicide.
Third, we will identify biological mechanisms that explain the link between depression and suicide. We will focus on epigenetic changes, as they are linked to human health and are thought to reflect both life experiences and genetics. Thus, they may represent a biological pathway through which suicide risk can become “molecularly programmed”. Identifying epigenetic changes that link depression to suicide risk will help guide the development of biomarkers that will allow us to identify at-risk youth quickly and effectively.
In sum, this project will highlight key periods and biological targets that can be used to predict and prevent suicidality among childhood and adolescents who experience depression. These will ultimately catalyse better interventions that prevent suicide in young adults.

Impact of research: 
Through this research, we will determine whether the timing of depression during development can predict future suicidality, as well as identify specific genetic and epigenetic mechanisms that might influence the relationship between depression and suicide risk. Specifically, this interdisciplinary study will identify (1) specific ages and patterns of depression during childhood and adolescence that increase future suicidality; and (2) genetic and epigenetic profiles that predict suicidality and link depression to suicide risk. Ultimately, these efforts will highlight developmental windows and biological mechanisms that can be targeted in interventions to reduce suicide risk among people who experience depression.
Date proposal received: 
Friday, 8 July, 2022
Date proposal approved: 
Monday, 18 July, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Computer simulations/modelling/algorithms, GWAS, Statistical methods, Epigenetics, Genetics, Genomics

B4108 - Special collections Eating disorders in Britain 1980-2010 - 13/07/2022

B number: 
B4108
Principal applicant name: 
Alice Weinreb | Loyola University Chicago, USA (USA)
Co-applicants: 
Title of project: 
Special collections: Eating disorders in Britain, 1980-2010
Proposal summary: 

I am interested in the ways in which eating disorders were being discussed (both popularly and amongst academics/practitioners) and researched in the late 20th/early 21st century. I’m especially interested in ALSPAC because of the specific interest in the impact on eating disorders on maternity (a relatively unusual approach at the time.) I am only interested in material on the eating disorder research components of ALSPAC

Impact of research: 
Date proposal received: 
Wednesday, 13 July, 2022
Date proposal approved: 
Wednesday, 13 July, 2022
Keywords: 
Eating disorders, Eating disorders - anorexia, bulimia

B4104 - UKLLC Multi-Longitudinal Cohort Study into occupational factors and COVID Risk as part of PROTECT National Core Study - 12/07/2022

B number: 
B4104
Principal applicant name: 
Matthew Gittins | Mancheter
Co-applicants: 
Title of project: 
UKLLC: Multi-Longitudinal Cohort Study into occupational factors and COVID Risk as part of PROTECT National Core Study
Proposal summary: 

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

Impact of research: 
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
Date proposal received: 
Tuesday, 12 July, 2022
Date proposal approved: 
Tuesday, 12 July, 2022
Keywords: 
Social Science

B4105 - UKLLC Using metabolomics to better understand COVID-19 symptoms - 12/07/2022

B number: 
B4105
Principal applicant name: 
Francisco Perez-Reche | University of Aberdeen
Co-applicants: 
Title of project: 
UKLLC: Using metabolomics to better understand COVID-19 symptoms
Proposal summary: 

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

Impact of research: 
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
Date proposal received: 
Tuesday, 12 July, 2022
Date proposal approved: 
Tuesday, 12 July, 2022
Keywords: 
Immunology

B4106 - UKLLC Harmonised Core Socio-demographic Measures Dataset - 12/07/2022

B number: 
B4106
Principal applicant name: 
Dara O’Neill | UCL
Co-applicants: 
Title of project: 
UKLLC: Harmonised Core Socio-demographic Measures Dataset
Proposal summary: 

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

Impact of research: 
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
Date proposal received: 
Tuesday, 12 July, 2022
Date proposal approved: 
Tuesday, 12 July, 2022
Keywords: 
Immunology

B4094 - The relationship between maternal mental health and substance use in adolescence - 29/07/2022

B number: 
B4094
Principal applicant name: 
Mhairi London | University of Glasgow (United Kingdom)
Co-applicants: 
Miss Jovana Kablar
Title of project: 
The relationship between maternal mental health and substance use in adolescence.
Proposal summary: 

Previous research has established the effects of maternal mental health on children and adolescents MH but there is limited evidence on the association between maternal mental health and risky behaviours in adolescence, such as substance use (Campbell et al., 2009; Pearson et al., 2013). Studies have demonstrated that depressed parents played a significant part in offspring’s MH and substance use in adolescence and adulthood (Weissman et al., 2006). These results have been replicated by Flouri and Ioakeimidi (2008) finding that adolescents, particularly male, engaged in more risky behaviours, including alcohol use, when their mothers had chronically high or increased depressive symptoms, compared to those that their mothers never experienced depression. Wickham and colleagues (2015) also showed that adolescents who were exposed to maternal depressive symptoms in middle childhood showed a stronger association with using common substances (alcohol, cigarettes, and marijuana) and earlier engagement in such behaviours, including hallucinogenic use. This project aims to extend the evidence and look at different maternal mental health conditions and their relationship with substance use in adolescence using the ALSPAC data.

Impact of research: 
The findings from this research project will help researchers understand how early maternal experiences can impact risky behaviours in adolescence. The results could provide guidance for prevention and promotion strategies targeting substance use in adolescence.
Date proposal received: 
Thursday, 7 July, 2022
Date proposal approved: 
Monday, 11 July, 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, Statistical methods, Growth, Mothers - maternal age, menopause, obstetrics, Offspring, Parenting, Psychology - personality, Maternal mental health, substance use, adolescence,

B4091 - Cannabis use and mental health a genetically informed study - 11/07/2022

B number: 
B4091
Principal applicant name: 
Massimiliano Orri | McGill University (Canada)
Co-applicants: 
Natalie Castellanos Ryan, Dr., Michel Boivin, Dr., Mara Brendgen, Dr., Sylvana Côté, Dr., Isabel Fortier, Dr., Marie-Claude Geoffroy, Dr., Milica Miocevic, Dr., Isabelle Ouellet-Morin, Dr., Richard Tremblay, Dr., Gustavo Turecki, Dr.
Title of project: 
Cannabis use and mental health: a genetically informed study
Proposal summary: 

Cannabis use in youth is an important public health concern, especially as it often starts in young teens and in light of recent changes in Canadian legislation. The possible effects of cannabis (marijuana, weed, etc.) use on mental health are poorly understood. Cannabis is known to be associated with later psychosis. But what about more common mental health problems like depression, anxiety, and suicidal thoughts or attempts? Our first objective is to clarify the associations, if any, between cannabis use and later anxiety, depression, and suicidality, and whether they are causal or simply associative. Our second objective is to test the genetics-environment link – whether youth with pre-existing vulnerability to mental health problems are more at risk of depression, anxiety, and suicidality if they use cannabis, while the risk remains low for others. We will use data from the ALSPAC population-based longitudinal cohort. Participants had been asked at various times whether, how often, and when they started using, as well as questions on their mental health. Data will be analyzed by robust approaches to provide strong evidence in support (or not) of the links between cannabis use and later depression, anxiety, and suicidality. Clinically relevant patterns of cannabis use will be examined: a) ever used, b) age at onset, and c) intensity. Our findings will allow clinicians, researchers, and policymakers to develop better prevention and treatment programs to avoid mental health consequences of cannabis use in young people.

Impact of research: 
To clarify the nature of the associations between cannabis use and depression, anxiety, and suicidality, respectively, taking advantage of genetically informed population-based designs. This would inform on whether prevention of cannabis use may reduce the risk of these mental health problems in youth.
Date proposal received: 
Thursday, 23 June, 2022
Date proposal approved: 
Monday, 11 July, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Genetic epidemiology

B4099 - Is sexual violence in early adulthood among women associated with subsequent alcohol misuse later in life - 11/07/2022

B number: 
B4099
Principal applicant name: 
Hannah Sallis | MRC IEU
Co-applicants: 
Claudia Barber, Professor Marcus Munafo
Title of project: 
Is sexual violence in early adulthood among women associated with subsequent alcohol misuse later in life?
Proposal summary: 

Within the United Kingdom the prevalence of women’s experience of sexual violence particularly in early adulthood is evidenced to be at an increasing rate (Borumandnia et al., 2020) and much higher than society displays. Reports to clinics of the consequential physical and psychological effects have led to an interest from researchers to further investigate the prominent consequential risks following an experience of sexual violence. Interest has risen around incidents of alcohol misuse over other substances following a woman’s experience of sexual violence, as a result of the accessibility and social acceptance accompanying the substance (Burnam et al., 1988). Additionally, consequent severe health risks have been linked to the misuse of alcohol which may lead to an endurance of health concerns for the individual as well as the subsequent pressure implemented onto the health services.

However, despite the prevalence of sexual violence and consequent health risks associated with alcohol misuse, a lack of consistent evidence dominates existing literature. A myriad of reasons as to why a lack of consistent evidence prevails, however consistent reference to the small sample sizes due to the diverse population, methodological complications and inadequate measures are the most prominent throughout existing literature. Furthermore, due to the ambiguous nature of both sexual violence and alcohol misuse, difficulties can arise when attempting to define the two concepts, particularly when portraying this to patients, which can influence accuracy of the data gathered. Nonetheless, a consistent effort is made to reduce these confounding factors to produce research that can reap both clinical and educational benefits from the knowledge gathered. This project aims to account for the issues that previous research has struggled to address, through focusing on the gap in the literature through the use of the large ALSPAC data set to investigate whether an association exists between women’s early adulthood experience of sexual violence in early adult hood at aged 16 and their subsequent alcohol use at ages 24.

Impact of research: 
I believe the impact of this current research will be beneficial for many of reasons, from both a clinical standpoint and as a way of expanding the existing literature to strive for a more comprehensive understanding of such a complex yet common association. Although widespread research has been carried out to establish whether an association exists between early adulthood experience of sexual violence and subsequent alcohol misuse, the complexity of the relationship also increases. This is as a result of the increased accessibility that young adults have to both sexual experiences and alcohol, as well as the confounding variables that exist when measuring an individual’s alcohol misuse. Additionally, evidence from a longitudinal community study from Fergusson et al (1996) found that individuals who experience sexual violence in early adulthood are associated with increased risk of developing psychiatric problems as well as consequential physical health problems. This highlights the far-reaching effects that can arise as a result of an individual’s experience of exposure to sexual violence. Therefore, contribution from the research derived from this project can acknowledge the importance that early intervention can have on reducing financial and resourceful pressure throughout healthcare services as well as minimising patient risk of developing additional health issues. Furthermore, contributing to the existing research around this topic to further confirm whether an association exists is important from an educational perspective as it may be able to provide clinicians with an insight the risks that may occur, from both a patient that has experienced exposure to sexual violence and those that may be vulnerable to victimisation of sexual violence due to their alcohol misuse. Through a more comprehensive understanding, safeguarding strategies can be implemented to ensure the risk factors of the bi-directional relationship between alcohol misuse and exposure to sexual violence can be reduced. Furthermore, research suggests that individuals who experience alcohol misuse problems may be at higher risk of experiencing revictimization (Coid et al., 2011), which emphasises the need for knowledge to facilitate safeguarding procedures.
Date proposal received: 
Friday, 1 July, 2022
Date proposal approved: 
Monday, 11 July, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods

B4100 - Validation of novel biomarkers in pre-diagnostic brain tumour bloods and potential correlation with tumour biomarkers - 29/07/2022

B number: 
B4100
Principal applicant name: 
Kathreena Kurian | University of Bristol (England)
Co-applicants: 
Miss Lily Andrews, Miss Amy Howell , Mr Zak Thornton
Title of project: 
Validation of novel biomarkers in pre-diagnostic brain tumour bloods and potential correlation with tumour biomarkers.
Proposal summary: 

Around 60,000 patients in the UK are living with a brain tumour. Brain tumours are the most frequent solid tumour type in children and young adults, second only to leukaemias. Overall, less than 20% of brain tumour patients survive 5 years or more after diagnosis, and brain tumours are responsible for the most years of life lost of any cancer type. In the UK in 2013: 38 % of brain tumour patients visited their GP 5 times or more before referral to secondary care for diagnosis by imaging MRI/CT scan and neurosurgical biopsy because the symptoms such as headache are non-specific. There is an urgent need to develop new sensitive tests of brain tumours to help GPs in primary care.

A simple blood test performed by a GP in the clinic would aid decision-making and
early diagnosis. This would revolutionize care by speeding up diagnosis, reducing costs and anxiety of unnecessary scans and reducing the number of patients presenting with inoperable
large brain tumours. Moreover, this test could be used as an early monitor of brain tumour
recurrence.

Impact of research: 
These biomarkers could be used to develop blood tests for early diagnosis of brain tumours.
Date proposal received: 
Monday, 4 July, 2022
Date proposal approved: 
Wednesday, 6 July, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Cancer, GWAS

B4098 - Heart failure with preserved ejection fraction during mid-life in women with previous hypertensive pregnancy - 08/07/2022

B number: 
B4098
Principal applicant name: 
Paul Leeson | University of Oxford (RDM Cardiovascular Medicine) (United Kingdom)
Co-applicants: 
Dr Megha Agarwal
Title of project: 
Heart failure with preserved ejection fraction during mid-life in women with previous hypertensive pregnancy
Proposal summary: 

Women who develop high blood pressure during pregnancy are at substantial risk of future cardiovascular disorders, which emerge earlier in life than for women who have pregnancies without high blood pressure or complications related to this. Of particular concern, recent evidence highlights that high blood pressure during pregnancy doubles the risk of hospitalisation for heart failure, specifically, heart failure with preserved ejection fraction (HFpEF). Once established, changes in the heart underlying HFpEF are difficult to modify and prevention is considered a priority. However, we, and others, have shown changes in the heart consistent with early HFpEF are already evident following a pregnancy complicated by high blood pressure, before significant exposure to other known risk factors for HFpEF such as long-standing hypertension and diabetes.
Therefore, to understand whether there is a clinical rationale for pregnancy-related interventions to prevent later HFpEF we propose, firstly, to follow up the original maternal G0 cohort from the Avon Longitudinal Study of Parents and Children to determine whether high blood pressure during pregnancy remains independently associated with the presence of sub-clinical and clinical HFpEF in later life. Secondly, we will use cardiovascular magnetic resonance and echocardiography imaging techniques to characterise the changes and clinical features observed in the heart in this group. Finally, we will identify key biomarkers in the heart that are clinically relevant to the phenotype of HFpEF associated with high blood pressure during pregnancy. We will then study these biomarkers in other trials we currently have in progress that are using interventions earlier in life to try and prevent disease.
An additional anticipated feature of this project is the synergistic opportunity to link the imaging data we will collect in the maternal cohort of ALSPAC with our ongoing CLARITY study that is undertaking similar imaging of the ALSPAC G1 cohort of adults born to these pregnancies. We hope to link the imaging findings from the mothers and their children between cohorts to determine whether they share distinct familial patterns of cardiac remodelling.

Impact of research: 
The ultimate objective is to be able to better characterise the trends in disease progression in women exposed to hypertensive pregnancies as well as the role of early intervention. As such, the novel findings generated by our study are likely to have direct relevance for clinical care pathways.
Date proposal received: 
Thursday, 30 June, 2022
Date proposal approved: 
Wednesday, 6 July, 2022
Keywords: 
Clinical research/clinical practice, Hypertension, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Medical imaging, Blood pressure, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Equipment - MRI, Physical - activity, fitness, function

B4097 - Investigating the impact of variation in BMI on the metabolome using multiple study designs - 29/06/2022

B number: 
B4097
Principal applicant name: 
Laura Corbin | MRC IEU, University of Bristol (UK)
Co-applicants: 
Maddy Smith, Dr David Hughes, Professor Nic Timpson
Title of project: 
Investigating the impact of variation in BMI on the metabolome using multiple study designs
Proposal summary: 

Obesity is known to have effects on cellular metabolism, which is reflected in a person’s circulating metabolome. Metabolomics, defined as the measurement and study of circulating small molecules that are the substrates and products of cellular metabolism, is increasingly used by epidemiologists to provide a functional read-out of bulk cellular activity and a proxy to individual current health. This approach also provides insight into biological pathways linking exposures and disease.

Measuring the metabolome of people with measured body mass index (BMI) allows us to look for ways in which BMI affects the metabolome. Metabolites found to be associated with BMI can then be further investigated and linked to cellular pathways – knowledge which will help us to understand the pathology of obesity. We have already begun to look at how bariatric surgery (within the By-Band-Sleeve trial (BBS), https://bristoltrialscentre.blogs.bristol.ac.uk/details-of-studies/by-ba...) and non-surgical weight loss interventions (within the DiRECT trial, https://www.directclinicaltrial.org.uk/) affect the metabolome, and we want to use the recall-by-genotype (RbG) Metabolon data in ALSPAC (https://onlinelibrary.wiley.com/doi/full/10.1002/oby.23441) to compare our results to population-level data. Bringing together data from these different study designs enables to unpick the metabolomic effects that are associated with BMI and their relevance to disease.

Impact of research: 
Characterising the metabolomic effect of BMI variation will lead to better understanding of the pathology of obesity and its related diseases.
Date proposal received: 
Monday, 27 June, 2022
Date proposal approved: 
Tuesday, 28 June, 2022
Keywords: 
Epidemiology, Diabetes, Obesity, Mass spectrometry, Metabolomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., BMI, Genetic epidemiology, Statistical methods

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