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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B4125 - Determining the association between trauma HPA axis dysregulation and mental health using robust measures - 01/09/2022

B number: 
B4125
Principal applicant name: 
Hannah Jones | University of Bristol (UK)
Co-applicants: 
Professor Stan Zammit, Professor Golam Khandaker
Title of project: 
Determining the association between trauma, HPA axis dysregulation and mental health using robust measures
Proposal summary: 

Poor mental health affects more than one billion people worldwide but despite this frequent occurrence and the potential personal burden, treatment options are scarce and not always effective. There is a need, therefore, for a better understanding of the environmental and biological causes of mental health problems, so that new treatments can be developed.
It is known that stressful or traumatic situations can increase an individual’s chance of developing a range of mental health problems. In response to a stressful situation, whether psychological or physical, the human body activates processes that aim to increase the chance of survival. These responses are referred to as “fight-flight-freeze” and can result in giving the body energy, making you feel more, and reducing the sensation of pain. One key hormone involved in this response is cortisol. Although the release of cortisol in response to stress is initially beneficial, evidence has shown that experiencing severe or ongoing stressful events can lead to abnormal cortisol levels, which in turn has been linked to harmful outcomes, including obesity, cancer, heart disease, susceptibility to infection, and poor mental health.
Mental health problems that have been linked to cortisol levels include psychosis, depression, anxiety, and post-traumatic stress disorder (PTSD). For example, studies have shown that individuals diagnosed with depression or schizophrenia have higher levels of cortisol in their blood or saliva when compared to individuals without a psychiatric illness, while individuals with PTSD have lower levels. Some studies also show that high cortisol levels in early life associate with developing a mental health problem later in life, indicating that stress response abnormalities may cause mental health problems. However, findings are not always consistent, and results are hard to compare as the time of day the cortisol measure is taken and the material used for measurement (e.g., saliva, blood, urine) vary across studies.
One way in which cortisol may be causally linked to mental health problems is through inflammation. In normal conditions, cortisol reduces inflammation (e.g., it’s commonly used to treat inflammatory diseases such as arthritis and asthma), however, studies have shown that under abnormal conditions (e.g., during ongoing stress), the relationship changes and high levels of cortisol are associated with increased inflammation. An increase in inflammation can be harmful to neurons in the brain by affecting neuron functioning and decreasing neuron repair. As such, studies have linked stress-related inflammation to poor mental health, however, the size of these studies are small and, again, studies are hampered by inadequate measures of cortisol and inflammation.
As can be seen, there is a need for large studies using improved measures of cortisol to investigate the causal link between stress response and mental health. In this project we therefore aim to generate reliable, robust measures of cortisol and inflammation using serum measures, genetic data and hair samples, to investigate whether cortisol levels lie on the pathway between early life trauma and mental health and whether they influence inflammation.
This work will inform whether interventions targeting the stress response system have the potential to prevent or treat psychiatric disorders.

Impact of research: 
This research will improve our understanding of the role of the body’s stress response in the relationship between trauma and mental health, as well as in priming patterns of inflammation during childhood and adolescence. The hair cortisol measures and longitudinal inflammatory patterns derived by this study will serve as a useful resource for other researchers interested in cortisol and inflammation levels during the life-course. More specifically, findings from this research will inform whether stress response could be a target for treatment, prediction and prevention of mental health problems in young people. Findings could be used to direct future work investigating characteristics of cortisol and inflammation-related mental health and clinical trials of cortisol/immuno-modulating therapies for psychiatric disorders.
Date proposal received: 
Thursday, 11 August, 2022
Date proposal approved: 
Monday, 15 August, 2022
Keywords: 
Epidemiology, Mental health, Statistical methods, Genome wide association study

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

B4122 - AMOUNT An investigation of changes in young peoples substance use - 15/08/2022

B number: 
B4122
Principal applicant name: 
Rebecca Langella | Liverpool John Moores University (United Kingdom)
Co-applicants: 
Harry Sumnall, Laura Goodwin , Vivian Hope
Title of project: 
AMOUNT: An investigation of changes in young people's substance use
Proposal summary: 

Substance use (SU) by young people (YP; YPSU) can lead to short- and long-term harms. Although YPSU has been falling over the past 20 years in the UK, evidence suggests that it is now increasing again among some groups. Studies suggest that these changes may depend on where YP live, how they socialise, the health/social challenges that they face, and the ways in which they access and use substances.

This project is part of a larger study that is working with YP and other experts to understand in what ways and for which groups of YP SU is changing. We are developing and testing new theories to help us understand the most important factors that underpin these increases. Some factors relate to individuals, including mental health or experiences of the care system; others will relate to wider contexts such as communities, policy, and youth culture, including how drug markets have changed, changes in leisure and recreation, or shifts in attitudes towards SU; and others depend on the interactions between all of these.

In this project we will first examine whether there is evidence that YP may be using drugs to help cope with mental health problems. We will then explore whether YP who use alcohol and have mental health problems have worse outcomes if they also use drugs such as cannabis.

Impact of research: 
Our overall project (the AMOUNT study) of which this proposed study is an important component, was commissioned by the Department for Health and Social Care through the NIHR Policy Research Programme in response to concerns about rising youth drug use after two decades of decline. The project was specifically mentioned in the recent national Drugs Strategy (From Harm to Hope 2021) as informing subsequent activity in relation to youth drug use, including policy, practice, and further research funding calls. Our steering group comprises officials from relevant government departments/bodies, and our findings will be used to inform the activities of the cross-governmental Joint Combatting Drugs Unit.
Date proposal received: 
Monday, 1 August, 2022
Date proposal approved: 
Tuesday, 9 August, 2022
Keywords: 
Health Services Research/Health Systems Research, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Statistical methods, Social science

B4124 - Utilising Epigenetics as a Platform for Precision Medicine - 15/08/2022

B number: 
B4124
Principal applicant name: 
Dylan Kiltschewskij | The University of Newcastle (Australia)
Co-applicants: 
Dr William Reay, Professor Murray Cairns
Title of project: 
Utilising Epigenetics as a Platform for Precision Medicine
Proposal summary: 

Complex disorders such as psychiatric conditions often arise from varying combinations of genetic and environmental factors. This represents a major problem for drug development, as the cause of the disease is highly variable from person to person, and as such, drug response rates vary significantly. By examining an individual’s unique genetic risk factors, treatment response rates could theoretically be increased by improving subcategorization of individuals and personalising the administration of appropriate medications. Although genetic risk scores have been developed for this purpose, the use of epigenetic information in the form of DNA methylation remains relatively underexplored, despite the fact this epigenetic modification can simultaneously index both genetic and environmental risk factors. In this study, we will examine whether DNA methylation can be used to refine the classification individuals with complex disorders and better match affected individuals to personalised medications. In addition, we will also explore the relationship between epigenetic risk for complex disorders and measures of biochemical and metabolic traits to determine whether the epigenetic component of complex disorders is associated with changes in druggable, blood-based biomarkers.

Impact of research: 
This study will greatly enhance our understanding of epigenetic risk factors in complex disorders and its ability to inform on molecular classification of affected individuals. Furthermore, results from this study will provide insights into the application of epigenetic risk in precision medicine frameworks, an essential step in the development of improved treatment and prevention strategies across the spectrum of complex disorders.
Date proposal received: 
Thursday, 4 August, 2022
Date proposal approved: 
Tuesday, 9 August, 2022
Keywords: 
Molecular genetics and genomics, Mental health, Respiratory - asthma, Metabolomics, Statistical methods, Epigenetic analyses Genetics, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Genetics, Genomics, Metabolic - metabolism, Statistical methods, Complex disorders Psychiatric illness Asthma

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

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

B4118 - Intergenerational gut bacterial strain transfer - 15/09/2022

B number: 
B4118
Principal applicant name: 
Falk Hildebrand | Quadram Institute Bioscience (United Kingdom)
Co-applicants: 
Title of project: 
Intergenerational gut bacterial strain transfer
Proposal summary: 

The gut microbiome is important for human health, supporting nutrition, pathogen defence and immune homeostasis, with more than 200 species inhabiting each human gut. The majority of the hundreds of microbial species (Bacteria, Archaea, Fungi typically) colonizing each human gut were only recently characterized from metagenomic assembled genomes and new taxa are still being discovered. Systematic studies investigating how these diverse microbial ecosystems are transferred between humans and adapt to their hosts are so far large lacking. Describing dispersal strategies and microbial adaptation to the human host will significantly contribute to understanding and manipulating the gut microbiome to re-set the host health.

Impact of research: 
This research is fundamental science that is exploring so far unknown questions. Funded by an ERC starter grant, we will explore the wider research question how gut microbes disperse, what factors influence this process and in how far these microbes evolve during colonization. The likely impact are a much better understanding of bacterial colonization strategies and evolution during this process, enabling the development of new probiotics, gut microbial health and restoration projects and understanding the importance of the initial (mostly maternal) seeding of the gut microbiome.
Date proposal received: 
Wednesday, 27 July, 2022
Date proposal approved: 
Friday, 29 July, 2022
Keywords: 
Molecular genetics and genomics, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Diabetes, Eating disorders - anorexia, bulimia, Eczema, Gastrointestinal, Mental health, Obesity, DNA sequencing, Environment - enviromental exposure, pollution

B4120 - Investigation of impacts of colour blindness on educational and psychological outcomes - 22/08/2022

B number: 
B4120
Principal applicant name: 
Gabriele Jordan | Newcastle University (UK)
Co-applicants: 
Ms Cat Pattie, Prof Satnam Dlay
Title of project: 
Investigation of impacts of colour blindness on educational and psychological outcomes
Proposal summary: 

Colour blindness (CVD) is a congenital condition affecting 8% of men (0.4% of women). Depending on type and severity, affected individuals have significant difficulties discriminating a wide range of colours facing wide-ranging challenges on a day-to-day basis (e.g. interpreting colour-coded information at the workplace or recreational environments). A growing impact is expected in educational settings due to an increasing reliance on colour resources in schools. Unfortunately, a study using a birth cohort from 1958 (Cumberland et al, 2004) has reported a lack of impact of colour blindness on Maths and reading ability but fails to account for the increase in colour in classrooms in recent years. Regrettably the publication led to the cessation of CVD school screening in 2009, preventing children from accessing more appropriate resources.
In contrast, a number of authors have argued that CVD can increase difficulties experienced in a range of school subjects including Sciences, Maths, Art, PE and Geography as such subjects may use colour to explain concepts, give instructions and require it in problem solving tasks. Alongside any academic implications, CVD has been found to have an effect on social, psychological and emotional outcomes. For example CVD children may experience teasing from classmates.
We here propose to investigate the potential impacts of CVD on education and emotional outcomes in a more recent cohort.

Impact of research: 
One of the single most important reasons for doing this study is the contribution it will make to change the current Government policy on screening for colour-vision deficiencies in schools. The detection of CVD children early in their education will enable teachers to seek out more appropriate resources and help alleviate day-to-day challenges currently prevalent in the educational sector. Publication of the study, more generally, will raise awareness of the problems CVD schoolchildren face, and might increase the likelihood of schools engaging with appropriate teacher training programmes that are already offered by organisations such as colourblindawareness.org. Strategies can then be developed to help CVD schoolchildren with their learning.
Date proposal received: 
Friday, 29 July, 2022
Date proposal approved: 
Friday, 29 July, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Learning difficulty, Statistical methods, Vision

B4092 - The Relationship Between Identifiable Health Risk Behaviours And the Development of Severe Mental Illness Within A Syndemic Fram - 22/08/2022

B number: 
B4092
Principal applicant name: 
Emily Peckham | University of York, Health Sciences (Mental Health and Addiction Research Group) (United Kingdom)
Co-applicants: 
Ms Silke Vereeken
Title of project: 
The Relationship Between Identifiable Health Risk Behaviours And the Development of Severe Mental Illness Within A Syndemic Fram
Proposal summary: 

We want to find out in what way everyday habits and behaviours actually can change how people with a severe mental illness experience this illness, and, by finding that out, how we can possibly advise people, GPs, and the government in helping people feel better and live a better life they enjoy more in the long term. To do that, we are collecting information on how active a person with one of three specific mental illnesses keeps; how often they spend time outside, like in a garden, park or forest; how well and how much they sleep; whether they smoke or drink alcohol, and if so how much and when or when not; and how resilient they are personally to the bad or sad things that can happen in life, like having to move or losing their job or a loved one dying. We then try to find out how likely for example a highly active person with for example bipolar disorder is to also spend a lot of time outside in a park or garden, and how likely they are to sleep better and more hours during the night, and whether they smoke or drink alcohol (a lot) or not. And then we check whether them being so active changes how bad they feel with regards to their mental illness, and how their mental illness affects them. And we do the same thing for people with schizophrenia and severe depression. The idea behind it is that all these habits and behaviours make another habit or behaviour more or less likely to happen, so a person who is highly active would technically also be less likely to smoke a lot. And smoking a lot makes it very likely that if you have depression, you don't feel very good and experience a lot of negative feelings, more so than a person with depression who doesn't smoke. We'll be working on this for three years, building a blueprint-model on this collection of information, and then test how strong this model is on other datasets. And if we're right and we can find a strong model of influencing behaviours and habits, then we can use this model to help councils and the government give out better information on how to help make people live a healthier and better life for themselves.

Impact of research: 
With the outcomes of this project, we contribute to the novel research interest of syndemics in mental health care. The findings will be substantial in guiding future health policies, improving the current health care system, de-stressing and unburdening overworked health care staff, and in supporting people with SMI to lead healthier, happier lives.
Date proposal received: 
Thursday, 28 July, 2022
Date proposal approved: 
Friday, 29 July, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Computer simulations/modelling/algorithms, Statistical methods, Environment - enviromental exposure, pollution, Epigenetics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Physical - activity, fitness, function, Sleep, Statistical methods

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

B4113 - Exploring the epigenetic profiles of vapers smokers dual users abstainers and never users in ALSPAC - 20/09/2022

B number: 
B4113
Principal applicant name: 
Jasmine Khouja | University of Bristol (United Kingdom)
Co-applicants: 
Dr Rebecca Richmond, Prof Marcus Munafo, Dr Matthew Suderman, Dr Ryan Langdon, Alex Andrayas
Title of project: 
Exploring the epigenetic profiles of vapers, smokers, dual users, abstainers and never users in ALSPAC
Proposal summary: 

DNA methylation is an epigenetic change that can influence how our genes are expressed. Smoking has been found to influence DNA methylation, and these changes could be responsible for some of the negative health consequences of smoking. In comparison, the epigenetic changes associated with e-cigarette use are not well known. In this project, we will explore how e-cigarette use is associated with DNA methylation.

Impact of research: 
1. Publications and/or conference presentations that will further understanding of the epigenetic changes associated with e-cigarette use. 2. Findings for inclusion in future grant applications and possible publications.
Date proposal received: 
Wednesday, 20 July, 2022
Date proposal approved: 
Tuesday, 26 July, 2022
Keywords: 
Molecular genetics and genomics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Computer simulations/modelling/algorithms, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Epigenetics, Genetic epidemiology

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

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.

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

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