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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B4246 - The role of genetics in the intergenerational transmission of IPVA - 07/02/2023

B number: 
B4246
Principal applicant name: 
Emma Dennie | Bristol Medical School
Co-applicants: 
Dr. Hannah Sallis, Dr Marcus Munafo, Dr. Annie Herbert, Dr. Angela Attwood
Title of project: 
The role of genetics in the intergenerational transmission of IPVA
Proposal summary: 

Intimate Partner Violence and Abuse (IPVA; whether cohabiting or not) is a widespread public health issue which often results in serious physical and psychological harm. In the last 50 years, research has been dedicated to understanding IPVA, including its effects and why it takes place. Research has highlighted that individuals who experience or witness IPVA during childhood are more likely to become perpetrators or survivors of IPVA in the future which is referred to as intergenerational transmission. However, the mechanisms behind this are debated. There are several theories in the literature including Social Learning Theory and biological theory, which are among the more prominent. The social learning approach theorises that offspring learn the violent attitudes/behaviour from their environment, in particular their parent(s). However, this theory does not account for the offspring in violent homes who do not exhibit IPVA in their relationships, or those who do not grow up in violent homes who become perpetrators or survivors in the future. Recent findings suggest that IPVA is passed from parent to offspring through environmental factors, psychological factors, and underlying biological mechanisms including a genetic component. The studies on genetic liability and IPVA outcomes to date have largely involved twin studies with preliminary results. This study will expand on previous research and use a novel approach to explain why some offspring are at increased risk of perpetrating or suffering IPVA in their future relationships.

Impact of research: 
The research will be written up and submitted for publication to a peer reviewed journal. This research will provide a springboard for future genetic and epigenetic research on IPVA, in order to better understand mechanisms of intergenerational transmission of IPVA. It will inform future interventions for secondary prevention of offspring IPVA.
Date proposal received: 
Tuesday, 31 January, 2023
Date proposal approved: 
Tuesday, 7 February, 2023
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, GWAS, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Genetic epidemiology, Genome wide association study, Mendelian randomisation, Offspring

B4249 - Understanding causes and consequences of body composition cardiorespiratory and muscular fitness - 06/02/2023

B number: 
B4249
Principal applicant name: 
Snehal M Pinto Pereira | UCL (United Kingdom)
Co-applicants: 
Prof Mark Hamer, Prof Rachel Cooper, Prof Ulf Ekelund, Dr Alex Ireland, Prof Nicholas Timpson
Title of project: 
Understanding causes and consequences of body composition, cardiorespiratory and muscular fitness
Proposal summary: 

Health related physical fitness has 3 main subcomponents: body composition, cardiorespiratory fitness (CRF) and muscular fitness. Body composition refers to the percentage of muscle, fat, bone and water in the body; CRF refers to the ability of the heart and lungs to supply oxygen to muscles during physical activity; muscular fitness refers to the ability to do work against a load (and is usually judged by muscle strength). The 3 components of physical fitness are affected by physical activity and are associated with important health outcomes like cardiovascular disease and frailty. Body composition, CRF and muscular fitness develop and change over a lifetime, and, in adulthood, meaningful changes in them are achievable in the general population. Thus, if we want to develop strategies to maintain our health for as long as possible, we need to understand the causes and consequences of these 3 aspects of fitness as well as how they are related to each other.
Behaviours can influence the components of fitness, e.g., higher intensity physical activity is associated with subsequent higher CRF. So, it is unsurprising that government guidelines recommend doing activities to improve/maintain CRF (i.e., moderate-to-vigorous intensity activity) and muscle strength (i.e., strength building activities). However, the general population’s perception of physical activity is skewed towards aerobic activity which mostly benefits CRF. Muscle strengthening activities are often referred to as ‘forgotten’ guidelines. To demonstrate and emphasise the unique added value of the different types of physical activity recommended by the guidelines, we need to understand the independent effects of CRF and muscle strength on health. Moreover, the fitness components are interrelated and can influence each other, but questions remain unanswered, e.g., we do not know whether duration of exposure to obesity is important for CRF or the extent to which CRF influences muscle strength and vice-versa. Understanding interrelationships with obesity in particular is crucial, because, compared with older generations, younger generations are accumulating greater exposure to obesity throughout their lives, and the impact of living longer with obesity is potentially enormous.
‘Real life’ is complex and outside of a lab or a randomised trial it is difficult to assess cause. However, some extremely important health questions like ‘how much of the effect of obesity on poor health could be avoided if everyone was strong?’ cannot be answered in a lab or by doing a trial. This is where the approach we will adopt is valuable: we will use different analytical methods and different datasets to answer our questions. The datasets and methods we will use have different strengths and weaknesses and taken together they overcome weaknesses of studying cause and effect in a single dataset with a single method. Therefore, our adopted approach is extremely powerful in terms of triangulating evidence for (or against) causality when results from the different datasets and analysis methods are considered collectively. We will use the 5 different national cohorts to address 3 specific knowledge gaps. We aim to better understand the (i) interrelations between components of physical fitness (muscular fitness, CRF, and body composition), how they affect each other and subsequently cause poor health; and to improve understanding of influences over a life-time on, and the development of, (ii) CRF and (iii) muscular fitness. Our work will promote the physical activity guidelines regarding specificity of types of exercise that should be encouraged at the population level and provide evidence for when an ideal life stage might be to intervene to promote maintenance of high levels of CRF and muscular fitness for as long as possible. This work is therefore of relevance, and, will have impact on, health policy. Finally, our work will demonstrate how to make best use of existing data resources.

Impact of research: 
By addressing the 3 identified knowledge gaps I will advance not only academic research, but also deliver demonstrable value for health policy. For example, my work will promote CMO guidelines regarding specificity of types of exercise that should be encouraged at the population level and provide evidence for when an ideal life stage might be to intervene to promote maintenance of high levels of cardiorespiratory/muscular fitness for as long as possible.
Date proposal received: 
Monday, 6 February, 2023
Date proposal approved: 
Monday, 6 February, 2023
Keywords: 
Epidemiology, Obesity, physical activity, Computer simulations/modelling/algorithms, Statistical methods, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Mendelian randomisation, Physical - activity, fitness, function, Statistical methods

B4247 - Genetic Research Of Asthma From The Study Of Genes Belonging To Metabolic Pathways Including Interleukin 6 Search For Associati - 07/02/2023

B number: 
B4247
Principal applicant name: 
Raquel Granell | MRC IEU, Population Health Sciences, Bristol Medical School
Co-applicants: 
Dr Christina Dardani, Marie-Helene Dizier, Rachel Nadif, Laurent Orsi, Patricia Jeannin
Title of project: 
Genetic Research Of Asthma From The Study Of Genes Belonging To Metabolic Pathways Including Interleukin 6: Search For Associati
Proposal summary: 

Dysregulation of the immune defence system of the lungs can induce inflammation and lead to chronic respiratory diseases, such as chronic obstructive pulmonary disease or asthma. Numerous cytokines are involved in this process. Among these cytokines, those of the interleukin 6 (IL-6) family play a very important immunoregulatory role. Recent studies on IL-6 have shown that this cytokine is not simply a by-product of inflammation, but instead may play a role in the aetiology of asthma. It has been suggested that a deeper understanding of the molecular mechanisms and pathways related to IL-6 could improve asthma treatment while minimising side effects. A few genetic studies have already reported an association between IL-6 genetic variants and asthma, with divergent results depending on the type of asthma. Specifically, a Finnish study showed an association with adult-onset allergic asthma, while a GWAS study showed an association specifically with childhood-onset asthma and no association with adult-onset asthma. The association between IL-6 and asthma seems to be established, but not yet well understood, especially regarding to which asthma phenotype the cytokine may be related. Furthermore, interactions between IL-6 and tobacco smoking exposure were shown in different diseases including asthma.

Impact of research: 
Date proposal received: 
Thursday, 2 February, 2023
Date proposal approved: 
Monday, 6 February, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Allergy, GWAS, Genome wide association study

B4244 - Genetics of neurodevelopmental traits and disorders in ALSPAC - 15/05/2023

B number: 
B4244
Principal applicant name: 
Hilary Martin | Wellcome Sanger Institute, UK (UK)
Co-applicants: 
Dr. Varun Warrier, Prof. Stephan Sanders, Prof. Michael Talkowski, Dr. Mahmoud Koko Musa, Dr. Ruth Eberhardt, Dr. Kyle Satterstrom, Dr. Shan Dong, Dr. Jack Fu, Dr. Stephanie Hao, Yuanjun Gu
Title of project: 
Genetics of neurodevelopmental traits and disorders in ALSPAC
Proposal summary: 

This project will look at the genetic underpinnings of neurodevelopmental traits such as cognitive ability and social and communication difficulties, and the genetics of related conditions such as autism, intellectual disability and ADHD. It is known that both common and rare genetic variants influence these traits. In this project, we will use the extensive longitudinal data in ALSPAC to construct trajectories of neurodevelopmental traits over time, and look at genetic influences on these and whether they are moderated by environmental factors. We will also contribute data to the Autism Sequencing Consortium (ASC), a leading international collaborative group working on deciphering autism genetics and its relation to cognition and brain development. We plan to combine ALSPAC clinical and sequencing data with other datasets of similar nature from the ASC, to identify new genes underlying autism, understand genetic differences between autistic individuals who have different co-morbidities and understand sex differences in autism.

Impact of research: 
Our research will lead to a greater understanding of how different types of genetic and environmental factors affect neurodevelopment and its relation to autism. It will increase our understanding of the relationship between rare genetic variants and autistic traits, helping decipher the elusive mechanisms of observed sex differences in autism.
Date proposal received: 
Thursday, 26 January, 2023
Date proposal approved: 
Monday, 30 January, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Epilepsy, Learning difficulty, Mental health, Speech/language problem, DNA sequencing, GWAS, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Speech and language, Communication (including non-verbal), Development, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Neurology, Sex differences

B4244 - Genetics of neurodevelopmental traits and disorders in ALSPAC - 15/05/2023

B number: 
B4244
Principal applicant name: 
Hilary Martin | Wellcome Sanger Institute, UK (UK)
Co-applicants: 
Dr. Varun Warrier, Prof. Stephan Sanders, Prof. Michael Talkowski, Dr. Mahmoud Koko Musa, Dr. Ruth Eberhardt, Dr. Kyle Satterstrom, Dr. Shan Dong, Dr. Jack Fu, Dr. Stephanie Hao, Yuanjun Gu
Title of project: 
Genetics of neurodevelopmental traits and disorders in ALSPAC
Proposal summary: 

This project will look at the genetic underpinnings of neurodevelopmental traits such as cognitive ability and social and communication difficulties, and the genetics of related conditions such as autism, intellectual disability and ADHD. It is known that both common and rare genetic variants influence these traits. In this project, we will use the extensive longitudinal data in ALSPAC to construct trajectories of neurodevelopmental traits over time, and look at genetic influences on these and whether they are moderated by environmental factors. We will also contribute data to the Autism Sequencing Consortium (ASC), a leading international collaborative group working on deciphering autism genetics and its relation to cognition and brain development. We plan to combine ALSPAC clinical and sequencing data with other datasets of similar nature from the ASC, to identify new genes underlying autism, understand genetic differences between autistic individuals who have different co-morbidities and understand sex differences in autism.

Impact of research: 
Our research will lead to a greater understanding of how different types of genetic and environmental factors affect neurodevelopment and its relation to autism. It will increase our understanding of the relationship between rare genetic variants and autistic traits, helping decipher the elusive mechanisms of observed sex differences in autism.
Date proposal received: 
Thursday, 26 January, 2023
Date proposal approved: 
Monday, 30 January, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Epilepsy, Learning difficulty, Mental health, Speech/language problem, DNA sequencing, GWAS, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Speech and language, Communication (including non-verbal), Development, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Neurology, Sex differences

B4240 - Migraine and inflammation during pregnancy and ADHD in the offspring- Disentangling the causal links - 30/01/2023

B number: 
B4240
Principal applicant name: 
Evie Stergiakouli | MRC IEU
Co-applicants: 
Miss Yaxin Luo, Dr Christina Dardani, Dr Rachel Blakey
Title of project: 
Migraine and inflammation during pregnancy and ADHD in the offspring- Disentangling the causal links
Proposal summary: 

Attention Deficit Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental condition (Rube & Kaur, 2012) that has been associated with several adverse health outcomes. Some of them are auto-immune conditions and migraine. However, the mechanisms behind these associations are unclear and it remains to be established if maternal immune-related conditions and migraine during pregnancy could increase risk for ADHD in the offspring.
Studies have suggested that the prevalence of ADHD is significantly higher in children with migraine (Arruda et al., 2010), although they are different kinds of brain disorders(Justyna, 2017). Migraine is twice as prevalent in females, and acetaminophen (paracetamol), a common medication indicated for migraine, is considered generally safe for use during all stages of pregnancy. However, there is evidence indicating that acetaminophen use during the prenatal period may increase the risk of multiple behavioural difficulties in the offspring (Stergiakouli et al., 2016). The mechanisms for the association remain unclear. One hypothesis is that migraine and ADHD may share common genetic variants. Meanwhile, paracetamol could be mediating the association between migraine and ADHD. Distinguishing between these explanations is important because they have different prevention and treatment implications.
Research suggests that ADHD and immune-related conditions might co-occur (Anand et al., 2017). Although associations exist between ADHD and asthma (Leffa et al., 2021), little is known about the potential role of ADHD in later inflammation. We hypothesize that ADHD might be involved in the pathway of development of inflammation or immunological indicators. Further study is warranted to assess the causal association between ADHD and inflammation indicators in different stages in the lifespan.

Impact of research: 
We hope to develop a better understanding of the offspring health effects of mothers with migraine and migraine related medicine during pregnancy. Meanwhile, we hope to better understand the origins and consequences of ADHD.
Date proposal received: 
Friday, 20 January, 2023
Date proposal approved: 
Monday, 30 January, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Microarrays, NMR, Statistical methods, Genetic epidemiology, Genetics, Mothers - maternal age, menopause, obstetrics, Offspring

B4242 - Children of the 90s Coping strategies Study Long COVID sub-study - 30/01/2023

B number: 
B4242
Principal applicant name: 
Jean Golding | University of Bristol (United Kingdom)
Co-applicants: 
Prof Carol Joinson, Mrs Yasmin Iles-Caven, Prof Kate Northstone, Prof Crystal Park, Dr Lucy Beasant
Title of project: 
Children of the 90s Coping strategies Study (Long COVID sub-study)
Proposal summary: 

Children of the 90s aims to discover as much as possible about our health. People cope in many different ways with ill health, especially long-term or chronic illnesses. By interviewing 120 Children of the 90s participants with either long Covid, diabetes or asthma, we hope to gain important insights into the most effective ways of managing chronic conditions.

Impact of research: 
The interviews proposed in this study are part of a much larger study investigating a number of major research questions concerning beliefs and behaviours, including religiosity and spirituality and their relationship with health and well-being (see https://ahrp.blogs.bristol.ac.uk/) Findings from the Beliefs, Behaviours & Health Research Programme (RSBB) will be used to inform the academic community and the public of any advantages (or disadvantages) of religious/spiritual beliefs and behaviours to health.
Date proposal received: 
Thursday, 26 January, 2023
Date proposal approved: 
Monday, 30 January, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, long COVID, Qualitative study, long COVID, coping, beliefs, behaviours

B4181 - Movement behaviours cardiometabolic risk and body composition in children and adolescents - 06/03/2023

B number: 
B4181
Principal applicant name: 
Youngwon Kim | The University of Hong Kong (China)
Co-applicants: 
Dr. Au Yeung Shiu Lun Ryan
Title of project: 
Movement behaviours, cardiometabolic risk, and body composition in children and adolescents
Proposal summary: 

Objectives: To investigate the associations of lifestyle behaviours with indicators of cardiometabolic health and body composition and whether the associations vary by genetic susceptibility in children and adolescents.

Methods: We will use both genotype and phenotype data from the “Avon Longitudinal Study of Parents and Children” birth cohort of European children and adolescents. Genetic risk for unhealthy levels of cardiometabolic risk markers and body composition will be calculated based on the established trait-specific genetic variants. We will use accelerometer data (collected at average ages 11, 13, 15 and 24 years) to derive sedentary time, light physical activity (PA) and moderate-to-vigorous PA, and 4 sets of questionnaire data to quantify 3 sedentary activities and 1 PA type.

Conclusions: Findings from the proposed research will indicate the roles of PA and sedentary time in enhancing cardiometabolic health and body composition, and whether such roles differ by genetic susceptibility in children and adolescents of European ancestry.

Impact of research: 
The evidence obtained from this project has the potential to motivate children and adolescents to adopt and sustain less sedentary and more physically active lifestyles which could help improve their cardiometabolic and body composition profiles. Our study findings will be highly translational given that our project has much potential to inform future lifestyle-modification intervention studies of children and adolescents, specifically those at high genetic risk of common chronic diseases.
Date proposal received: 
Sunday, 22 January, 2023
Date proposal approved: 
Thursday, 26 January, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Bone disorders - arthritis, osteoporosis, Obesity, GWAS, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Blood pressure, BMI, Cardiovascular, Genetic epidemiology, Physical - activity, fitness, function

B4234 - Investigating Associations Between Religious/Spiritual Beliefs and Behaviours and Inflammation - 06/02/2023

B number: 
B4234
Principal applicant name: 
Neil Goulding | Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol (United Kingdom)
Co-applicants: 
Dr Matthew Suderman
Title of project: 
Investigating Associations Between Religious/Spiritual Beliefs and Behaviours and Inflammation
Proposal summary: 

This project will investigate whether someone’s religious/spiritual beliefs and behaviors (RSBB) influences protein levels of individuals and their offspring. It will be hypothesis driven, so we will look at all relevant RSBB-linked questions from ALSPAC questionnaires as possible exposures. We will also investigate whether attending a faith school (G1) is associated with protein levels at age 9 and 24. Furthermore, we will also explore whether intergenerational shifts in terms of people gaining/losing faith in ALSPAC have any effect on protein levels; and similarly, whether discordance between parents’ RSBB affects offspring protein levels.
The outcomes are the 92 proteins analysed by Olink, plus the inflammatory biomarkers Glycoprotein acetyls (GlycA) and C-reactive protein (CRP) which were measured previously in ALSPAC. We will also look at the ratio of IL-10 to IL-6, since it has been highlighted as an inflammation biomarker connected with spiritual activation. As a validation exercise, we will also include IL-6 measured by clinical chemistry, to compare with results from IL-6 measured by Olink. The ALSPAC proteomic data includes approximately 3000 samples from each of three age groups: the mothers from the 1st Focus on Mothers clinic (FOM1) and the children at ages 9 and 24, with a significant sample overlap between the three groups.

Impact of research: 
Identification of proteomic biomarkers of RSBB
Date proposal received: 
Thursday, 12 January, 2023
Date proposal approved: 
Thursday, 26 January, 2023
Keywords: 
Anthropology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Religiosity Spiritualism, Proteomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Statistical methods, Religion Spiritualism Proteomics

B4243 - Investigating the rise of liver disease in young adults in the UK - 01/03/2023

B number: 
B4243
Principal applicant name: 
Kushala Abeysekera | Population Heatlh Sciences (United Kingdom)
Co-applicants: 
Matthew Hickman, Nic Timpson , William Alazawi
Title of project: 
Investigating the rise of liver disease in young adults in the UK:
Proposal summary: 

90% of liver disease is potentially preventable with the main causes in the UK being damage from alcohol and obesity. Advanced liver disease rarely causes symptoms until very late. Sadly, liver disease is now one of the leading causes of death in 35-49 year olds. However, not all people who drink too much alcohol or have obesity will get liver disease early. Our study seeks to understand why some adults are developing liver disease earlier. By understanding who is developing liver disease early, and why, we can inform public health strategies, and target people most in need of support.

Whilst it can take many years to develop advanced liver disease, this provides an opportunity. Detecting liver disease early, in the community, can allow healthcare professionals to provide lifestyle advice, medication and surveillance to reduce the chance of patients developing complications of liver disease.

Impact of research: 
We have a unique time-sensitive opportunity here to prospectively map the development of steatosis and fibrosis in young adults in the general population setting, nested within ALSPAC. Determining the prevalence of liver fibrosis will provide much needed normative data and help hepatologists understand the burden of this clinically relevant disease in this poorly phenotyped age group. By understanding the causal risk factors leading to the progression of fibrosis in young adults, it can inform prevention and precision public health policy to mitigate risk factors and target pathways to disease, including potentially screening targeted groups earlier than is currently advised. Furthermore, as antifibrotic drugs and those that reverse non-alcoholic steatohepatitis are developed, this study offers a window into a new potential target population. Previous public involvement and patient support work done with ALSPAC participants and liver disease patients (through the British Liver Trust) has reiterated the importance of work such as this. Ultimately, our aim is to reveal the true burden of liver disease in young adults and determine how we can identify young adults with reversible liver fibrosis who can benefit from early intervention, to prevent progression to cirrhosis and support patients. Regarding outputs, we anticipate at least 3 peer-reviewed publications, multiple international conference presentations, support and development for one doctoral researcher, and invaluable experience for myself in leading the scientific direction of important new data, which would aid in developing their fellowship and lectureship bids. This Rosetrees Trust intermediate project grant would provide the resources needed to gather vital new data and enable a new generation of investigators to lead the advancement of liver disease epidemiology.
Date proposal received: 
Wednesday, 25 January, 2023
Date proposal approved: 
Wednesday, 25 January, 2023
Keywords: 
Epidemiology, Gastrointestinal, BMI

B4241 - Oestrogen as a protective factor for psychosis - 06/02/2023

B number: 
B4241
Principal applicant name: 
Sarah Sullivan | University of Bristol (England)
Co-applicants: 
Prof Carol Joinson, Prof Abigail Fraser, Prof Martha Hickey, Prof Stan Zammit, Prof Golam Khandaker, Dr Helen Bould
Title of project: 
Oestrogen as a protective factor for psychosis
Proposal summary: 

Psychosis is a severe mental illness. An example is schizophrenia. Symptoms of psychosis can include hearing voices and having strange and fixed ideas. It is not rare. Each person has a three in one hundred chance of developing psychosis over their lifetime. Psychosis has a very destructive effect on people's lives because the first episode often happens during late teens or early adulthood, at a time when people are finishing education or starting careers and forming long-term meaningful relationships. Psychosis can interrupt these important processes making it difficult for sufferers to catch up with the progress of their peers. It is also extremely expensive for the NHS to treat because it often requires lifetime medication and periods in psychiatric hospital. A recent study in England reported annual costs of £2 billion. Unfortunately, the outcomes for people with psychosis are often poor. About 25% of people relapse within 3 years of recovery, are likely to be unemployed long-term and have a poor quality of life. Relapses are very distressing for the patient and their family and increase treatment costs for the NHS.

Men have a higher risk of psychosis than women when young, but women are more at risk in later middle age. It has been suggested that this might be because a female sex hormone called oestrogen, protects women from psychosis from when they start their periods (when oestrogen levels rise) until the menopause (when oestrogen levels drop). Currently, there is not enough good quality evidence to know if this is correct. It is very important to find out whether this is true because an understanding of the underlying causes of a new episode of psychosis will help us to predict who is most risk and get them the help they need as soon as possible. This will, in turn, improve outcomes by reducing the
chance of a relapse and therefore reduce treatment costs for the NHS. I will use data from population-based long-term studies to see whether the age at which women start their periods, or experience menopause, is associated with risk of psychosis. If the oestrogen theory is correct, a later age of starting periods and an earlier age of experiencing the menopause will be linked to increased risk of psychosis. I will also use NHS prescription data to see if taking hormonal contraceptives and hormone replacement therapy, affect psychosis risk. Both these medications contain either oestrogen, or progesterone (another important female sex hormone) or both. Therefore, if the oestrogen theory is correct,
they may reduce the risk of psychosis. We will also be able to find out if progesterone has a role in risk of psychosis. This study proposes a new way to investigate this question using population-based data linked to NHS data.

Population data and NHS data are useful to researchers because they contain very large numbers of participants but there are also problems such as missing data and inaccurate recording, which can make the findings difficult to understand. To strengthen our findings in population data, we will also use genetic data which contains information about individual risk of psychosis and a woman's reproductive stage in life. These data have smaller numbers of participants than the population data and NHS data, but they do not have the same problems with missing data or inaccurate recording. Therefore, if we can find the same result in both types of data, we can be more confident that lower levels of oestrogen increase psychosis risk. We will also use population data from Sweden to find out whether the findings are the same outside the UK. The findings from this work will help doctors to identify women at greater risk of psychosis much earlier than happens now and provide opportunities for offering treatments that might prevent psychosis developing, like psychological or hormone-based drug therapies.

Impact of research: 
If oestrogen is protective for risk of psychosis, oestrogen levels could be one of the multiple factors that predict risk in older women.
Date proposal received: 
Tuesday, 24 January, 2023
Date proposal approved: 
Wednesday, 25 January, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, GWAS, Linkage, Liver function, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics

B4238 - Childhood socioeconomic position and adolescent mental health Inter-generational comparisons using data from three British birt - 23/01/2023

B number: 
B4238
Principal applicant name: 
Eoin McElroy | Ulster University (Northern Ireland)
Co-applicants: 
Caitlyn Rawers, Dr Orla McBride, Professor Jamie Murphy
Title of project: 
Childhood socioeconomic position and adolescent mental health: Inter-generational comparisons using data from three British birt
Proposal summary: 

Research strongly suggests that low socioeconomic position [SEP] in childhood is related to poorer mental health and behavioural outcomes, particularly in childhood and adolescence. Evidence suggests that low SEP is related to internalising and externalising symptoms, antisocial behaviour, and substance use behaviours. Interestingly, recent studies suggest that the relationship between childhood SEP and these emotional and behavioural outcomes are changing across generations.

Yet, these relationships vary considerably when different SEP indicators are examined. Traditional SEP indicators include income, education, occupational social class, and/or housing tenure; however, SEP is a multi-dimensional construct that is related to an individual's access to material, educational, and social resources. SEP indicators are limited in their ability to capture the multi-dimensionality of SEP when used in isolation, but using multiple SEP indicators can cause issues for statistical analysis if used improperly. Researchers have demonstrated that regression-based models may be inappropriate for investigating the effect of SEP on an outcome. Therefore, alternative approaches are needed and person-centred approaches, such as latent class analysis, are favoured in the literature.

Additionally, cross-cohort comparisons of emotional and behavioural outcomes necessitates retrospective harmonisation for the scales used. Retrospective harmonisation allows researchers to compare different scale measures that measure the same underlying construct in different cohorts, for example. Without conducting retrospective harmonisation, researchers cannot be assured that the findings observed not due to systematic differences between cohorts. This project will utilise both statistical processes to analyse differences in emotional and behavioural outcomes across three British birth cohorts.

Impact of research: 
This project will use retrospective harmonisation for measures of internalising and externalising behaviour, antisocial behaviour, and substance use to conduct valid cross-cohort comparisons on these constructs. Retrospective harmonisation has rarely used for cross-cohort comparisons in this field previously. Additionally, previous research has primarily focused on specific indicators of SEP instead of capturing multi-dimensional experiences of socioeconomic advantage and disadvantage, which this project will address using person-centred approaches. The effect of socioeconomic disadvantage on adolescent and adulthood outcomes is a significant area of concern due to the numerous and cumulative effects of early life adversity; the findings of this project may have significant implications for public policy and social welfare. It is anticipated that the results of this project will consolidate heterogenous findings on relationships between low childhood SEP and mental health, offending, and substance use in adolescence.
Date proposal received: 
Friday, 20 January, 2023
Date proposal approved: 
Monday, 23 January, 2023
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, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods

B4239 - Scarlet Fever in ALSPAC - 30/01/2023

B number: 
B4239
Principal applicant name: 
Nic Timpson | MRC-IEU (United Kingdom)
Co-applicants: 
Fergus Hamilton
Title of project: 
Scarlet Fever in ALSPAC
Proposal summary: 

Streptococcal infection is common, but occasionally serious. In the winter of 2022, a large increase in severe streptococcal infection due to invasive Group A Streptococcus (also known as S.pyogenes) was identified in the U.K. and elsewhere in Europe, leading to a number of childhood deaths. The human genetic determinants of streptococcal infection are as yet largely unknown, with previous research only identifying associations at one area of the genome (the Human Leukocyte Antigen region). In this project, we want to perform a genome wide association study of Scarlet Fever, a form of infection caused by Group A streptococci. There are approximately 150 cases of self-reported Scarlet Fever in ALSPAC. The summary statistics from this GWAS (not the raw data) will be shared and meta-analysed with other GWAS of scarlet fever (e.g. UK Biobank, 23andMe), in order to help develop an understanding of the determinants of invasive group A streptococcus. This research is a priority for the UK Health Security agency.

Impact of research: 
This will help increase our understanding of streptococcal infection and understand why some people get invasive disease and others do not. Streptococcal infection remains a major health problem in both developing and developed countries.
Date proposal received: 
Friday, 20 January, 2023
Date proposal approved: 
Monday, 23 January, 2023
Keywords: 
Immunology, Infection, GWAS, Genetics, Genomics, Genome wide association study

B4237 - Intergenerational effects of perinatal intimate partner violence Longitudinal study of neurodevelopmental outcomes in childhood - 06/02/2023

B number: 
B4237
Principal applicant name: 
Aja Murray | University of Edinburgh (United Kingdom)
Co-applicants: 
Mrs Juweria Baig
Title of project: 
Intergenerational effects of perinatal intimate partner violence: Longitudinal study of neurodevelopmental outcomes in childhood
Proposal summary: 

Researchers suspect that children born to mothers who were abused by their partner during pregnancy are disadvantaged in terms of their development. They are more likely to experience mental health and cognitive problems over their life and an increased risk of neuro-developmental problems like Attention deficit hyperactivity disorder, Autism Spectrum Disorder, and Dyspraxia. In order to design effective interventions to help children whose mothers were abused while pregnant with them, it is essential for us to understand the pathways that link abuse during pregnancy to child outcomes. ALSPAC has the data needed to understand these kinds of pathways. Our project seeks to use the data to test which pathways are most important, helping us to understand the kind of support that abused mothers need to minimise the long-term effects of abuse on their child.

Impact of research: 
We anticipate that our results will address gap in the existing literature to address the pathways of intimate partner violence during pregnancy which lead to neuro developmental problems. Current interventions primarily seek to reduce IPV and to improve maternal outcomes. They have the potential to expand their scope to address effects on children prenatally exposed to IPV; however, there is currently a paucity of evidence on which to base such extensions.
Date proposal received: 
Wednesday, 18 January, 2023
Date proposal approved: 
Thursday, 19 January, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Learning difficulty, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function

B4236 - The association between early childhood dietary variety score with nutrient profiles and later dietary pattern scores - 16/01/2023

B number: 
B4236
Principal applicant name: 
Kate Northstone | UoB (United Kingdom)
Co-applicants: 
Louise Jones, Bethany Winstone
Title of project: 
The association between early childhood dietary variety score with nutrient profiles and later dietary pattern scores
Proposal summary: 

A healthy diet in childhood is really important for growth and development. Habits formed in childhood can persit into adulthood. It has been shown that variety in the diet (i.e. the different types of foods consumed) is relatively low at 2 years of age but increases by the age of 4.

These changes could be due to lots of factors such as environmental and social aspects of a child’s upbringing. For example, low socioeconomic status of the mother is associated with a low dietary variety score, whilst a higher dietary variety score is associated with children being less picky with their food choices.

A healthy diet consists of a variety of fruit and vegetable sources, carbohydrates, and low saturated fat, sugar and salt consumption.Vitamin D is a necessary vitamin needed for bone strength and development, however low levels in childhood is a common issue within the UK.

This project will look to see how dietary variety in childhood is associated with nutrient intakes (saturated fat, salt, sugar, fibre and vitamin D). It will also see whether dietary variety is associated with dietary pattern scores that have been created at age 7 (dietary patterns are healthy, processed).

Impact of research: 
Understanding whether a varied diet in early childhood leads to an improved nutrient profile will contribute to public health messaging
Date proposal received: 
Saturday, 14 January, 2023
Date proposal approved: 
Monday, 16 January, 2023
Keywords: 
Epidemiology, Nutrition - breast feeding, diet

B4235 - The association between academic pressure and adolescent depression and self-harm - 27/02/2023

B number: 
B4235
Principal applicant name: 
Gemma Lewis | University College London (United Kingdom)
Co-applicants: 
Marie Mueller
Title of project: 
The association between academic pressure and adolescent depression and self-harm
Proposal summary: 

Academic Pressure can be defined as fear of failure, concerns about the future, stress about workload and exams, worries about parental expectations, and competition with peers for grades. The UK has some of the highest levels of academic pressure in secondary schools, and this has risen in recent decades. Despite widespread concerns about academic pressure in the UK, it has rarely been investigated in relation to adolescent mental health.

My project will investigate whether academic pressure is a modifiable causal risk factor for adolescent depression, self-harm and suicide. If so, academic pressure could be targeted in universal interventions in schools, to prevent adolescent depression, self-harm and suicide.

Impact of research: 
My work with young people and teachers suggests that academic pressure is influenced by individuals, schools, families, policy, and society. My research could therefore inform prevention at each of these levels. I am particularly interested in the possibility of whole-school interventions
Date proposal received: 
Friday, 13 January, 2023
Date proposal approved: 
Monday, 16 January, 2023
Keywords: 
Epidemiology, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B4233 - Investigate maternal and paternal risk factors for violence during pregnancy and its lasting impact for everyone - 11/01/2023

B number: 
B4233
Principal applicant name: 
Heidi Stöckl | Ludwig-Maximilians-University Munich (Germany)
Co-applicants: 
Sarah Meyer, Neema Mosha, Rebecca Brambilla
Title of project: 
Investigate maternal and paternal risk factors for violence during pregnancy and its lasting impact for everyone
Proposal summary: 

Intimate partner violence is a recognized human rights, development, and public health issue, with one in three women globally estimated to have experienced physical and/or sexual violence by their partner during their lifetime. One of the times in life when women are believed to be spared from violence is pregnancy, a period when the well-being of the women and their unborn children is often prioritized. Yet, the reality is different. Worldwide, the prevalence of physical intimate partner violence during pregnancy ranges from 1 to 28 percent, with one in four women reporting that the violence was explicitly directed at their pregnant abdomen. The overarching aim of this proposal is to understand the risk and protective factors to mitigate the intergenerational transmission of violence during pregnancy and its short and long-term effects of violence during pregnancy. This will be achieved by firstly investigating the short and long-term social and health effects of violence during pregnancy on women and on their male and female children, secondly establishing that violence during pregnancy is a marker for severe violence during the lifetime and thirdly, exploring the maternal and paternal risk and protective factors for the intergenerational transmission of violence during pregnancy. Information on short and long-term health consequences will be based on both biomarkers and self-reported health assessments of mothers, daughters and sons.

Impact of research: 
Data emerging from this analysis will be synthesized with data emerging from a parallel cohort that we are aiming to collect data from in Bangladesh (MINIMAT birth cohort), cross-sectional data analysis using the Demographic and Health Surveys and qualitative interviews. Together, this information that provides evidence that emerging pathways and mechanisms are not only relevant for one part of the world should inform the development of an ecological intergenerational theoretical framework to inform programmes that prevent violence during pregnancy early on, influence other violence prevention programmes and promote the most effective multi-sectoral provisions and strategies for intervention.
Date proposal received: 
Wednesday, 11 January, 2023
Date proposal approved: 
Wednesday, 11 January, 2023
Keywords: 
Social Science, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Intimate partner violence, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Fathers, Mothers - maternal age, menopause, obstetrics, Offspring, Social science

B4232 - Investigating life-course effects of adiposity on inflammation - 11/01/2023

B number: 
B4232
Principal applicant name: 
Lucy Goudswaard | Population Health Sciences, University of Bristol (United Kingdom)
Co-applicants: 
Professor Nicholas Timpson, Dr Laura Corbin, Dr David Hughes
Title of project: 
Investigating life-course effects of adiposity on inflammation
Proposal summary: 

Obesity (body mass index (BMI) of >30 kg/m2) is associated with low-grade chronic inflammation. Studies which have used a technique called Mendelian randomization (MR) have demonstrated that the relationship between body mass index and inflammatory proteins is causal. However, the timing of the onset of this inflammation is unclear. Inflammation could be a phenomenon which starts later in life as a result of a sustained high BMI over the life-course. Alternatively, it could be that a high BMI causes inflammation even in young children. Understanding the timing of this relationship is an important public health question as it could help in understanding the health impact of overweight/obesity in early life.

Impact of research: 
This work will help with understanding the effect of overweight/obesity in early life.
Date proposal received: 
Tuesday, 10 January, 2023
Date proposal approved: 
Wednesday, 11 January, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Obesity, Proteomics, Mendelian randomisation

B4231 - Psychological and neural correlates of excessive rationalisation in obsessive-compulsive disorder - 16/01/2023

B number: 
B4231
Principal applicant name: 
Elizabeth Kirkham | University of Edinburgh (Scotland, UK)
Co-applicants: 
Dr Heather Whalley
Title of project: 
Psychological and neural correlates of excessive rationalisation in obsessive-compulsive disorder
Proposal summary: 

Obsessive-compulsive disorder (OCD) is common and often debilitating, yet it remains under-researched and poorly
understood. OCD usually develops during childhood or adolescence, often amidst stressful environments. This raises the
possibility that OCD emerges as a psychological strategy aimed at reducing the anxiety caused by unavoidable stressful
situations (such as domestic violence). I term this strategy “excessive rationalisation”. Neurologically, excessive
rationalisation might be related to prefrontal “control” brain regions trying too hard to calm down “anxious” limbic regions.
Previous research suggests that people who show these patterns of brain activity may get less benefit from OCD
treatment. Therefore improved understanding of these patterns of brain activity and related psychological mechanisms
could help the 30-40% of people whose OCD doesn’t respond to treatment. This project will therefore investigate the novel
concept of excessive rationalisation and how it relates to brain activity in people with OCD.

Growing up with OCD has given me a passion to advance our scientific understanding of this debilitating condition. The
initial idea for this research came from my perspective as a person with OCD. I then drew on my expertise in mental health
and neuroscience to translate the idea into a research proposal, and showed it to three external advisors who also have
OCD. They wrote that focusing on early life stress and treatment-resistance is a “really important” endeavour which could
plug a significant gap in our understanding and treatment of OCD. After reading the proposal one person wrote, “this
research gives people like me some hope.”

Impact of research: 
My research will likely lead to new ways of understanding OCD, a mental health condition which is common and highly disabling, yet chronically under-researched. Given the lack of existing research which takes either a longitudinal or neuroscientific approach to OCD, any findings from this project are likely to "punch above their weight" in terms of impact in the mental health research sphere. In addition, I am hoping that successful research using ALSPAC will help me make a stronger case for inclusion of OCD measures in other imaging cohorts, such as UK Biobank.
Date proposal received: 
Thursday, 22 December, 2022
Date proposal approved: 
Wednesday, 4 January, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Medical imaging, Qualitative study, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Equipment - MRI, Environment - enviromental exposure, pollution, Neurology, Psychology - personality, Social science

B4230 - Early detection causes and consequences of sleep apnea - 30/01/2023

B number: 
B4230
Principal applicant name: 
Sarah J Lewis | Population Health Sciences, IEU (United Kingdom)
Co-applicants: 
Dr Peter Claes, Dr Sarah Baumeister, Dr Ulrich Bartsch, Kate Northstone, Professor Nic Timpson, Professor Stephen Richmond
Title of project: 
Early detection, causes and consequences of sleep apnea
Proposal summary: 

Sleep apnea is a condition characterised by interrupted breathing during sleep. People with sleep apnea have multiple extended pauses in breath when they sleep. The symptoms of sleep apnoea include loud snoring, gasping during sleep, unrefreshing sleep, and excessive daytime sleepiness. Sleep apnea is a common condition and occurs in around 25% among 30-69 year olds and increases with age. Worldwide it is estimated that between 711 million and 961 million adults are affected by the condition. Although common sleep apnea is largely undiagnosed, which is a problem because untreated sleep apnea may result in other health conditions, including high blood pressure, increased risk of stroke or coronary heart disease, increased risk of a serious accident caused by tiredness and depression or other mental health problems. The economic and societal burden of obstructive sleep apnoea is substantial, accounting for billions of pounds worldwide per year. A health economics report conducted for the British Lung Foundation estimated that investing in more awareness, diagnosis and treatment of sleep apnea could save the NHS £28 million per year and prevent up to 40,000 road traffic accidents.
Diagnosis of sleep apnea is largely based on identifying those at high risk followed by home monitoring using portable devices. There is uncertainty about the accuracy of current diagnostic tools and there is the potential to improve on identifying those at high risk by incorporating features of the brain and face structure into risk prediction models.
Several potential risk factors for sleep apnea have been identified, many of which could either be avoided or treated to improve symptoms if found to be causal. These include obesity, alcohol intake, cigarette smoking, use of sedatives, hormonal anomalies, nasal congestion, sleeping lying on the back and genetics. In addition, it is currently unclear whether treatment for sleep apnea improves related health outcomes. This will depend on whether sleep apnea causes these outcomes or whether pre-existing health outcomes lead to sleep apnea.
We plan to make use of a wealth of imaging, genetic and self-reported questionnaire data already collected in UKBiobank, ALSPAC and other large cohort studies and to collect new data in ALSPAC to determine which factors can be used to improve risk prediction models for sleep apnea, to identify modifiable risk factors for sleep apnea and to determine which health outcomes arise as a result of untreated sleep apnea.

Impact of research: 
Findings from this study will be used to prevent and treat sleep apnea to reduce the prevalence and associated co-morbidities.
Date proposal received: 
Wednesday, 21 December, 2022
Date proposal approved: 
Wednesday, 4 January, 2023
Keywords: 
Epidemiology, Sleep apnea, Medical imaging, Face - face shape, Genetic epidemiology, Growth, Mendelian randomisation, Sleep

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