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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B4070 - Rapid evaluation of interventions for close contact infectious diseases - 31/05/2022

B number: 
B4070
Principal applicant name: 
Ellen Brooks Pollock | University of Bristol (United Kingdom)
Co-applicants: 
Dr Leon Danon, Dr Amy Thomas, Dr Emily Nixon, Prof Nicholas Timpson, Dr Kate Northstone
Title of project: 
Rapid evaluation of interventions for close contact infectious diseases
Proposal summary: 

During the COVID-19 pandemic, ALSPAC ran a rapid survey of risk mitigation behaviours. We used the data to inform a transmission model of the SARS-CoV-2 Omicron-variant wave. We would like to develop the methods we started during the COVID-19 pandemic to create a public health decision-making tool. We propose to work with the ALSPAC cohort to characterise infection prevention practices and to understand the trade-offs between measures.

Impact of research: 
We are developing a tool for public health decision makers to use. The impact will be an increased evidence-base for public health decisions.
Date proposal received: 
Tuesday, 17 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Infection, Mathematical/infectious disease modelling, Infectious diseases

B4071 - Childhood adversity DNA methylation risk scores and risk for depression across development - 20/05/2022

B number: 
B4071
Principal applicant name: 
Alexandre Lussier | Massachusetts General Hospital (United States)
Co-applicants: 
Dr. Erin C. Dunn
Title of project: 
Childhood adversity, DNA methylation risk scores, and risk for depression across development
Proposal summary: 

Childhood adversity (e.g., abuse or maltreatment, family disruption or dysfunction, poverty, etc.) is one of the most potent life experiences linked to depression, nearly doubling the risk for a first onset. Emerging evidence also suggests that the effects of adversity on depression may vary based on when in the lifespan it occurs. In other words, there may be sensitive periods when the brain is “plastic” and experiences can impart more enduring effects field. However, the biological mechanisms linking childhood adversity to long-term vulnerability for depression remain poorly understood. One possibility is that adversity reprograms the epigenome through DNA methylation (DNAm), epigenetic modifications that do not change the sequence of the genome, but can alter gene expression. Recent evidence also suggests that DNAm risk scores (MRS) generated from large-scale studies of early-life exposures and/or mental outcomes may help predict and interpret risk for depression and other mental disorders.

To this end, we recently completed the largest analysis of time-varying childhood adversity and genome-wide DNAm in childhood, analyzing the impact of five types of adversity across seven longitudinal birth cohorts (N=2,347-3,279). Through these analyses, we identified distinct epigenetic signatures for five types of childhood adversity, as well as further evidence of sensitive periods for the effects of adversity on DNAm. However, it remains unknown whether DNAm risk scores generated from these data can accurately explain and predict depression risk across development.

As such, we seek to extend this research, which included data from the ALSPAC cohort, to further investigate the relationship between childhood adversity, DNAm, and depressive symptom trajectories across development. The central hypothesis we will test is that DNA methylation patterns linked to childhood adversity can be used as predictors of both prior exposures to adversity and future depressive outcomes, with measurable effects on depressive symptom trajectories.

Impact of research: 
By testing our central hypothesis, we will determine whether composite measures of childhood adversity can be identified through epigenetic alterations and whether these biological measures can predict the onset and severity of psychopathology. As the first longitudinal investigation of DNA methylation risk scores for childhood adversity and depression, this research the stage for a broader research program aimed at determining how epigenetic mechanisms can be used to predict and interpret risk for mental illness across the life course. Importantly, this work will help identify the molecular mechanisms that drive risk for depression across development, as well as delineate the periods when childhood adversity and DNA methylation have greater effects on depression risk, which will help guide optimally-timed interventions to reduce the burden of depression. Such efforts will help target prevention and treatment efforts to people who are at higher risk for mental illness and ultimately, will help improve the overall well-being of youth and adults affected by depression.
Date proposal received: 
Friday, 13 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Computer simulations/modelling/algorithms, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Epigenetics, Genetics

B4069 - Autistic traits anxiety and eating behaviours Longitudinal trajectories across child development - 20/05/2022

B number: 
B4069
Principal applicant name: 
Moritz Herle | Kings College London (United Kingdom)
Co-applicants: 
Dr Helena Zavos , Dr Virginia Carter Leno
Title of project: 
Autistic traits, anxiety, and eating behaviours: Longitudinal trajectories across child development
Proposal summary: 

Recent empirical work suggests the prevalence of eating disorders may be raised in autistic individuals, however, questions remain as to whether the co-occurrence of autism and eating disorders could be due to selective samples and/or difficulties disentangling symptoms of autism as compared to symptoms of eating disorders. An alternative explanation is that autism, or high levels of autistic traits, in childhood, may causally increases risk for eating disorders later in development. In addition, autistic children often experience high level of anxiety, and might use overeating or binge eaitng as a coping strategy to sooth and calm themselves down, which might put them on increased risk for later eating disorders. Further research into the pathways and potential mediators of the link between autism, anxiety,and eating disorders is needed to illuminate underpinning mechanisms, which in turn will highlight targets for prevention/intervention.

Impact of research: 
Date proposal received: 
Friday, 20 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Eating disorders - anorexia, bulimia, Mental health, Statistical methods, Statistical methods

B4065 - The Impact of Early Child Development on Social Mobility in the UK - 13/06/2022

B number: 
B4065
Principal applicant name: 
Matt Dickson | University of Bath (United Kingdom)
Co-applicants: 
Mrs Rachel Ambler
Title of project: 
The Impact of Early Child Development on Social Mobility in the UK
Proposal summary: 

The main research question that this project will address is: how do parental investments and parenting practices in the pre-school years influence the formation of human capital in children and contribute to the transmission of socio-economic status between generations.

During the pre-school years, though there are many outside influences on children, it is parents that have the greatest impact on their offspring. Parental investments before the age of three are likely to be as important, if not more, than what happens from age three onwards, given the dynamic complementarity between early and later skill development.

The project aims to extend our understanding of how (and when) gaps in attainment across socio-economic status emerge. We will map the relationships between measures of parental investment in the early years and long-term socio-economic outcomes and investigate the extent to which these are mediated through educational attainment. The empirical analysis will use data from the Avon Longitudinal Study of Parents and Children (ALSPAC) with linkage to the National Pupil Database. The data will be used to empirically investigate the extent of differences in early child investments and parenting practices between children/parents and how any differences relate to the later life outcomes of the children.

Impact of research: 
This project will identify the key parental investments in the very earliest years of life which lead to long-term economic success. The over-arching aim is to increase social mobility. To date, research in this domain has focused on experience from pre-school (age 3) onwards, neglecting the role of the very earliest years for human capital formation. We will add to the literature and policy understanding by more precisely quantifying how early-life investments and experiences help, or hinder, social mobility. We will quantify the relative size of the well-documented achievement gaps at school entry between advantaged and disadvantaged children, identifying when and, importantly, why they start to increase. The research will help to inform policy by uncovering which everyday parenting practices during infancy enhance outcomes later in life so we can make robust policy recommendations regarding the timing of targeted interventions in the earliest years of life, and even pre-birth. We will argue that early childhood should be an integral part of policy decisions; using this analysis to show that the role of the earliest phase of life for human capital formation is pivotal in understanding, and overcoming, the inequality and disadvantage that persist for many families. The force of this argument will be underpinned by data from four generations, uniquely available in the ALSPAC, which presents an exciting opportunity to expand our understanding of intergenerational mobility. Our findings will be of interest to policymakers in the Dept. for Education, the Dept. for Health and Social Care, and the Office of the Children’s Commissioner, as well as the Social Mobility Commission and we will actively engage with them. Understanding the role of the earliest interactions between parents and their children in the transmission of socio-economic status from one generation to the next will help in the design of policies aimed at increasing social mobility and widening opportunity, with the potential for significant long-term impact.
Date proposal received: 
Monday, 9 May, 2022
Date proposal approved: 
Monday, 16 May, 2022
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Intelligence - memory, Linkage, Parenting, Social science, Statistical methods

B4063 - Determinants of breastfeeding success and health inequalities - 10/05/2022

B number: 
B4063
Principal applicant name: 
Nancy McBride | MRC IEU (United Kingdom)
Co-applicants: 
Dr Luisa Zuccolo, Dr Carolina Borges, Emma Benham
Title of project: 
Determinants of breastfeeding success and health inequalities
Proposal summary: 

Breastfeeding is sustainable, the biological norm, and potentially life-saving, particularly for premature babies. Evidence-based strategies to support breastfeeding have been successful, but inequalities in breastfeeding rates are proving difficult to reduce, affecting the most vulnerable of mothers and babies. Successfully establishing and sustaining breastfeeding can be facilitated by both removing structural and cultural barriers, and overcoming individual challenges. Common factors such as obesity and depression/anxiety could play an important part in explaining some of the variability (and inequality) in breastfeeding duration. Conversely, maternal factors reflecting good mental and physical health could increase resilience to contexts with low systemic and cultural support for breastfeeding, such as the UK. However, the evidence on the individual determinants causally influencing successful and sustained breastfeeding is of poor quality. The identification of causal determinants of early cessation will improve breastfeeding support activities.

Impact of research: 
We hope to identify causal determinants of early cessation - this can then be used to improve breastfeeding support activities.
Date proposal received: 
Wednesday, 4 May, 2022
Date proposal approved: 
Tuesday, 10 May, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Birth outcomes

B4052 - Gaining Insights Into The Causal Effects Of Electronic Cigarette Use - 03/05/2022

B number: 
B4052
Principal applicant name: 
Jasmine Khouja | University of Bristol (United Kingdom)
Co-applicants: 
Dr Rebecca Richmond, Prof Marcus Munafo, Dr Elizabeth Prom-Wormley, Dr Megan Cooke, Dr Roseann Peterson, Dr Elizabeth Do, Prof Hermine Maes
Title of project: 
Gaining Insights Into The Causal Effects Of Electronic Cigarette Use
Proposal summary: 

E-cigarettes can help people stop smoking, but the long-term effects of e-cigarette / vaping initiation remain unknown. In this project, we will use our newly established Genetics, E-cigarette and Nicotine Consortium (GENiC) to identify genetic variants associated with vaping. This will provide information about the biological determinants of individual differences in vaping and support causal inference analyses into the downstream behavioural and health consequences of vaping.

At present, it is difficult to determine which genetic variants are specifically associated with vaping rather than smoking combustible cigarettes because most e-cigarette users have also smoked. However, data on non-smoking e-cigarette users are now emerging in large, genetically-informed cohort studies like ALSPAC, which enables – for the first time – the identification of genetic variants associated with vaping initiation (i.e., using e-cigarettes regularly or more than 100 times) in smoking-naïve young people.

We plan to use the available genetic data in ALSPAC and data relating to smoking and e-cigarette initiation to investigate whether a person’s genetic information can be used to predict e-cigarette initiation.

Impact of research: 
Identifying genetic variants associated with e-cigarette initiation will help us understand the genetic architecture of e-cigarette initiation and will provide opportunities for conducting causal analyses in a Mendelian randomisation (MR) framework. These causal analyses will help us to gain insight into the causal effects of e-cigarette use.
Date proposal received: 
Thursday, 21 April, 2022
Date proposal approved: 
Tuesday, 3 May, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., GWAS, Genome wide association study

B4061 - Prevention of high levels of depression across adolescence and young adulthood the role of active ingredients - 03/05/2022

B number: 
B4061
Principal applicant name: 
Isabel Morales-Muñoz | School of Psychology, University of Birmingham (United Kigndom)
Co-applicants: 
Prof Steven Marwaha, Dr Pavan Mallikarjun, Dr Alexander Zhigalov, Prof Christopher Yau, Dr David Wong
Title of project: 
Prevention of high levels of depression across adolescence and young adulthood: the role of active ingredients
Proposal summary: 

Depression is the leading cause of disability worldwide and is a major contributor to the overall global burden of disease, with more than 350 million people of all ages suffering from depression. Especially when recurrent and with moderate or severe intensity, depression may become a serious health condition. Further, we now know that many young people suffer from clinical depression. In fact, major depression is one of the most common mental health disorders in children and adolescents, with an estimated one year prevalence of 4-5% in mid-late adolescence and 5.6% in young people of 13-18 year old. Depression in young people is a precursor of adult depressive disorder which is strongly linked to poor physical health outcomes, lower income and increased unemployment, with half of those with lifelong recurrent depression starting to develop their symptoms before the age of 15 years. Thus, to recognize and treat depression in young ages is crucial. To sum up, depression is a substantial and largely unrecognized problem among young people that warrants an increased need and opportunity for identification and intervention. Understanding how specific factors might prevent and/od be effective in the treatment of depression in young people is crucial for the development of early intervention and treatment of depression among youths.
Depression results from a complex interaction of social, psychological, and biological factors. Recent attempts have been made by the Wellcome Trust to investigate the evidence for different active ingredients (i.e. those aspects of an intervention that drive clinical effect, are conceptually well defined, and link to specific hypothesised mechanisms of action) deemed to help prevent, treat, and manage depression in young people globally, including behaviours and activities, beliefs and knowledge, brain/body functions, cognitive and attentional skills, human connections, and socioeconomic factors. However, what is still unknown is which of these potential active ingredients and/or which combination of these active ingredients constitute a more accurate predictor for different groups of young people with depression, including those with high levels of depression.
A number of important issues need further investigation to aid early intervention in depression. First, most studies in young people with depression have focused on single time points, while very few studies have investigated the different trajectories of depression across adolescence and young adulthood, including young people with persistent high levels of depression. In addition, despite the recent attempt to identify specific active ingredients of effective interventions for depression, it is still unclear which of these active ingredients (and their combinations/interactions) are the most relevant to prevent depression across childhood and adolescence. For this reason, new statistical approaches, including predictive modelling are required and will help advance the field of early intervention in depression.
Therefore, the main purpose of this research proposal will be to characterize the most relevant active ingredients (and their combination) that prevent the development of persistent high levels of depression across adolescence and young adulthood. More specifically, we will aim to answer to the following main research questions: "What combination/s of active ingredients prevent the development of persistent high levels of depression across adolescence and young adulthood?"
To do this, we will use the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, which is a longitudinal birth cohort study, set in the UK, examining the determinants of development, health and disease during childhood and beyond.

Impact of research: 
The results that will come from this research will be of great relevance for young people with depression, for the following reasons: (i) the LCGA will allow detect a group of young people with persistent high levels of depression across adolescence and young adulthood; and by doing this, we will be able to detect the specific group of individuals who are at highest risk for depression; (ii) the regression analyses and the predictive modelling will be essential to characterize which are the most relevant active ingredients to be included in early intervention for depression; and (iii) finally, the digital triaging tool will have an impact in both the mental health researchers and young people, as this will allow better understand the specific characteristics and pathways that lead to specific interventions for different groups of young people with depression, including those at highest risk.
Date proposal received: 
Wednesday, 27 April, 2022
Date proposal approved: 
Tuesday, 3 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods

B4060 - UK LLC Association of COVID19 and Long COVID with disruption in employment and finances - 06/05/2022

B number: 
B4060
Principal applicant name: 
Richard Shaw | MRC/CSO Social and Public Health Sciences Unit, University of Glasgow
Co-applicants: 
Title of project: 
UK LLC: Association of COVID19 and Long COVID with disruption in employment and finances
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, 26 April, 2022
Date proposal approved: 
Wednesday, 27 April, 2022
Keywords: 
Social Science, Infection

B4055 - Physical Activity throughout Adolescence and Cardiac Structure and Function in Early Adulthood - 25/04/2022

B number: 
B4055
Principal applicant name: 
Linda O'Keeffe | University College Cork
Co-applicants: 
Dr Kate O'Neill, Shane McCarthy
Title of project: 
Physical Activity throughout Adolescence and Cardiac Structure and Function in Early Adulthood
Proposal summary: 

This project will examine whether adolescent physical activity is related to heart function in adulthood. This will be investigated by comparing physical activity levels and measurements of heart structure and function as collected in the Avon Longitudinal Cohort Study of Parents and Children.

Impact of research: 
Date proposal received: 
Tuesday, 19 April, 2022
Date proposal approved: 
Monday, 25 April, 2022
Keywords: 
Epidemiology

B4057 - Epigenetic signatures Association with hormone levels and age - 07/06/2022

B number: 
B4057
Principal applicant name: 
Reinhard Stoger | University of Nottingham (UK)
Co-applicants: 
Philippa Melamed, Maya Sudman, Gillian Bentley
Title of project: 
Epigenetic signatures: Association with hormone levels & and age
Proposal summary: 

Adrenarche is a developmental stage, occurring around ages 6-8 years, during which the adrenal glands produce increasing levels of the steroid hormone DHEAS. The function of this hormone, although extremely abundant in human circulation, is still unclear. Elevated levels of this hormone during this prepubertal stage are associated with earlier pubertal events and susceptibility to developing polycystic ovarian syndrome. Thus, we suspect this hormone has a substantial effect on various physiological systems, including the reproductive axis. Due to its chemical similarity to other steroid hormones, such as estradiol, we suspect it conveys its effect through the induction of epigenetic modifications, such as DNA methylation. Here, we would like to identify epigenetic modifications that are associated with DHEAS levels, using available data from girls at this developmental transition.

Impact of research: 
hypothesis testing: Is there a DNA methylation signature that reflects adrenarche? The human adrenarche signals the production and release into the general circulation of vastly elevated levels of DHEAS. Although occurring at a crucial stage in childhood development, the precise impact of this steroid on the reproductive axis and other physiological systems is very poorly understood. Identifying the changes in methylation that correlate with the levels of this hormone should indicate some of its targets and allow subsequent studies to establish the function and impact of adrenarche.
Date proposal received: 
Thursday, 21 April, 2022
Date proposal approved: 
Monday, 25 April, 2022
Keywords: 
Bioinformatics, Fertility/infertility

B4056 - How does university attendance impact on mental health trajectories of young people - 03/05/2022

B number: 
B4056
Principal applicant name: 
Peter Fonagy | UCL
Co-applicants: 
Mr Tom Osborn, Doctor Rob Saunders, Professor Will Mandy
Title of project: 
How does university attendance impact on mental health trajectories of young people
Proposal summary: 

The mental health of university students is a growing public health concern (1). Findings from population-based studies in the USA, UK and Norway point to a significant increase in mental distress among students over the last decade (2-5). Around 5% of young people in the UK have a diagnosis of either anxiety or depression, and the rate of people attending university has doubled in the past twenty years (6). For many the transition to university coincides with a developmentally high-risk period for the emergence of mental health concerns (7-9). This risk may be made worse by the need to adjust to a new social and academic environment whilst at the same time becoming financially independent (8, 10). This period could be particularly risky for students who have faced adversity, are socially disadvantaged (11), or for people who find it harder adjust to new social groups (8, 9). Few long-term studies have looked at these issues (12). While some evidence has shown how many students are likely to experience a mental disorder and use a mental health service at university (13); we do not currently know how much mental health need occurs prior to university attendance. By understanding this and any risk factors for the emergence and development of mental health need at this transition we could inform support-based prevention for students. This study aims to use data collected in ALSPAC to understand the risk university attendance poses on mental health and service use for a mental health reason among young people.

1. Barkham M, Broglia E, Dufour G, Fudge M, Knowles L, Percy A, et al. Towards an evidence-base for student wellbeing and mental health: Definitions, developmental transitions and data sets. Counselling and Psychotherapy Research. 2019;19(4):351-7.
2. Knapstad M, Sivertsen B, Knudsen AK, Smith ORF, Aarø LE, Lønning KJ, et al. Trends in self-reported psychological distress among college and university students from 2010 to 2018. Psychological Medicine. 2021;51(3):470-8.
3. Lipson SK, Lattie EG, Eisenberg D. Increased Rates of Mental Health Service Utilization by U.S. College Students: 10-Year Population-Level Trends (2007-2017). Psychiatric services (Washington, DC). 2019;70(1):60-3.
4. McManus S, Gunnell D. Trends in mental health, non‐suicidal self‐harm and suicide attempts in 16–24-year old students and non-students in England, 2000–2014. Social Psychiatry and Psychiatric Epidemiology. 2020;55(1):125-8.
5. Tabor E, Patalay P, Bann D. Mental health in higher education students and non-students: evidence from a nationally representative panel study. Social Psychiatry and Psychiatric Epidemiology. 2021;56(5):879-82.
6. Boero G, Nathwani, T., Naylor, R., Smith, J. Graduate Earnings Premia in the UK: Decline or Fall. Higher Education Statistics Agency (HESA): HESA; 2021.
7. Kessler RC, Amminger GP, Aguilar-Gaxiola S, Alonso J, Lee S, Ustün TB. Age of onset of mental disorders: a review of recent literature. Curr Opin Psychiatry. 2007;20(4):359-64.
8. Lei J, Brosnan M, Ashwin C, Russell A. Evaluating the Role of Autistic Traits, Social Anxiety, and Social Network Changes During Transition to First Year of University in Typically Developing Students and Students on the Autism Spectrum. Journal of Autism and Developmental Disorders. 2020;50(8):2832-51.
9. Adams KL, Saunders KE, Keown-Stoneman CDG, Duffy AC. Mental health trajectories in undergraduate students over the first year of university: a longitudinal cohort study. BMJ Open. 2021;11(12):e047393.
10. McCloud T, Bann D. Financial stress and mental health among higher education students in the UK up to 2018: rapid review of evidence. Journal of Epidemiology and Community Health. 2019;73(10):977-84.
11. Cullinan J, Walsh S, Flannery D. Socioeconomic Disparities in Unmet Need for Student Mental Health Services in Higher Education. Applied Health Economics and Health Policy. 2020;18(2):223-35.
12. Lewis GM, T. Callender, C. Higher Education and Mental Health: Analyses of the LSYPE cohorts: research reports. In: Education. Do, editor. 2021.
13. Eisenberg D, Hunt J, Speer N. Help seeking for mental health on college campuses: review of evidence and next steps for research and practice. Harvard review of psychiatry. 2012;20(4):222-32.

Impact of research: 
The findings from research aim to be published in a peer reviewed open access journal where the implications and recommendations for health service practice and policy can be disseminated. Findings will be shared at relevant academic and health service conferences. The authors are part of current policy initiatives at UCL Partners, the National Institute of Health Research Applied Research Collaboration, and PsychUP for Wellbeing at UCL in London and the UK to strengthen and implement policy initiatives aiming to improve student mental health. The results will directly inform the implementation of these initiatives.
Date proposal received: 
Wednesday, 20 April, 2022
Date proposal approved: 
Monday, 25 April, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity

B4058 - The associations between dietary pattern and immune response the mediating roles of metabolic syndrome - 03/05/2022

B number: 
B4058
Principal applicant name: 
Ruifang LI | Leiden University Medical Center (Netherlands)
Co-applicants: 
Dr. Ruifang Li, Dr. Dennis Mook-Kanamori
Title of project: 
The associations between dietary pattern and immune response: the mediating roles of metabolic syndrome
Proposal summary: 

A healthy, balanced diet is important for keeping metabolic health and supporting immune system. Obesity is associated with a wide range of metabolic syndromes, including dyslipidemia, hyperglycemia and fatty liver. Hyperglycemia and lipid accumulation may provoke lipid oxidation and further lead to an overproduction of cytokines, hyperactivation of complement system and activation of coagulation system, which all serve as immunological triggers to severe infection of COVID-19 as well as other infectious diseases. In the current proposed project, we will explore all the potential associations between dietary patterns and immune response, as well as potential metabolic-related mediators to explain the observed associations between diet and immune response through mediation analysis in several population-based cohort studies.

Impact of research: 
This research activity will be the most extensive research to triangulate evidence from four independent cohort studies with diverse ethnicity backgrounds, dietary patterns and socioeconomic status, to disentangle casual pathways, which will provide insights into further dietary intervention studies to boost immune function and alleviate disease risks.
Date proposal received: 
Monday, 25 April, 2022
Date proposal approved: 
Monday, 25 April, 2022
Keywords: 
Epidemiology, Diabetes, Hypertension, Infection, Obesity, Metabolomics, NMR, Proteomics, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Immunity, Liver function, Metabolic - metabolism, Nutrition - breast feeding, diet

B4038 - Psychosocial and Biological influences on sexual orientation disparities in mental health outcomes - 10/05/2022

B number: 
B4038
Principal applicant name: 
Yin Xu | Sichuan University (China)
Co-applicants: 
Dr. Qazi Rahman, Dr. Yidan Ma
Title of project: 
Psychosocial and Biological influences on sexual orientation disparities in mental health outcomes
Proposal summary: 

Non-heterosexual (bisexual, lesbian, gay, and asexual) adolescents are at greater risk of common mental health disorders compared to heterosexual adolescents. The dominant theoretical framework used to explain the elevated rates of mental disorders among non-heterosexuals is minority stress theory. However, this model cannot fully explain sexual orientation disparities in mental health outcomes. Thus, other mechanisms or explanations, may help explain the sexual orientation disparities in mental health outcomes should be further explored. In addition, many adult mental health problems begin in childhood or adolescence. Non-heterosexual adolescents may be at greater risk of poorer mental health even in early childhood compared with heterosexual adolescents, which cannot be explained by the minority stress theory since when sexual identity development is nascent. However, the underlying mechanisms remained under-explored. Thus, this project aims to further test the psychosocial and biological influences on the sexual orientation disparities in mental health outcomes, especially in childhood, early adolescence, and the developmental trajectories from childhood to adolescence.

Impact of research: 
Date proposal received: 
Monday, 11 April, 2022
Date proposal approved: 
Friday, 22 April, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity

B4034 - Using genetics to understand causal mechanisms underlying pregnancy outcomes for mothers and babies - 21/04/2022

B number: 
B4034
Principal applicant name: 
Rachel Freathy | University of Exeter (UK)
Co-applicants: 
Miss. Annika Jaitner, Prof. Jack Bowden, Prof. Krasimira Tsaneva-Atanasova
Title of project: 
Using genetics to understand causal mechanisms underlying pregnancy outcomes for mothers and babies
Proposal summary: 

**Please note that this project is linked to our existing B3392 project and will mostly require variables that we already have in Exeter in the B3392 dataset.**
References to previously published work in the summary below are given as PubMed IDs.

Maternal smoking during pregnancy is associated with various adverse pregnancy outcomes. Despite a strong public health message, many pregnant women continue to smoke. Studies and data analysis indicate that maternal smoking is associated with a reduction in offspring birth weight (PMID: 33173933 and PMID: 22956269), which is likely to be due to an adverse effect of smoking on placental function. Placental weight is often used as a convenient indicator of placental function (PMID: 32421535). However, information on the effect of smoking during pregnancy on placental weight is limited. The literature reports both lower and higher placental weights for women who smoked during pregnancy, relative to those who did not smoke (PMID: 32421535 and PMID: 29947760). We aim to gain a better understanding of the risk of smoking during pregnancy by using genetics to test whether smoking is causally related to placental weight, and to better understand the underlying mechanisms connecting smoking, placental weight and birth weight. So far, the team in Exeter have used ALSPAC and other studies to identify genetic variations in both mothers and babies that are associated with birth weight (PMID: 31043758), to show that genetic variation influences how likely women are to quit smoking in pregnancy (PMID: 19429911), and to show that this same genetic variation influences birth weight via its effect on smoking (PMID: 22956269). The current project will build on those findings and relate smoking, birth weight and placental weight.

Impact of research: 
High impact publications improving understanding of mechanisms of how smoking relates to fetoplacental growth in human pregnancy. New tools and methods for causal mediation and MR analysis of family data, that can be applied more widely by researchers in the field.
Date proposal received: 
Tuesday, 29 March, 2022
Date proposal approved: 
Thursday, 21 April, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, GWAS, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods, Epigenetics, Fathers, Genetic epidemiology, Genetics, Genome wide association study, Growth, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics

B4049 - Cardiovascular risk factor trajectories and subclinical phenotypes in young people with and without type 1 diabetes - 21/04/2022

B number: 
B4049
Principal applicant name: 
Scott Chiesa | UCL (UK)
Co-applicants: 
Dr Loredana Marcovecchio
Title of project: 
Cardiovascular risk factor trajectories and subclinical phenotypes in young people with and without type 1 diabetes
Proposal summary: 

Cardiovascular disease (CVD) is the primary cause of premature morbidity and mortality in type 1 diabetes, with this effect particularly pronounced in those diagnosed at a younger age. The magnitude of this problem has recently been starkly highlighted by findings from the Swedish National Diabetes Register, where patients diagnosed with diabetes between 1 and 10 years of age were found to have a 10× higher risk of future acute myocardial infarction compared to those diagnosed between the ages of 26 and 30 years, and over a 30× higher risk than the general population. These and other data suggest that adolescence may be a particularly crucial time in the development of future CVD complications in type 1 diabetes, and that effective intervention at this age may offer long-lasting benefits for cardiovascular health.

While compromised glycaemic control represents the major risk factor for CVD complications in type 1 diabetes, individuals living with the disease are also exposed to many other well-established and potentially modifiable risk factors faced by the population at-large. Obesity is a well-established causal driver of subclinical disease in the young, is known to track into adulthood, and therefore represents one of the major risk factors in early-life for future risk of CVD. Although individuals with type 1 diabetes have traditionally been considered to be a relatively lean population, recent evidence has shown that obesity rates in this group are now similar or possibly even higher than in the general population, with an alarmingly high prevalence in children and adolescents.

For the last 14 years, our group have tracked, genotyped, and extensively phenotyped a cohort of adolescents with type 1 diabetes; first as part of a randomised clinical trial (The Adolescent type 1 Diabetes cardio-renal Intervention Trial - AdDIT), and then as part of a long-term epidemiological study (AdDIT Follow-Up). We now wish to use this data alongside that collected over the same timespan in ALSPAC to address the following aims and objectives:

Impact of research: 
High impact journal publications and conference proceedings. Future major funding applications investigating impact of modifiable risk factors in T1D.
Date proposal received: 
Tuesday, 12 April, 2022
Date proposal approved: 
Thursday, 21 April, 2022
Keywords: 
Epidemiology, Diabetes, Obesity, Blood pressure, BMI, Cardiovascular, Puberty

B4046 - Investigating the association between birthweight and intellectual disability - 22/04/2022

B number: 
B4046
Principal applicant name: 
Paul Madley-Dowd | University of Bristol (United Kingdom)
Co-applicants: 
Dr Dheeraj Rai, Rhys Higginson
Title of project: 
Investigating the association between birthweight and intellectual disability
Proposal summary: 

Cognitive delay has previously been found to be associated with low birthweight. Little research has been conducted to explore the specific association between low birthweight and intellectual disability (defined as having an arrested or incomplete development of the mind alongside functional impairment in facets that contribute to overall intelligence such as cognition, language and social ability), particularly among populations that were born at an appropriate gestational age. The current project will explore the observational association in ALSPAC before going on to investigate potential moderating factors (factors that influence the strength of the effect). We will then investigate whether the association is likely to reflect a causal effect by using techniques such as Mendelian Randomization.

Impact of research: 
The research will be used as part of a Master's dissertation for the MSc in Epidemiology. Any associations identified will contribute towards the literature on the etiology of intellectual disability which, so far, has been under researched.
Date proposal received: 
Tuesday, 19 April, 2022
Date proposal approved: 
Thursday, 21 April, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Learning difficulty, Statistical methods, Development

B4041 - What is the association between child intellectual disability and later parental mental health - 22/04/2022

B number: 
B4041
Principal applicant name: 
Paul Madley-Dowd | University of Bristol (United Kingdom)
Co-applicants: 
Dr Dheeraj Rai, Lamya Alhomaydan
Title of project: 
What is the association between child intellectual disability and later parental mental health?
Proposal summary: 

Evidence has accumulated that the parents of children with intellectual disabilities are at increased risk of adverse mental health outcomes including depression and anxiety. Research in the field is currently attempting to explore the nature of this association, trying to identify which parents are most at risk and to what extent is the association confounded by the family environment, genetics and prior episodes of adverse mental health. The ALSPAC cohort has not been used to explore this research question so far and has substantial information on the family environment, parental mental health before and after the development of an intellectual disability in the child, maternal genetics and child behaviours. Such information may be useful for identifying modifiable targets for intervention or exploring which parents are most at risk.

Impact of research: 
Our work will be of relevance to commissioners of health and social care. The results will help in understanding of the mental health care needs of individuals who care for children with ID and identification of modifiable targets for intervention will be important for preventing mental health problems in the community of carers for children with ID.
Date proposal received: 
Tuesday, 19 April, 2022
Date proposal approved: 
Thursday, 21 April, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Cognitive impairment, Statistical methods

B4044 - Maternal employment and childcare associated with socio-emotional health in children - 20/04/2022

B number: 
B4044
Principal applicant name: 
Yassaman Vafai | BIHR (United Kingdom)
Co-applicants: 
Prof Jordi Julvez, Prof Deborah Lawlor, Ahmed Elhakeem
Title of project: 
Maternal employment and childcare associated with socio-emotional health in children
Proposal summary: 

Socio-emotional outcomes such as internalizing and externalizing behaviours, and ADHD in young children are associated with subsequent adverse outcomes in adolescence and adulthood such as poor school performance, depression, and antisocial behaviours. Growing empirical evidence suggests that many factors within the home environment are associated with the onset of these outcomes in children. One of these factors is maternal employment status, which for many families serves a critical purpose through increasing financial resources of the family, enhancing women’s careers and independence, and encouraging a more-equal gender role within the family. Nevertheless, some literature has raised concerns regarding the effect of maternal employment on children’s socio-emotional health, although the findings are inconsistent. For instance, some studies found that maternal employment within the first year of childbirth is associated with development of externalizing and internalizing behaviours in children. A few studies found no association, while in some others maternal employment led to improved socio-emotional health especially among minority and low-income populations.The discrepancies in findings can be due to differences in study design, exposure and outcome measurements, and the contextual characteristics of settings. In particular, maternity leave and childcare policies likely play crucial moderating roles in the association between maternal employment and child outcomes.There is evidence that the type, initiation (with earlier initiation due to shorter maternity leave) and quality of childcare impact child development. However, data on the potential additive effect of maternal employment and childcare on children’s socio-emotional health outcomes are scarce. Therefore, to better understand the role of maternal employment and childcare on children’s socio-emotional health and to inform public health policies and interventions related to maternity leave and childcare, new research examining the effect of these factors on children’s socio-emotional health is warranted.

Impact of research: 
To inform public health policies in regards to maternity leave and childcare as well as women's rights
Date proposal received: 
Monday, 11 April, 2022
Date proposal approved: 
Wednesday, 20 April, 2022
Keywords: 
Epidemiology, Mental health, Statistical methods, Social science

B4045 - Association between adiposity and diabetes with inflammation - 20/04/2022

B number: 
B4045
Principal applicant name: 
Vanessa Tan | Integrative Epidemiology Unit, University of Bristol
Co-applicants: 
Lucy Goudswaard, Professor Nicholas Timpson
Title of project: 
Association between adiposity and diabetes with inflammation
Proposal summary: 

Increased adiposity and Type 2 diabetes (T2D) have both been associated with increased risk of developing certain cancers and are both becoming increasingly prevalent globally. Although adiposity, T2D and cancer share many risk factors, the biological pathways linking adiposity and T2D to cancer remain poorly understood.

Chronic low-grade inflammation, characterised by abnormal cytokine production, is associated with both adiposity and T2D. Observational studies have suggested that increased adiposity and hyperglycaemia associated with diabetes induce the production of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-6 which have key roles in cancer. This observation has led to the hypothesis that chronic inflammation might be a potential mechanism linking adiposity and T2D to cancer. However, due to the inherent limitations of observational research such as reverse causation and confounding, findings from observational studies need to be interpreted with caution. Furthermore, previous studies have used a single ‘baseline’ measurement of adiposity, T2D and inflammation and cannot fully account for the time-dependent variability in these measurements which may lead to a biased estimation.

Mendelian randomization is an analytical approach where genetic variants reliably associated with risk factors of interest are used as proxy measures to re-estimate the associations between an exposure and an outcome where some of the limitations of observational epidemiology are reduced. In this investigation, we would like to use genetic variants associated with adiposity, T2D and related glycaemic traits to investigate the estimated causal association between adiposity and T2D with inflammatory proteins (measured using the Olink inflammatory panel). We will also use longitudinal measures of inflammatory proteins to investigate whether the relationship between BMI/T2D with inflammation changes over time (across childhood and young adulthood) and potentially identify patterns in the relationship between BMI/T2D and inflammation which may be relevant to cancer development.

Impact of research: 
This project will contribute to the identification of inflammatory proteins associated with adiposity and T2D, and therefore, to our understanding of mechanisms underlying the observed associations between adiposity and T2D with health outcomes such as cancer.
Date proposal received: 
Tuesday, 5 April, 2022
Date proposal approved: 
Wednesday, 20 April, 2022
Keywords: 
Epidemiology, Cancer, Proteomics, BMI, Genetic epidemiology, Mendelian randomisation

B4048 - Prospective relationships between incontinence and common mental health problems in adolescents from a UK cohort - 20/04/2022

B number: 
B4048
Principal applicant name: 
Carol Joinson | PHS (UK)
Co-applicants: 
Dr Naomi Warne, Katie Gordon
Title of project: 
Prospective relationships between incontinence and common mental health problems in adolescents from a UK cohort
Proposal summary: 

Incontinence – both urinary and faecal – is a common childhood occurrence. Whilst most children obtain daytime bladder control by 3-years, and night-time bladder control at 4-6-years, it is not uncommon for school-age children to experience some form of incontinence (1). Indeed, parents of 7 ½ year-olds in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort reported 15.5% experienced bedwetting, and 7.6% experienced daytime wetting. Incontinence can seriously undermine quality of life, and psychological distress may occur if children become aware that incontinence is unusual for children of their age and/or following negative reactions from family or peers (1). Further, 20-40% of children in attendance of continence clinics meet diagnostic criteria of at least one psychiatric condition (2).

It is commonly believed that issues with continence during childhood will resolve with age (3). However, epidemiological studies report 2-3% of adolescents experience urinary incontinence, and 1-1.5% experience faecal incontinence (3). There is also evidence that adolescents experience more severe forms of incontinence compared to younger children. Indeed, a cross-sectional study of 16,512 children in Hong Kong found a greater proportion of frequent bedwetting (≥3 wet nights/week) accompanied with daytime wetting and other lower urinary tract symptoms in 11-19-year olds compared to 5-10-year olds (4).

Incontinence in adolescence is particularly problematic because this is a sensitive time period in which identity and body image are formed, and peer acceptance is highly valued (1). The shame and stigma associated with incontinence may affect friendships and participation in social activities, which may in turn increase risk of developing psychosocial problems. Psychosocial problems during adolescence have been linked to future adverse mental health and social outcomes, including poor academic attainment, low self-esteem, depression, and suicidal behaviours (1,3).

Whilst some studies have investigated whether childhood incontinence is a risk factor for poor psychosocial outcomes in adolescence, few consider the impact of incontinence issues that persist beyond childhood. Further research is therefore required to investigate the relationship between continence issues in adolescence and adverse mental health outcomes.

1. Grzeda MT, Heron J, von Gontard A, Joinson C. Effects of urinary incontinence on psychosocial outcomes in adolescence. European Child and Adolescent Psychiatry. 2017 Jun;26(6):649–58.
2. Heron J, Grzeda MT, von Gontard A, Wright A, Joinson C. Trajectories of urinary incontinence in childhood and bladder and bowel symptoms in adolescence: prospective cohort study. BMJ Open. 2017;7(3):e014238.
3. Whale K, Cramer H, Joinson C. Left behind and left out: The impact of the school environment on young people with continence problems. British Journal of Health Psychology. 2018;23(2):253–77.
4. Yeung CK, Sreedhar B, Sihoe JDY, Sit FKY, Lau J. Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study. BJU International. 2006;97(5):1069–73.

Impact of research: 
This masters project is part of a wider MRC project examining bidirectional relationships between incontinence and mental health. The findings will help to raise awareness of the need for psychological support for young people with continence issues.
Date proposal received: 
Monday, 11 April, 2022
Date proposal approved: 
Wednesday, 20 April, 2022
Keywords: 
Epidemiology, Incontinence, Statistical methods, Development

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