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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B3672 - Urban exposome during pregnancy and early childhood and child emotional and behavioural problems - 15/12/2020

B number: 
B3672
Principal applicant name: 
Monica Guxens | ISGlobal
Co-applicants: 
Anne-Claire Binter, Dr
Title of project: 
Urban exposome during pregnancy and early childhood and child emotional and behavioural problems
Proposal summary: 
Impact of research: 
Date proposal received: 
Tuesday, 15 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Epidemiology

B3678 - Consortium Against Pain InEquality CAPE - The impact of adverse childhood experiences on chronic pain responses to treatment - 17/12/2020

B number: 
B3678
Principal applicant name: 
Gary Macfarlane | University of Aberdeen (United Kingdom)
Co-applicants: 
Professor Tim Hales, Dr Line Caes
Title of project: 
Consortium Against Pain InEquality (CAPE) - The impact of adverse childhood experiences on chronic pain & responses to treatment
Proposal summary: 

The World Health Organisation describes adverse childhood experiences (ACEs) including abuse, neglect, violence and other household dysfunction, as the commonest and most intense childhood stressors. About half of us experience at least one and those exposed to several are likely to experience more health problems later in life, including chronic pain. There is a strong relationship between exposure to multiple ACEs and social deprivation, and additional associations with having a young mother or being male. Although there is increasing evidence that ACEs contribute to health inequalities, there is no widespread screening to identify interventions. Reasons for this include the limited range of ACEs in existing methods of assessment and little consideration of other factors that may contribute to vulnerability.

CAPE will develop a thorough questionnaire for assessing ACEs to enrich large population cohort data. This information will be linked to prescribing, social care records, neuroimaging, genetics and tissue samples, enabling identification of biopsychosocial factors that create vulnerability to chronic pain and adverse responses to treatment.

Impact of research: 
We will create a richly phenotyped datasets linking ACE exposure to pain, prescribing and adverse outcomes. Within CAPE, we will examine whether the increased burden of chronic pain, which disproportionately affects those exposed to multiple ACEs, leads to higher levels of opioid prescribing and associated adverse events. We anticipate that this will enable development of personalised pain management approaches and inform prescribing guidelines. We will engage with the Drug Deaths Task Force (https://www.gov.scot/groups/drug-deaths-task-force/) to develop evidence-based public health policy.
Date proposal received: 
Monday, 14 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Keywords: 
Epidemiology, Pain, Childhood - childcare, childhood adversity

B3673 - Maternal exposure to urban environmental stressors and depression in the postnatal period - 09/12/2020

B number: 
B3673
Principal applicant name: 
Tim Cadman | Integrate Epidemiology Unit (UK)
Co-applicants: 
Dr Marie Pedersen, Katrine Strandberg-Larsen, Deborah Lawlor
Title of project: 
Maternal exposure to urban environmental stressors and depression in the postnatal period
Proposal summary: 

Maternal postnatal depression is estimated to affect 6 – 38% of women in high income countries. Not only is it by nature distressing, it is also associated with health risks to the child. We need to know more about what causes postnatal depression in order to inform policy to prevent it.

One set of factors which could be important are aspects of the city environment such as noise, air polution and access to natural spaces. The period following birth is a particular vulnerable time and these factors could have a negative impact on maternal mental health. For example, air polution could affect the brain which could lead to an increased risk of depression. Road traffic noise could disrupt sleep leading to increased stress, and a lack of access to natural spaces could reduce opportunities to socialise and relax.

Whilst there is some evidence that these aspects of the city environment are related to depression in adults, very few studies have explored their relevance for postnatal depression. In this study we aim to use a large data resource including many European cities to investigate whether exposure to these different aspects of the city environment increases the risk of postnatal depression.

Impact of research: 
It will increase understanding on the extent to which the urban environment affects postnatal depression, which could inform preventative policies.
Date proposal received: 
Friday, 4 December, 2020
Date proposal approved: 
Tuesday, 8 December, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B3665 - Early life exposure to cardiovascular risk factors and cerebral structure and function in young adults - 02/12/2020

B number: 
B3665
Principal applicant name: 
Scott Chiesa | UCL (UK)
Co-applicants: 
Dr Sana Suri, Professor Klaus Ebmeier, Professor John Deanfield, Georgios Georgiopoulos
Title of project: 
Early life exposure to cardiovascular risk factors and cerebral structure and function in young adults
Proposal summary: 

Certain behavioural (e.g. diet, smoking, physical activity) and physiological (e.g. obesity, cholesterol, glycaemic control, blood pressure) risk factors have long been known to increase risk of atherosclerotic CVD in later life. Although clinical events rarely occur prior to middle-age, our group have previously shown that early signs of damage to the vasculature can be detectable from as early as childhood (Charakida et al 2012 JACC; Dangardt et al 2019 Lancet Child and Adolescent Health; Chiesa et al JACC Imaging 2019), and that cumulative exposure to this damage across the lifespan likely represents one of the biggest causes of later-life events.

Intriguingly, recent research strongly suggests that these modifiable health behaviours and risk factors may also contribute to another of the world's most pressing global health crises – dementia. A wealth of recent research supports the concept that the development and progression of cognitive decline and eventual dementia can be slowed or perhaps even prevented by addressing various risk factors more commonly linked to CVD (Livingstone et al 2020 Lancet). The implementation of early-life prevention strategies to improve heart health may therefore also provide dual benefits for long-term brain health.

Our group and others have recently contributed to accumulating evidence suggesting that it is exposure to these CV risk factors earlier in the lifespan which appear to relate most strongly to risk of cerebral (i.e. brain) disease risk in later life. These findings suggest that although dementia diagnoses are almost exclusively made in older age, they may in fact represent the end result of cumulative damage to brain tissues which have been sustained over decades previously. However, how early this damage starts and what factors are responsible for its appearance is currently unknown, as very few populations are available in which detailed brain scans have been carried out on a young population with wide-ranging CVD risk factors.

Impact of research: 
It is currently not known how early in life adverse changes within the cerebral tissues and circulation begin to appear, and whether the brain may be negatively impacted by childhood and adolescent exposure to risk factors in the same way as we have previously shown in the arteries. This study will provide a unique opportunity to investigate the effect that cumulative exposure to these risk factors has on markers of cerebral damage which are known to link to cognitive decline in older populations, and may therefore provide the first evidence of an adverse impact on the brain from poor health behaviours in the earliest stages of life. These findings are likely to be of wide interest to the scientific community and may inform prevention strategies for cerebral health by identifying a previously unappreciated but crucial window for targeting poor health behaviours.
Date proposal received: 
Tuesday, 24 November, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Epidemiology, Cognitive impairment, Hypertension, Obesity, CVD, Medical imaging, epidemiology, Ageing, Blood pressure, BMI, Cardiovascular, Cognition - cognitive function, Equipment - MRI, Neurology

B3670 - National Core Studies ARQ7 Investigating the socio-economic impact of COVID-19 - 02/12/2020

B number: 
B3670
Principal applicant name: 
Laura Howe | University of Bristol (United Kingdom)
Co-applicants: 
Dr. Kate Northstone , Professor Nicholas Timpson, Dr. Jazz Croft, Gareth Griffith, Dr. Alex Kwong
Title of project: 
National Core Studies ARQ7: Investigating the socio-economic impact of COVID-19
Proposal summary: 

The COVID-19 pandemic has affected daily life since the start of the pandemic in March 2020. The adoption of viral suppression measures, including social distancing and both localised and national lockdowns, has led to an increase in economic inactivity and changes to the labour market. According to Office of National Statistics estimates (ONS October 2020), since March 2020 the rate of economic growth in the United Kingdom has been slowing and unemployment has risen sharply with the most dramatic decline being during the early stages of the pandemic. The effect of these changes to employment status (increased/decreased hours, periods of furloughed employment, redundancy, change in employment) on physical and mental health and health behaviours (alcohol consumption, exercise, diet) during the pandemic is currently unclear. An important consideration is whether different social factors (e.g. gender, ethnicity, economic situation, clinical vulnerability to COVID-19) contribute to poorer health and wellbeing during the pandemic because of changes in employment status. Understanding how social inequalities may contribute to changes in employment and health outcomes can help to identify vulnerable groups for additional support to reduce health difficulties and promote wellbeing.

Using data from Children of the 90s, we can examine participants’ employment status, wellbeing, and health behaviours before and during the pandemic to help us answer these questions and inform social and economic policy.

Impact of research: 
Findings will contribute to the currently limited evidence base in this area. We will be able to identify groups that have particularly been affected by the pandemic and inform the need for responsive behavioural change interventions to alleviate adverse impacts.
Date proposal received: 
Tuesday, 1 December, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Mental health, Obesity, Statistical methods, BMI, Physical - activity, fitness, function, Employment, COVID-19

B3669 - Exploring epigenetic and phenotypic associations with genetic liability to juvenile idiopathic arthritis - 02/12/2020

B number: 
B3669
Principal applicant name: 
Gemma Sharp | MRC IEU, UoB
Co-applicants: 
Dr Sarah Clarke
Title of project: 
Exploring epigenetic and phenotypic associations with genetic liability to juvenile idiopathic arthritis
Proposal summary: 

Juvenile idiopathic arthritis (JIA) is the most common rheumatic condition of childhood, but remains a relatively rare condition. Whilst there is growing knowledge about JIA disease management, we have very limited knowledge about the wider impacts of the condition, particularly in adolescence and adult life. For example observational data suggests that JIA patients have adverse educational attainment levels and employment outcomes. There is also growing concern about wider health implications of JIA such as cardiovascular disease risk, similar to that seen for adult rheumatoid arthritis patients, although long term follow-up data of JIA patients into adulthood is very limited. Within this PhD a range of different techniques are being used to explore causes and effects of JIA across the life course using observational and ‘omic data. Our earlier work has shown associations between JIA and a number of other health outcomes, however outcome datasets have all derived from older adult populations. Building on earlier work, this project aims to examine the association between the level of the genetic risk of JIA (using polygenic risk scoring) and a range of clinical (e.g. cardiovascular risk factors), biological (e.g. circulating CRP levels), metabolic (eg circulating lipids) and molecular (e.g. changes to DNA methylation) outcomes during childhood and early adulthood. This will allow us to identify potential JIA associated comorbidity earlier in disease to a) allow earlier risk stratification of patients and b) allow underlying mechanisms of comorbidity to be explored.

Impact of research: 
Understanding the wide health impact of JIA on patients with the condition will enable a more targeted and holistic approach to their care with regards to risk stratification and modification. This will be particularly important as JIA patient transition from paediatric to adult health services.
Date proposal received: 
Monday, 30 November, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Epidemiology, Juvenile Idiopathic Arthritis, EWAS, pheWAS, Childhood - childcare, childhood adversity, Epigenetics, Genetic epidemiology, Mendelian randomisation

B3666 - Characterisation determinants mechanisms and consequences of long COVID providing the evidence base for health care services - 14/04/2021

B number: 
B3666
Principal applicant name: 
Nishi Chaturvedi | University College London (UK)
Co-applicants: 
Prof Nicholas Timpson, Prof jonathan Sterne, Prof John Macleod, Andy Boyd
Title of project: 
Characterisation, determinants, mechanisms and consequences of long COVID – providing the evidence base for health care services
Proposal summary: 

Over 95% of COVID-19 (C-19) infections are not admitted to hospital. Yet debilitating physical and mental health symptoms of long COVID are reported frequently, their degree not wholly related to symptom severity. The diagnosis of long COVID itself, the categorisation into distinct syndromes with implications for identification of high risk groups, tailoring of interventions, and likelihood of recovery or adverse outcomes are poorly described. Our proposal will address these gaps, and help inform guidelines.

Impact of research: 
The characterisation and recording of long COVID
Date proposal received: 
Thursday, 26 November, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Epidemiology, Infection, Epidemiological definition and dissection of longCOVID, COVID epidemiology

B3667 - Predicting pubertal timing in boys and girls using clinical data and polygenic risk scores - 02/12/2020

B number: 
B3667
Principal applicant name: 
Despoina Manousaki | Research Center of the CHU Sainte Justine, University of Montreal (Canada)
Co-applicants: 
Nahid Yazdan Panah, Mojgan Yazdan Panah, Nicholas Timpson, Ken Ong, John Perry, Brent Richards
Title of project: 
Predicting pubertal timing in boys and girls using clinical data and polygenic risk scores
Proposal summary: 

Children with precocious puberty are defined as girls with breast development before age 8 years and boys with testicular enlargement before age 9 years (which corresponds to minus 2 standard deviations (SD) compared to the average age of these changes in both sexes). Earlier age at pubertal start has been associated with earlier age at first vaginal bleeding (menarche) in girls and earlier age at voice change in boys, and with long-term consequences, including shorter adult height and psychosocial adverse effects. Although more frequent in certain ethnicities, the prevalence of precocious puberty in girls is constantly increasing worldwide, following the increase in cases of pediatric obesity. Most children with precocious puberty do not present any endocrine, metabolic, neurologic or neurosurgical condition explaining their earlier pubertal start (these cases are defined as “idiopathic” precocious puberty), but extensive work up (including specific hormone measurements and radiological exams) is routinely performed to eliminate such conditions. An important portion of children with precocious puberty will be considered for treatment with puberty-blocking pharmacological agents, without clear evidence that these treatments will increase their adult height.
Late puberty is defined as an absence of breast development by age 13 in girls (or absence of menarche by age 15), and an absence of testicular enlargement before age 14 in boys. This phenomenon is more frequent in boys, in most of which no pathological cause is detected, and these children will end up developing a spontaneous puberty and achieve a normal adult height. Nonetheless, these children are often referred for endocrine evaluation and investigated to eliminate an underlying medical condition.
Given that age at pubertal start in the population follows a Gaussian distribution, 2.3% of normal healthy children will start their puberty at and age below 2 SD below the mean for each sex, and another 2.3% will start their puberty above 2SD above this mean. Defining which children with precocious or late puberty correspond to these 2.3% of the general population is important, since this would avoid unnecessary investigations and treatment in these patients.
Pubertal traits (age at breast development and menarche in girls, testicular enlargement and voice change in boys, age at pubertal growth spurt in both sexes), have a polygenic nature, and an overlapping genetic architecture in boys and girls. It has been estimated that about 50% of variation in age at menarche can be attributed to genetics. Polygenic risk scores (PRS) have been demonstrated to have an improving ability to identify individuals at significantly high/low predisposition towards complex diseases. Therefore, it has become possible to identify individuals who will lie at the extreme distribution of a trait, such as age at menarche in girls or age at voice change in boys.
Therefore, we posit that PRS for age at menarche in girls or age at voice change in boys, in combination with clinical risk factors (such as increased body mass index) may be able to effectively predict children diagnosed as having idiopathic precocious puberty and in which no further investigation or treatment would be required to achieve a normal adult height (within their parental target height). Also, the same scores could identify children in the opposite extreme of the normal distribution, ie children with late puberty.

Impact of research: 
Our study can potentially stratify for risk of IPP or late puberty among children, based on a score derivable at no risk and low cost. Such a stratification is likely to substantially reduce the socioeconomic burden on many families whose children have IPP or late puberty while optimizing allocation of medical resources. Our study may also illustrate whether the genetic factors captured by the PRS are constantly associated with pubertal development stages since early childhood, or when they start to become associated. Finally, by objectifying the portion of the variance in pubertal traits explained by genetic factors, we will draw interesting conclusions on the “nature vs nurture” of precocious puberty- since it is has been shown that lower socio-economic status and exposure to environmental chemicals predispose to earlier pubertal start. This is likely to shed new light upon investigations on puberty, growth and development.
Date proposal received: 
Friday, 27 November, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B3668 - The relationship between parenting and mental health the role of genetic nurture and child evocative effects across contexts - 02/12/2020

B number: 
B3668
Principal applicant name: 
Marcus Munafò | University of Bristol
Co-applicants: 
Miss Amy Campbell, Dr Hannah Sallis, Dr Rebecca Pearson
Title of project: 
The relationship between parenting and mental health: the role of genetic nurture and child evocative effects across contexts
Proposal summary: 

There are known links between parenting behaviour and mental health outcomes in children. However, it is not known the extent to which the genetics of the mother and the child independently interact to influence children’s future mental health. Genetics can influence child outcomes in multiple different ways:
1. Genetic variants which increase the risk of developing a mental health disorder can be passed directly from mother to child
2. A mother’s genetics can affect the way that she parents her child
3. A child’s genetics can cause them to behave in certain ways which evoke certain responses from their mother
Across four studies, I will investigate the role of genetics in the relationship between parenting and mental health outcomes.

Impact of research: 
This PhD will contribute to the overall understanding of the intergenerational transmission of mental health, through parenting and genetic factors. This improved aetiological understanding can then facilitate identification of intervention targets and intervention design.
Date proposal received: 
Monday, 30 November, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Computer simulations/modelling/algorithms, Psychology - personality

B3658 - Evaluating longitudinal invariance in measures of child and adolescent mental health and wellbeing across development - 01/12/2020

B number: 
B3658
Principal applicant name: 
Aja Murray | University of Edinburgh (UK)
Co-applicants: 
Dr Tom Booth, Dr Graciela Muniz-Terrera, Dr Anastasia Ushakova
Title of project: 
Evaluating longitudinal invariance in measures of child and adolescent mental health and wellbeing across development
Proposal summary: 
Impact of research: 
The research will help inform improved measurement of mental health issues across childhood and adolescence by providing insights into how mental health manifests differently at different developmental stages as well as providing direct psychometric evidence relating to the performance of specific commonly used mental health measures. It can also enhance the use of the ALSPAC dataset by providing information on how to best use the mental health measures available to achieve scores that can be validly compared over developmental stages.
Date proposal received: 
Friday, 20 November, 2020
Date proposal approved: 
Tuesday, 1 December, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3661 - The societal costs of exposure to child maltreatment and domestic violence and abuse - 30/11/2020

B number: 
B3661
Principal applicant name: 
Kevin Herbert | Primary Care Unit, Department of Public Health & Primary Care, University of Cambridge (United Kingdom)
Co-applicants: 
Professor Steve Morris, Professor Gene Feder, Dr Annie Herbert, Dr Abigail Fraser
Title of project: 
The societal costs of exposure to child maltreatment and domestic violence and abuse
Proposal summary: 

Child maltreatment (CM) and domestic violence and abuse (DVA) are highly prevalent violations of human rights, recognised as being responsible for significant adverse short- and long-term impacts on the health, wellbeing and life opportunities of affected individuals. Multiple common risk factors are known to exist for CM and DVA, contributing to a high degree of co-occurrence. (1–3)

Understanding how these adversities interact and quantifying their individual and combined impacts is key to deriving accurate estimates of the burden that CM and DVA impose, both on services and on the individual throughout their life-course. Previous estimates of the economic burden of abuse were focused on either CM or DVA in isolation, which may fail to fully account for the intersection of CM and DVA and the relationships between exposure to multiple adverse childhood experiences and poor health. (4,5)

Study aims:
1) To estimate the impact on life outcomes (e.g. physical and mental health, healthy behaviours, employment and earnings, welfare use) resulting from exposure to CM and/or DVA, and to investigate the how this burden varies with household CM/DVA co-occurrence. This will inform parameters for the development of a multi-sectoral, incidence-based societal cost model and cost-effectiveness models for evaluation of relevant interventions.
2) To perform a comparative analysis with outcomes estimated from the Australian Longitudinal Study on Women's Health (ALSWH). (6) This will enable investigation of commonalities or differences between the UK and Australian cohorts with respect to the impact on life outcomes from exposure to abuse.

1. Herrenkohl TI, Sousa C, Tajima EA, Herrenkohl RC, Moylan CA. Intersection of Child Abuse and Children’s Exposure to Domestic Violence. Trauma, Violence, Abus. 2008;9(2):84–99.
2. Appel AE, Holden GW. The Co-Occurrence of Spouse and Physical Child Abuse: A Review and Appraisal. J Fam Psychol. 1998;12(4):578–99.
3. Edleson JL. The Overlap Between Child Maltreatment and Woman Battering. Violence Against Women [Internet]. 1999;5(2):134–54. Available from: https://doi.org/10.1177/107780129952003
4. Hughes K, Bellis MA, Hardcastle KA, Sethi D, Butchart A, Mikton C, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Heal [Internet]. 2017;2(8):e356–66. Available from: http://www.sciencedirect.com/science/article/pii/S2468266717301184
5. Bellis MA, Hughes K, Ford K, Ramos Rodriguez G, Sethi D, Passmore J. Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis. Lancet Public Heal [Internet]. 2019 Oct 1 [cited 2020 Apr 17];4(10):e517–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31492648
6. Loxton D, Dolja-Gore X, Anderson AE, Townsend N. Intimate partner violence adversely impacts health over 16 years and across generations: A longitudinal cohort study. PLoS One [Internet]. 2017;12(6):e0178138. Available from: https://doi.org/10.1371/journal.pone.0178138

Impact of research: 
The estimates derived from this study will be used to inform multi-sectoral, incidence-based cost and cost-effectiveness models to quantify the combined lifetime societal costs associated with CM and/or DVA in families, and to evaluate the cost-effectiveness of relevant interventions. The development of these models, built upon the best available evidence will enable robust comparative evaluations of alternative interventions that aim to reduce either the occurrence or severity of CM or DVA. The models will thus provide a framework upon which decision-makers can explore the impact of implementing alternative policies and identify the most cost-effective methods for addressing the consequences of CM and/or DVA. The comparative analysis of the ALSPAC and ALSWH studies will provide insight into whether the impacts of abuse are generalisable between the UK and Australian populations. The findings of these analyses will thus have implications for the approaches that the respective nations may need to take to address the impacts of abuse.
Date proposal received: 
Wednesday, 18 November, 2020
Date proposal approved: 
Monday, 30 November, 2020
Keywords: 
Health Economics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Diabetes, Mental health, Obesity, Computer simulations/modelling/algorithms, Childhood - childcare, childhood adversity

B3660 - DNA methylation indices of cancer risk factors - 24/11/2020

B number: 
B3660
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Co-applicants: 
Scott Waterfield, Dr Paul Yousefi, Professor Caroline Relton
Title of project: 
DNA methylation indices of cancer risk factors
Proposal summary: 

Cancer outcomes are improved when it is detected early. There is therefore a need for assays for identifying individuals with high cancer risk that can be applied to peripheral tissues such as blood or saliva. There is strong evidence that DNA methylation levels in these tisues encodes biomarkers for cancer risk factors such as cigarette smoke exposure, BMI, diabetes and biological aging. We plan to create DNA methyhlation models of cancer risk factors that can be combined to identify individuals with high cancer risk using peripheral blood samples.

Impact of research: 
We hope to eventually develop non-invasive tests for prioritizing individuals from the general population with higher cancer risk for further cancer screening.
Date proposal received: 
Monday, 16 November, 2020
Date proposal approved: 
Tuesday, 24 November, 2020
Keywords: 
Epidemiology, Cancer, Computer simulations/modelling/algorithms, Microarrays, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics

B3662 - Does opting in or out affect the take up of incentives in a long running population-based cohort study A nested randomised tria - 24/11/2020

B number: 
B3662
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Dr Dan Smith
Title of project: 
Does opting in or out affect the take up of incentives in a long running population-based cohort study: A nested randomised tria
Proposal summary: 

Effective strategies are critical to engage and retain participants of long term studies. A recent systematic review identified that the most common retention strategy employed was a cash/voucher incentive (59/95 studies reviewed)1. The Avon Longitudinal Study of Parents and Children has been collecting data annually from participants for over 30 years. Participants (parents and their offspring now aged ~28) are offered a £10 high street shopping voucher to complete our annual questionnaires. Across those generations we would anticipate upwards of 10,000 completed questionnaires. This comes at a substantial financial burden of over £100,000. Anecdotally, we are aware that some participants do not use their voucher once claimed or would be happy to complete regardless. The study has always provided an opt-out option for participants to indicate that they do not wish to receive their voucher, however, we were interested to see whether an opt-in option could introduce cost saving. We therefore randomised participants receiving invitations to complete the last annual questionnaire (late 2019/early 2020) to opt-out of receiving their voucher or to opt-in.

Impact of research: 
Date proposal received: 
Friday, 20 November, 2020
Date proposal approved: 
Tuesday, 24 November, 2020
Keywords: 
Epidemiology, cohort study management

B3663 - Depressive symptoms from childhood to adulthood - 24/11/2020

B number: 
B3663
Principal applicant name: 
Tamsin Jane Ford | University of Cambridge (United Kingdom)
Co-applicants: 
Mr Pascal Schlecter, Dr Sharon Neufield, Professor Paul Wilkinson
Title of project: 
Depressive symptoms from childhood to adulthood
Proposal summary: 

DDepression affects up to 300 million people worldwide and is one of the greatest causes of disability in the world. While many aspects of depression trajectories from adolescence to adulthood are well understood, depression is still among the most unreliable diagnoses of all categorical mental disorders. Additionally, changes in symptom levels across adolescence and young adulthood are as yet poorly understood. This may result from nosological conceptualizations of mental disorders that do not vary for children as compared to adolescents or adults. Only the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders describes irritability rather than depressed mood as an additional core symptom for children and adolescents. In this vein, researchers and practitioners often apply sum score models that reflect these considerations. However, these models rely on strong assumptions and we therefore aim to use Avon Longitudinal Study of Parents and Children data to investigate depressive symptoms in more depth.

Impact of research: 
This research will provide new insights into the course of depressive symptoms during adolescenc, providing useful information for both clinical research and practice about how the reporting of symptoms and their developments change, or not, over time. Specifically, these analyses will inform whether nosological conceptualizations of depression in children and adolescents are empirically justified. We will also probe the importance of parent-child discrepancies in reporting of depressive symptoms in predicting later outcomes. This may elucidate a new marker for sequelae following adolescent depression.
Date proposal received: 
Monday, 23 November, 2020
Date proposal approved: 
Tuesday, 24 November, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Computer simulations/modelling/algorithms, Development

B3659 - Effects of adolescent physical activity on physical and mental health in adulthood novel multivariate pattern analysis approach - 18/11/2020

B number: 
B3659
Principal applicant name: 
Ahmed Elhakeem | MRC IEU
Co-applicants: 
Dr Matteo Sattler
Title of project: 
Effects of adolescent physical activity on physical and mental health in adulthood: novel multivariate pattern analysis approach
Proposal summary: 

The benefits of physical activity (PA) for health are well established. However, limited evidence is available on the relative importance of specific intensities of PA as well as sedentary time for major health outcomes. In conventional analyses, accelerometer data are collapsed into only a few intensities (e.g. light, moderate-to-vigorous).This causes substantial loss of information and limits the detection of the relative importance of specific intensities. In this project we will use a novel multivariate pattern analysis approach to describe the entire PA intensity spectrum and examine the relative importance of different PA intensities on physical and mental health and mental wellbeing.

Impact of research: 
By using multivariate pattern analysis to study the the entire PA intensity spectrum and how this related to major health measures in adulthood, this study will advance our understanding how different intensities fo activity in adolescence relate to adult health.
Date proposal received: 
Friday, 13 November, 2020
Date proposal approved: 
Wednesday, 18 November, 2020
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Blood pressure, BMI, Bones (and joints), Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Metabolic - metabolism, Physical - activity, fitness, function, Statistical methods

B3652 - Genetics Adverse Childhood Experiences ACEs and Developmental and Behavioral Outcomes - 18/11/2020

B number: 
B3652
Principal applicant name: 
Hexuan Liu | University of Cincinnati (United States)
Co-applicants: 
Dr. J.C. Barnes, Dr. Joseph Nedelec, Breanna Clark
Title of project: 
Genetics, Adverse Childhood Experiences (ACEs), and Developmental and Behavioral Outcomes
Proposal summary: 

While previous research has consistently shown a relationship between adverse childhood experiences (ACEs) and developmental and behavioral outcomes later in life, understanding of mechanisms that explain the relationship is still insufficient. In particular, the role of genetics remains unknown. In this project, we propose to study how genetic factors and ACEs jointly and interactively affect individuals' developmental and behavioral outcomes, such as delinquent behavior and substance use. Specifically, we propose to examine whether and to what extent the influence of ACEs on the developmental and behavioral outcomes depends on children’s genetic susceptibility. Moreover, to what extent effects of parental genetic risk on child’s developmental and behavioral outcomes operate via ACEs.

Impact of research: 
The impact of this research will be three-folded. First, it improves our understanding of the role of genetics in research of ACEs on children’s developmental and behavioral outcomes. Second, it highlights the importance of childhood environment on children’s developmental trajectory. Finally, it provides insights to studies of intergenerational influences.
Date proposal received: 
Friday, 13 November, 2020
Date proposal approved: 
Wednesday, 18 November, 2020
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., GWAS, Childhood - childcare, childhood adversity, Development, Genomics, Genome wide association study, Offspring, Parenting

B3657 - GWAS of age of peak velocity of depressive symptoms and investigation of associated variables - 24/11/2020

B number: 
B3657
Principal applicant name: 
Kate Tilling | University of Bristol
Co-applicants: 
Miss Amy Campbell, Dr Alex Kwong, Dr Robyn Wootton, Dr Nicole Warrington, Dr Ahmed Elkaheem
Title of project: 
GWAS of age of peak velocity of depressive symptoms and investigation of associated variables
Proposal summary: 
Impact of research: 
Improved understanding of the genetic underpinnings of the development and progression of depression, which can then improve the identification of intervention targets and individuals for whom interventions would be relevant.
Date proposal received: 
Thursday, 12 November, 2020
Date proposal approved: 
Wednesday, 18 November, 2020
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Statistical methods, Sex differences

B3642 - Metabolic Health and Obesity-Relevant Diseases - 13/11/2020

B number: 
B3642
Principal applicant name: 
Marc J. Gunter | International Agency for Research on Cancer (IARC) (France)
Co-applicants: 
Dr Mary Playdon
Title of project: 
Metabolic Health and Obesity-Relevant Diseases
Proposal summary: 

Metabolic health is emerging as an important risk and prognostic factor for metabolic diseases, including cardiovascular disease (CVD), diabetes and cancer. (1-12) Metabolic health has been defined according to the presence or absence of a minimum number of cardiometabolic risk factors defined according to clinical cut-points (i.e. elevated waist circumference, triglycerides, blood pressure, and fasting glucose, low HDL-cholesterol, insulin resistance (HOMA-IR) and inflammatory biomarkers (hsCRP), or pharmacological treatment for these parameters). Obesity is associated with poor metabolic health, but metabolically unhealthy individuals may be at high risk of metabolic diseases, independent of BMI (metabolically unhealthy normal-weight phenotype, MUHNW) and obese individuals that are metabolically healthy may have similar disease risk to their lean counterparts (metabolically healthy obese phenotype, MHO). (1) Analysis of data from the US National Health and Nutrition Examination Survey showed that a substantial proportion of overweight or obese individuals are metabolically healthy and over 30% of normal weight individuals are cardiometabolically unhealthy. (13) The etiologies of the associations between these phenotypes and cardiometabolic disease risk are unclear. Recent studies have demonstrated the utility of using a metabolomics approach to explore the concepts of MUHNW and MHO in relation to cardiometabolic disease endpoints. For example, an 'obese metabolome' (metabolites related to insulin resistance, branched chain and aromatic amino acids, nucleotide metabolites, and several lipid classes) associated with a 2 to 5-fold increased risk of cardiovascular events, independent of BMI, in the TwinsUK cohort. (14) Matched for BMI, MUHNW individuals had higher visceral adiposity, higher blood pressure and were also more likely to become obese over time compared with their metabolically healthy lean counterparts. Such findings point towards the potential of metabolomics for disease risk stratification, where BMI alone can fail to identify a significant proportion of individuals that may be at risk for cardiometabolic disease. We propose to leverage the unique resources of COMETS to determine metabolites associated with metabolic health, how this profile associates with obesity-relevant diseases (i.e. obesity-related cancers and cardiovascular disease), and the extent to which metabolites mediate the association of body mass index with these outcomes.

Impact of research: 
We propose to leverage the unique resources of COMETS to determine metabolites associated with metabolic health, how this profile associates with obesity-relevant diseases (i.e. obesity-related cancers and cardiovascular disease), and the extent to which metabolites mediate the association of body mass index with these outcomes.
Date proposal received: 
Thursday, 5 November, 2020
Date proposal approved: 
Friday, 13 November, 2020
Keywords: 
Epidemiology, Diabetes, Obesity, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Metabolic - metabolism

B3653 - Birth mode impact on social behavior - 13/11/2020

B number: 
B3653
Principal applicant name: 
Will Kenkel | University of Delaware (USA)
Co-applicants: 
Title of project: 
Birth mode impact on social behavior
Proposal summary: 

This research will investigate whether birth mode shapes social behavior in childhood and adolescence. Cesarean delivery results in the newborn being exposed to lower levels of several important hormones than newborns delivered vaginally. These same hormones are known to shape social behavior throughout development, which leads us to hypothesize that birth is an important time for the developing brain. Disrupting hormonal signaling at birth via cesarean delivery is thus likely to impact the newborn's development.

Levels of each of the ‘birth signaling hormones’: oxytocin, arginine vasopressin, epinephrine, norepinephrine, and the glucocorticoids are lower following delivery by cesarean section compared to vaginal delivery, and there is substantial evidence for each of these hormones that manipulations in early life results in long-term neurodevelopmental consequences. This set of hormones has been extensively studied for their various roles in regulating social behavior in humans and non-human animals, often in a developmental context such as this, where manipulating their levels in early life alters social behavior throughout the rest of development. Furthermore, epidemiological associations have linked cesarean delivery with increased risk of autism spectrum disorder diagnosis and delayed social skills in early childhood. Finally, premature delivery is associated with markedly diminished rates of romantic attachment and sexual behavior. Thus, through multiple lines of evidence, we arrive at the central hypothesis: that birth mode can shape social behavior throughout the rest of life.

Impact of research: 
I hope that this work will yield a richer understanding of the neurodevelopmental consequences of birth mode. The next step for my research will be to experimentally explore these questions in a rodent model.
Date proposal received: 
Friday, 6 November, 2020
Date proposal approved: 
Friday, 13 November, 2020
Keywords: 
Endocrinology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Childhood - childcare, childhood adversity, Development, Equipment - MRI, Mothers - maternal age, menopause, obstetrics, Puberty

B3651 - Microbiome transfer and intergenerational transmission of mental health - 09/11/2020

B number: 
B3651
Principal applicant name: 
Sam Cartwright-Hatton | university of sussex (United Kingdom)
Co-applicants: 
Abigail Thomson, Dr Kathryn Lester
Title of project: 
Microbiome transfer and intergenerational transmission of mental health
Proposal summary: 

Mental health problems run in families. This arises from a range of genetic and environmental factors.

Recently, we have seen the impact that the human microbiome has on physical health (e.g inflammatory bowel disease, asthma, obesity) and mental health (depression, anxiety, autism).

Like mental health, the microbiome also runs in families, likely because of environmental transfer of microbiota between family members and, in particular, the seeding of the neonatal microbiome during the birth process. We wondered whether the sharing of microbiomes within families may partially explain familial similarities in mental health.

It is not possible to conduct an experiment, interrupting the transfer of microbiota from mother to child, to see if this had an impact on transfer of intergenerational risk for mental health problems. However, nature (helped along by NHS maternity services) provides us with a natural experiment: Approximately 20-25% of births are via caesarean section, and there is mounting evidence that this results in substantially lower mother-child microbiome transfer than vaginal birth. This microbiome transfer process can be further interrupted by other factors, including prenatal/perinatal antibiotic use and breastfeeding practices.

This study will explore the impact of early-life microbiome transfer on the intergenerational transmission of mental health problems.

Impact of research: 
To our knowledge, this research will be the first to offer an insight into the mental health impacts of disrupted microbiome colonisation at birth. More particularly, it will allow us to explore the role of the intergenerational transmission of microbiome on the intergenerational transmission of mental health - a potential new mechanism through which risk factors for child mental health are forged.
Date proposal received: 
Friday, 6 November, 2020
Date proposal approved: 
Monday, 9 November, 2020
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Microbiome

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