Proposal summaries
B3674 - Childcare attendance and age of introductions on respiratory infections allergy and asthma - 15/12/2020
Studies examining the effects of attendance at childcare on the development of asthma are conflicting. There are studies that report a protective effect, no effect and an increased risk of respiratory symptoms and allergic disease. Risks associated with asthma are however influenced by age of childcare attendance and family history of asthma. Children attending childcare also have more frequent infections than those who stay at home, and infections are a known risk factor for asthma. This study aims to investigate if attendance at childcare is associated with increased risk of allergies and asthma, and if the age of introduction and respiratory infections play a role.
B3675 - Myopia in Young Adults - 15/12/2020
Myopia (short-sightedness) is an eye condition in which distance vision is blurry. People with myopia need to wear glasses or contact lenses, or have laser refractive surgery, to achieve sharp distance vision. When people with myopia get older, they are at a higher-than-average risk of developing permanent sight problems such as macular disease. Myopia typically develops during school age. The reason it develops is not understood, however both genes and lifestyle factors are known to play a role. Children whose parents have myopia inherit a genetic predisposition to develop myopia themselves. In clinical studies, children who are randomly assigned to spend extra time outdoors each day have a lower incidence of myopia, suggesting that spending too little time outdoors is a risk factor. Individuals who spend more years at school also tend to develop a higher level of myopia. Around the world, the prevalence rate of myopia varies widely. This is thought to be related to the variation in the ‘intensity’ of school work and the pressure to do well at school. Myopia has also been linked to mental health problems such as depression and to levels of physical activity. However, for most of these links, it is unclear if myopia is a cause or a consequence of the association.
The ALSPAC cohort is unique in the scale and breadth of the information that has been collected about vision problems in childhood. This includes information about myopia development. In previous studies of ALSPAC participants, our research group has documented the time-course of myopia development and exposure to risk factors or protective factors such as time spent outdoors. For example, children from the ALSPAC cohort who spent relatively less time outdoors than their peers at age 7-years-old were found to have an increased risk of developing myopia by the age of 15. Here, we propose to build on our previous findings. Our primary aim is to discover if myopia is the cause or consequence of its associations with other lifestyle factors and health or wellbeing characteristics. To do this, we will use a technique called Mendelian randomisation, which uses random inheritance of subtle genetic features in a way similar to randomisation of participants in a clinical trial. Usually, Mendelian randomisation studies require very large cohorts of participants – larger than the ALSPAC cohort. However, myopia and many of the related conditions we plan to investigate are highly heritable, which means there is a good prospect of successfully answering our research questions using data collected in a sample the size of the ALSPAC cohort. Our secondary aims are extensions of the primary aim. We will compare the eye characteristics and lifestyle of children growing up in the UK with those of children elsewhere, to investigate if the risks for myopia are similar or different in countries with high or low prevalence rates of myopia. We will also extend our previous studies into the genetics of myopia. The exceptionally high level of detail that the ALSPAC research team has collected about genetics will allow us to test the role of specific genes in conferring a predisposition to myopia, and how this varies depending on the lifestyle risk factors that children are exposed to.
B3671 - Urban exposome during pregnancy and early childhood and child cognitive and motor function - 15/12/2020
B3673 - Maternal exposure to urban environmental stressors and depression in the postnatal period - 09/12/2020
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.
B3667 - Predicting pubertal timing in boys and girls using clinical data and polygenic risk scores - 02/12/2020
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.
B3668 - The relationship between parenting and mental health the role of genetic nurture and child evocative effects across contexts - 02/12/2020
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.
B3665 - Early life exposure to cardiovascular risk factors and cerebral structure and function in young adults - 02/12/2020
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.
B3670 - National Core Studies ARQ7 Investigating the socio-economic impact of COVID-19 - 02/12/2020
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.
B3669 - Exploring epigenetic and phenotypic associations with genetic liability to juvenile idiopathic arthritis - 02/12/2020
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.
B3666 - Characterisation determinants mechanisms and consequences of long COVID providing the evidence base for health care services - 14/04/2021
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.
B3658 - Evaluating longitudinal invariance in measures of child and adolescent mental health and wellbeing across development - 01/12/2020
B3661 - The societal costs of exposure to child maltreatment and domestic violence and abuse - 30/11/2020
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
B3660 - DNA methylation indices of cancer risk factors - 24/11/2020
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.
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
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.
B3663 - Depressive symptoms from childhood to adulthood - 24/11/2020
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.
B3659 - Effects of adolescent physical activity on physical and mental health in adulthood novel multivariate pattern analysis approach - 18/11/2020
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.
B3652 - Genetics Adverse Childhood Experiences ACEs and Developmental and Behavioral Outcomes - 18/11/2020
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.
B3657 - GWAS of age of peak velocity of depressive symptoms and investigation of associated variables - 24/11/2020
B3642 - Metabolic Health and Obesity-Relevant Diseases - 13/11/2020
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.
B3653 - Birth mode impact on social behavior - 13/11/2020
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.