Proposal summaries
B3359 - Predicting adult height among children with idiopathic short stature using a polygenic risk score - 19/08/2019
Children with idiopathic short stature (ISS) are defined by height below 2 standard deviations (SD) of the mean for age and sex without any endocrine, metabolic or other disease explaining the short stature. The US Food and Drug Administration approves growth hormone (GH) treatment on children shorter than 2.25 SD of the mean for age and sex with a predicted adult height below the normal range. Given that stature in a population follows a Gaussian distribution, 2.3% of children will always be shorter than 2 SD below the mean for age and sex. However, a proportion of these children defined in childhood as having ISS will eventually achieve a normal adult height or a normal height in their families, even in the absence of expensive GH treatment.
Human height has a highly polygenic nature. It has been estimated that about 80% of variation in height can be attributed to genetics. Polygenic scores 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 height.
Therefore, we posit that a polygenic risk score for adult height may be able to effectively predict which children diagnosed as having ISS are likely to achieve a normal adult height where indication of GH treatment would not be necessary.
B3358 - Trajectories of hearing and cognitive function through the lifecourse in the Avon Longitudinal Study of Parents and Children - 30/08/2019
Loss of hearing is common, and tends to increase over the life course, affecting over 10 million people in the UK. Although there have been many studies concerning deafness in childhood, very few have examined the normal course and variation in hearing in a large population of individuals from an early age into mid and older adulthood. This is troubling since even low levels of hearing loss can result in failure to hear speech clearly, and can impact social communication, mental health and employment. Moreover hearing loss is associated with cognitive decline, and has been identified as one of the nine modifiable risk factors in the Lancet Commission on Dementia. It is not known whether hearing loss is a causal factor for cognitive decline, or a non-causal feature associated with ageing and neurodegeneration. Monitoring hearing in a population from early in life, and using novel genetic methods to investigate causality, may be crucial to understanding not just the role of hearing in cognitive function, but also the ageing process in general.
Utilising the Avon Longitudinal Study of Parents and Children (ALSPAC), this project will be the first to study, in depth, the changes in hearing ability over the life-course from early childhood to age 30 and to examine the relationship with cognitive function.
Firstly we will analyse data from approximately 5000 individuals, for whom we have detailed measures of hearing function at ages 7, 9, 11 and 14, and which we will collect again when they are age 30. We will characterise how their hearing has changed from age 7 to age 30, and identify those with who have experienced a drop in hearing ability. We will examine whether changes in hearing are associated with environmental exposures or the presence of particular genes.
Secondly we will analyse their cognitive function, using measures of memory, attention and processing speed collected at age 8, 10, 13, 15 and 24, and which we will collect again at age 30. We will compare trajectories in hearing ability with trajectories of cognitive function from age 7 to age 30, and test whether those who experience a decrease in their hearing ability are more likely to have poorer processing speed, attention and working memory at age 30.
The project is unique in that:
⢠it will provide observational information on the natural history and genetic influences on hearing over the first 30 years of life
⢠it will be the first to assess age-related relationships between changes in hearing and features of cognition through childhood into early adulthood
The information collected will be valuable for studies of further ageing of this population as well as identifying possible mechanisms linking hearing and cognition.
B3357 - Pubertal development and the gender gap in education A study using the ALSPAC birth cohort - 16/08/2019
Educational attainment and achievement has increased significantly among both men and women in industrialised countries over many years. At the same time, an increasing gender gap in education has developed in favour of women (OECD, 2015). The gender gap in education now represents a societal challenge in many industrialised countries. The causes are not known and under-researched, and there has been limited attention to potential policies for decreasing the gap.
Girls enter puberty earlier than boys, and by age 15 to 16 the gender difference in maturity reaches a peak (Mustanski et al, 2004). At this age, adolescents graduate from lower secondary education and in many European countries (including the UK and in the Nordic region), it coincides with important decisions regarding their future. The opportunities available to individuals depend heavily on their grade scores from lower secondary school. An important question to ask is therefore whether and to what extent the âbiological head startâ of girls explains their educational outperformance of boys.
B3353 - Understanding determinants of Telomere length in early life and its effect on Cardiovascular risk throughout the life course - 16/08/2019
Telomere length (TL) is a DNA marker of biological age in humans. Shorter TL (signifying older biological age) associates with higher risk of age-related disease such as coronary artery disease. Whilst TL is strongly heritable, it is also associated with lifestyle and environmental factors, such as diet, exercise and smoking in adults. However, recent studies have proposed that TL is "set" in early life and that environmental/lifestyle exposures may have more effect on TL during childhood. For example, adult smokers have, on average, shorter TL than non-smokers but smoking does not increase TL loss over time in adulthood. Therefore, the relationship between smoking and TL is more complex and is likely established at an early age. One possible explanation is that childhood exposure to smoke from parental smoking both shortens TL in the child and increases the likelihood of them smoking in later life. These same relationships may also be seen for other traits such as diet and exercise, traits that in adults are often influenced by childhood experience. Currently there are few studies that are able to address such questions. By measuring TL in children and young adults at large scale (minimum 2,900 per age group, 7, 17 and 24 years) we can more accurately explore the relationships between lifestyle and environment in childhood with TL. This will provide important information about how TL is influenced in early life and how early life exposures influence disease risk in adulthood through a biological ageing mechanism.
B3352 - Protective factors in the association between exposure to domestic violence in childhood and internalising symptoms - 12/08/2019
Childhood exposure to domestic violence is associated with long-term impairment such as increased risk of mental health illness, aggression, anti-social behaviour and poorer academic attainment, yet some children function well despite this adversity. As part of my doctoral thesis, I propose to use ALSPAC to identify the key factors which protect children and adolescentsâ mental health following exposure to domestic violence. I will also examine whether or not the protective effect of these factors vary by socio-demographic and contextual factors (i.e. age, gender, socio-economic status, and severity/duration of domestic violence).
Resilience is the ability to bounce back and successfully adapt to challenging circumstances. It is not a personality trait and is amenable to change. Individual, family, and community protective factors that promote resilience in the face of childhood adversity have been identified within the literature . Studies that have explored protective factors within the contexts of domestic violence exposure and mental health outcomes have tended to explore single factors on their own, have not considered the complexity of the issue or contribution of other adversities, and have not necessarily considered the severity of the violence witnessed. Additionally, the vast majority of all research in the field has been conducted in the USA where attitudes towards violence and outcomes for both parents and children may differ to the UK. Therefore, more evidence is needed to identify how these factors protect against mental disorders in children who have been exposed to domestic violence. This research will provide an understanding of protective factors and their effects in different contexts will provide better information for the development of targeted interventions aimed at improving the mental health of children exposed to domestic violence. Furthermore, identifying whether these protective factors only buffer against poor mental health under certain conditions will help us determine whether such interventions should be tailored to children and young people based on their characteristics and trauma exposure.
Alongside this, we would like to identify whether these factors (if any), protecting children and adolescents from internalising symptoms, are specific to the contexts of domestic violence exposure and mental health or whether they may be protective against other behavioural problems and in the context of exposure to other adverse childhood experiences such as parental alcohol/substance abuse, parental mental health problems, direct child abuse and neglect. This will also inform the potential scope of future interventions.
B3354 - Understanding the evolution of joint hypermobility pain and associated symptoms a novel multigenerational longitudinal cohort - 22/08/2019
B3356 - GWAS of breast density - 09/08/2019
Increased breast density is strongly associated with increased breast cancer risk, however, the underlying biology is unclear.
We aim to identify genetic variation associated with breast density to help explain this association.
B3355 - Anorexia and subsequent smoking cause or correlation - 09/08/2019
Smoking prevalence is reported to be increased in populations with anorexia nervosa (AN), and engagement in smoking in AN is suggested to result from attempts to control weight. However, both smoking and AN have also been linked with earlier anxiety; thus anxiety may explain the association between smoking and AN. This study will assess the prospective association between AN and subsequent smoking, across three longitudinal waves of data. Models will be adjusted for childhood worry (a symptom central to anxiety disorders), to determine whether AN explains smoking beyond the predictive effects of anxiety pathology.
B3348 - Testing a model of whether early non-specific symptoms independently predict unhealthy lifestyle behaviours and psychosis - 06/08/2019
Psychosis refers to the experience of hallucinations and/or delusions. Psychotic experiences range from short-lived symptoms that are not fully believed through to persistent severe symptoms that characterise psychotic illnesses as schizophrenia. It is well established that enduring psychotic illnesses such as schizophrenia have worse physical health than the general population, and are at an increased risk of developing long-term physical health conditions such as diabetes and heart disease. This may be due to unhealthy lifestyle behaviours, such as a lack of physical activity and smoking. Such risk factors begin early in first-episode psychosis and even before the first episode. However, the causal relationship between poor physical health and psychosis is not fully understood. We think poor physical health and psychosis may occur independently of each other, but are both related to earlier more common mental health difficulties, such as depression and anxiety.
Not everyone who experiences mental health difficulties will go on to develop psychosis or physical health problems. For those who do, recovery is possible. Medication and supportive relationships are known to help with recovery, however less is known about the role of romantic relationships specifically.
This research project aims to explore how these factors interact over time within the ALSPAC dataset.
B3350 - The Heart-Brain Connection in ALSPAC30 Cardioaggression or Neuroselection - 08/08/2019
In our ageing population the burden of both heart failure (HF) and dementia is increasing. To date there is no proven preventative or curative treatment for cognitive decline and the associated social and economic cost is huge. Both conditions share common risk factors, yet there is growing evidence of a direct relationship between the function of the heart and the brain. But we still don't know if poor cognition is a consequence or a cause of poorer cardiac function. Several aspects of this association require thorough investigation. We propose that there is a bidirectional association between cognition and cardiovascular disease (CVD) and by applying sophisticated techniques to assess cardiac and brain structure and function, this investigation will significantly advance our understanding of the causal mechanisms underlying both cardiac and cognitive decline.
B3351 - Broad Antisocial Behavior Consortium BroadABC - meta-analysis of antisocial phenotypes - 05/08/2019
The BroadABC has been created to combine the results of multiple genome-wide association studies of broad antisocial behavior (measured by symptom counts of antisocial personality disorder, ratings of aggression, conduct problems, delinquency, psychopathic personality etc) in meta-analyses in order to increase the probability of detection of genetic variants associated with individual differences in liability to antisocial behaviors. For phase 2 our aim is to include at least ~150,000 individuals.
B3349 - Simulated ALSPAC data as a resource for longitudinal research and teaching - 05/08/2019
The Avon Longitudinal Study of Parents and Children (ALSPAC) is a unique resource with a wealth of rich longitudinal data. Furthermore, ALSPAC is one of the few longitudinal cohorts with repeated assessments of self report psychiatric traits, along with a host of early exposures and later outcomes. As such, ALSPAC is a vital tool for exploring the longitudinal nature of psychiatric traits, their antecedents and later consequences.
Examining the nature of psychiatric disorders such as depression is complex and often requires advanced statistical methods to untangle complex associations and underlying mechanisms. Currently, there are few open access datasets with enough detail available for researchers to learn these complex statistical methods. As such, many researchers are forced to use datasets that do not capture the complexity of traits such as depression, and this could hinder the ability to make further progress in uncovering diseases like depression.
Given the sensitivity of the ALSPAC study, it is not appropriate to release full versions of the data. However, it is possible to simulate parts of the ALSPAC data to give the same properties, without the risk of disclosure and identification of participants.
Simulating ALSPAC data that matches the original properties of the data would provide an excellent resource for teaching purposes as well as providing an introduction to researchers wanting to use the original ALSPAC study.
B3347 - Preterm birth and health across the life-course - 31/07/2019
Survival of people born prematurely (defined as <37 weeks of gestation) has improved over recent decades due to improvements in ante and postnatal care. The long-term health consequences of being born early are only just coming to light. Here we propose to study the health outcomes of participants born prematurely compared to those born at term, with a particular focus on growth, cardiometabolic and reproductive health.
B3346 - GWAS of breastfeeding patterns - 25/07/2019
Breastfeeding isâ¯life-savingâ¯for some vulnerable populations (egâ¯poor sanitation contexts) and individual babies (egâ¯preterm),â¯however breastfeedingâ¯accordingâ¯to WHO guidelinesâ¯remains rareâ¯in the UK andâ¯other high-income countries. Other than the obvious lack of support for new mothers starting their breastfeeding journey, little is known about individual barriers to breastfeeding, some of which could be specific to the mother, and some could be specific to the baby.
This project aims to understand to what extent the mother and baby's genetic make up can influence the pair's chances of starting and sustaining breastfeeding.
This knowledge will help in several ways, and specifically:
1. it will allow researchers to conduct robust studies into the health effects of breastfeeding for mothers and babies,
2. it will shed light onto needs and approaches that could be used to help support breastfeeding.
B3345 - Experiences of taking part in cohort studies - 02/08/2019
The UK supports an unparalleled collection of large-scale population cohorts which have provided a wealth of longitudinal biological and social data for studying health and wellbeing throughout the lifecourse. The MRCâs 2014 Cohort Strategic review estimated a significant proportion of the UK population has participated in cohort studies. Estimates suggest that 2.5m have taken part, and currently around 2.2m people (3.5% of the population) are cohort members. However, participantsâ experiences of taking part in cohort studies, and their attitudes towards the research that they are participating in, are relatively un-studied. What research there has been identified key issues around participation, information and consent.
This new research project seeks to build on previous work undertaken by the Health Experiences Research Group, in the Nuffield Department of Primary Care Health Sciences (HERG), on experiences of taking part in research. Previous studies have included experiences of taking part in clinical trials, biobanking and genomic research, all published as modules on Healthtalk.org (http://healthtalk.org/peoples-experiences/medical-research). In an era of rapid developments at the frontiers of medicine and technology, are our attitudes to personal data, data sharing and medical research changing? We seek to explore cohort participantsâ views and experiences. Our aims with this new research project are to record the experiences of people who take part in cohort studies in the UK, to understand the motivations of people who agree to take part, their experience of receiving information, giving consent and participating, their attitudes to data sharing and their views about receiving results vis a vis confidentiality. This research will gather suggestions for improving recruiting and retention of participants and develop a web-based resource, published at Healthtalk.org, for other people invited to take part in cohort studies where they can find out more about what it is like to take part.
B3343 - Reproductive health questions in G0 - 31/07/2019
The last ALSPAC mothers (G0) questionnaire was in 2013. A subset of mothers attended the last FoM4 clinic in 2014-5.
Here we are proposing to collect up-to-date information about women's reproductive health, with a particular focus on the menopausal transition.
B3344 - Determinants and correlates of depression in women in later middle age - 31/07/2019
B3342 - Children born prematurely entering school a year early a double disadvantage - 22/07/2019
Previous studies, including those using ALSPAC data, have found that children who are born prematurely are at risk of poorer educational outcomes than their peers. They have also found that summer-born children in England, who are the youngest in their school year, do worse than children born at other times of year. School entry in England is based on chronological age, and so it has been hypothesised that children who are born early and in the summer months may be 'doubly disadvantaged' as they are both premature and start school a year earlier than they would have had they been born at term.
Recent research by researchers using Born in Bradford data found evidence of this 'double disadvantage': children who were born pre-term and who started school a year earlier than they should have had they been born at term, were less likely to have a 'Good Level of Development' at age 5 years than their peers who were summer born but not pre-term, or who were pre-term but started school within the same school year as they would have had they not been premature.
Our proposed project using ALSPAC data will aim to replicate and extend the Born in Bradford findings.
B3341 - Maternal and paternal stress during pregnancy and offspring body composition and cardiometabolic health - 11/07/2019
Stress experienced by parents during pregnancy and up to two years after the baby is born can have negative consequences for the mother and the child. The time from pregnancy up until about two years after the birth (also known as the 'first 1000 days') is a sensitive period during which (expectant) parents can experience high stress and anxiety, and during which children are at greater cardiometabolic risk. There is little research examining effects of maternal stress and anxiety on child cardiometabolic outcomes, with even less research examining effects of paternal stress and anxiety.
B3340 - Integration of body fat and lean mass loci reveals genetic clusters with distinct cardiometabolic effects - 08/07/2019
Through a large international collaboration, we identified more than a thousand genetic factors that are associated with how much of a personâs weight is fat mass and how much is lean mass. We subdivided these genetic factors into six groups based on how they affect multiple aspects of body size, composition and shape (e.g., body mass index, height, waist-to-hip circumference). These six clusters of genetic factors each have distinct effects on obesity-related diseases, such as type 2 diabetes and cardiovascular disease. In addition, we found that the clusters also had differential effects on body size at birth and in childhood. We would like to use the data from the ALSPAC study to investigate if these six groups of genetic factors affect trajectories of body size and composition throughout the development of a child, from birth until early adulthood.