Proposal summaries
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.
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.
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.
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.
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.
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.
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
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.
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.
B3339 - Summary statistics from metabolomics data - 09/07/2019
B3337 - Neighbourhood deprivation child conduct problems and adolescent delinquency - 24/07/2019
Many adults in the United Kingdom suffer from psychological distress. Psychological distress can range from worrying a lot, to feeling down, to even more serious problems. Importantly, existing research suggests that adults with psychological difficulties often also have behavioural problems as children. Understanding how psychological distress develops is a crucial first step in helping us (i) identify which children are most at risk and (ii) develop targeted strategies to prevent or manage such problems. The reasoning here is that if we can prevent the development of psychological distress in childhood, these children will be less likely to show psychological distress as adults.
We already know that children who show conduct problems (e.g. fighting, lying, stealing) tend to come from riskier circumstances. For example, these children can have mothers with psychological difficulties. Moreover, mothers that have psychological difficulties tend to live in deprived neighbourhoods (e.g. poverty, crime, pollution, low access to greenspace such as parks with trees and grass). Here, the idea is that neighbourhood deprivation can associate with maternal psychological difficulties and family dysfunction, which in turn, can lead to less consistent, stimulating and more punitive parenting behaviours, and poorer child behavioural outcomes. However, characteristic of the parent(s), such as education, employment and psychological distress can play a role in the type of neighbourhood a child grows up in. These characteristics can also affect how vulnerable a parent is to stress-inducing features of the neighbourhood, and therefore could potentially affect the type of parenting used on a child.
During adolescence, youth spend less time with their families and more time âhanging outâ with their peer groups (or friends). Therefore, youth are more directly exposed to the neighbourhood, including both structural (e.g. poverty, pollution, distance from green space) and social (crime and deviant peers) deprivation factors. Similar to the mothers, individual characteristics of a teenager can increase the likelihood that individual will be exposed to risk factors in the neighbourhood. Here, impulsivity (i.e., acting without thinking, thrill seeking) can influence the type of social environments for which an adolescent actively seeks out. Indeed, high impulsivity can lead to affiliation with other teenagers who are engaging in delinquent behaviours (e.g. fighting, lying, stealing), which in turn, can increase a teenagerâs substance use, unsafe sexual activity and criminal behaviours. Thus, during adolescence, the individual characteristics of youth may associate with risk-related behaviours within the neighbourhood context.
To date, however, existing studies have not teased out the specific biological mechanisms that could explain how neighbourhood deprivation might relate to punitive parenting for the mother, or to a teenager âhangingâ out with a deviant peer group. One potentially important biological factor of this kind is a âpolygenic scoreâ. A polygenic score gives you a genetic risk for some type of trait (e.g. depression, thrill seeking) or disease (e.g. cancer). These scores are based very large studies, sometimes over 1 million people, that show associations between traits or disease with genetic variants across the entire known genome. These different variants and then summed into a single âpolygenic scoreâ in smaller, independent studies.
In this study we plan to address two key potential limitations of existing research: (1) Existing studies have not examined how maternal polygenic risk for depression can affect harsh parenting and child conduct problems, particularly if living within high neighbourhood deprivation. (2) Existing studies have not assessed adolescent polygenic risk for externalising problems and impulsivity (e.g. ADHD, sensation seeking) associates with higher affiliation deviant peer affiliation, particularly if living within high neighbourhood deprivation.
This study will address each of these main limitations of the existing research. We are ideally placed to achieve these aims as we have access to psychological, parenting, behavioural, friendship and genetic data already collected from two very large scale samples of children, extensively studied from childhood and into adolescence (The Avon Longitudinal Study of Parents and Children, in Southwest England and Generation R, Rotterdam, The Netherlands).
We hope that results from this research will help answer questions around why some caregivers are more likely to use punitive parenting, and why children are more likely to have conduct problems, and guide early intervention for high-risk children who may be prone to impulsive and thrill seeking behaviours.
B3338 - Psychiatric outcomes of sexual assault - 07/08/2019
Sexual assault (SA) is a key risk factor for the development of post-traumatic stress disorder (PTSD) and other psychiatric disorders. However, despite the ubiquity of sexual assault, many individuals do not develop any PTSD or other psychiatric disorders. Predicting which individuals may be at higher risk of PTSD, and identifying clinical and biological factors that lead to resilience or disease risk will be vital to developing new treatments and therapies, and in matching patients to appropriate, timely interventions. We propose to use environmental, genetic and methylation data from the ALSPAC cohort, to identify the key factors influencing psychiatric disease risk and resilience after sexual assault.
B3336 - CoCo90s biobank views of donors - 04/07/2019
Research on cord blood and placenta can be used to develop treatments for conditions that affect pregnancy and can hopefully lead to improvements in childrenâs health. A large-scale research study in the UK collected over 4,000 umbilical cord samples and over 8,000 placentas from mothers and children in the 1990s. These children have now grown to adulthood and are donating cord blood and placentas from their own pregnancies (or those of their partners) to the research study. This project will investigate how this multi-generational collection of materials collected from birth is viewed by mothers and fathers in the study and by scientists involved in creating and maintaining the collection. This research will enable a better understanding of what donors and research scientists think about cord blood and placenta and the methods for studying and preserving it.
B3335 - Changing causes and consequences of overweight obesity and underweight a historical comparison of UK and Norwegian cohorts 19 - 27/06/2019
Since the 1980s overweight and obesity have increased dramatically, but we do not know if this has altered their health and social consequences for individuals. In high-income countries, inequalities in underweight is largely ignored, but my research on body weight and unemployment suggests they are greater than realised. Weight misperception (failure to recognise oneâs overweight/obesity) has increased, but the implications for individual health and health inequalities are unclear.Â
Using UK and Norwegian data from 1984-2021, I will:Â
Extend knowledge of economic inequalities in underweight in adults and children Â
Investigate influence of overweight/obesity on depression, depression on overweight/obesity, and whether relationships have changed with timeÂ
Investigate consequences of weight misperception for weight, mental health, and health inequalitiesÂ
Results will identify high-risk groups for underweight and illuminate causes, explore societal factors modifying body weight-depression links, indicate mental health returns to tackling obesity, and inform effective weight management strategies which also support wellbeing.
B3333 - The Genetic Basis of Developmental Coordination Disorder - 25/06/2019
Five percent of school age children have developmental coordination disorder (DCD). People with DCD find tasks such as throwing a ball, writing, or brushing their teeth extremely difficult, and are more likely to struggle academically even though they are just as smart. Despite being extremely common, we understand little of why some children get DCD.
We know that sometimes DCD can run in families but we don't understand the causes of this. This study will be the first to look for these inherited causes. We will use genetic data from the ALSPAC cohort to find genes that are underlying DCD. This will help us to understand how these genes affect the pathways that are required in a developing brain.
We will also use this genetic information to help us understand why some children go on to develop other difficulties like ADHD or language problems, whereas other children do not. We can look into how these behaviours interact with the movement and planning difficulties seen in DCD, and whether they are important in the development of these behaviours in typically developing children.
B3320 - Gene-environment interplay psychosocial factors and cognition in post-bereavement psychopathology - 25/06/2019
Over 75% of all adolescents will experience the death of a close friend by the time they reach college age, and 3 million children will experience the death of a parent by the age of 18 (or the equivalent of one child in every classroom). Bereavement is associated with increased risk for psychopathology, even though available clinical trial data suggest that interventions are effective. Extending these early clinical trial findings to children and adolescents is hampered by the limited understanding of temporal patterns of post-loss psychopathology, as well as the joint effects of genetic liability, developmental timing, cognitive ability, psychosocial variables, and environmental exposures. This project will focus on addressing these knowledge gaps by investigating pathogenic processes in post-exposure psychopathology among youth, ultimately pointing to candidate preventative and intervention approaches.