Proposal summaries
B3265 - Development of a widely applicable tool for phenome scans and data processing - 26/03/2019
While studies examining the effect of an exposure of interest on specific health issues provides important understanding into the determinants of health and disease, it would be arguably more useful to determine, in a single study, the extent that the exposure affects a very large number of health-related traits and diseases. Phenome scans are a particular type of 'hypothesis-free' study, that test the association of a trait of interest with a comprehensive array of phenotypes â the âphenomeâ. They can be used with an approach called Mendelian randomization to search for the causal effects of a trait of interest with potentially many outcomes. Performing a phenome scan is typically non-trivial as the set of phenotypes available in a cohort tends to be highly heterogeneous. Recently, we developed a tool called PHESANT, that allows researchers to conduct phenome scans in UK Biobank. However, currently it is not easy to perform phenome scans in ALSPAC. In this project we will develop innovative software that enables researchers to easily perform their own comprehensive phenome scans in ALSPAC, searching across 'all' phenotypes is this cohort. We will demonstrate this software by searching for the causal effects of education, as an exemplar.
B3267 - Offspring adaptation to social isolation Testing a novel prenatal social environment adaptation hypothesis - 05/03/2019
B3263 - Shared genetic pathways influencing normal/abnormal facial shape medical conditions - an international collaboration - 09/04/2019
Historically, craniofacial genetic research has understandably focused on identifying the causes of craniofacial anomalies and it has only been within the last 10 years, that there has been a drive to detail the biological basis of normal-range facial variation. This initiative has been facilitated by the availability of low-cost hi-resolution three-dimensional systems which have the ability to capture the facial details of thousands of individuals quickly and accurately. Simultaneous advances in genotyping technology have enabled the exploration of genetic influences on facial phenotypes, both in the present day and across human history. There are several important reasons for exploring the genetics of normal-range variation in facial morphology.
- Disentangling the environmental factors and relative parental biological contributions to heritable traits can help to answer the age-old question âwhy we look the way that we do?â
- Understanding the aetiology of craniofacial anomalies; e.g., unaffected family members of individuals with non-syndromic cleft lip/palate (nsCL/P) have been shown to differ in terms of normal-range facial variation to the general population suggesting an etiological link between facial morphology and nsCL/P.
- Many factors such as ancestry, sex, eye/hair colour as well as distinctive facial features (such as, shape of the chin, cheeks, eyes, forehead, lips, and nose) can be identified or estimated using an individualâs genetic data, with potential applications in healthcare and forensics.
- Improved understanding of historical selection and adaptation relating to facial phenotypes, for example, skin pigmentation and geographical latitude.
- Highlighting what is known about shared facial traits, medical conditions and genes.
This project will be an advancement on a previous studies undertaken at 15 years of age which has yielded a series of landmark articles. The 15 year old cohort will be recalled at 30 and 3D facial images will be collected for as many of the original 4747 15 year old faces as well as their mothers/fathers and their own offspring.
The computer generated 3D facial images/shells will be important in exploring:
- the link between normal variation and craniofacial anomalies
- heritability of facial features (e.g. overall face size/shape and local features nose, lips chin etc)
- Environmental and shared genetic influences on facial shape and reported medical conditions
- Facial ageing from 15 to 30 years of age
- Forensic science relating to identification of facial types from genetic data
- Engagement of the ALSPAC family in deriving relatedness in parents and offspring
- Enable the research team to lead and collaborate with other international cohort studies/cleft lip and palate/craniofacial anomalies/normal facial variation and shared genetic consortia.
There has been significant progress in the first 6 years of GWAS and facial genetics. With increased sample sizes, improved understanding of shared genetic influences on human traits and advancement in techniques there is likely to be significant further progress in the next 6 years. Understanding the face will explain âwhy we look the way we doâ a range of normality and abnormality that
will be useful in a large number of healthcare applications and forensic science.
B3264 - The continuation of interpersonal violence Investigation into the relationship between bullying and intimate partner violence - 26/02/2019
It is well documented within academic and public policy literature that exposure to violence in all its forms has a detrimental impact on the well-being of all those involved, and is thus a serious public health issue. In particular, attention has been directed towards bullying and intimate partner violence (IPV) as these are two of the most common forms of violence perpetrated and experienced. Individuals who are involved in bullying or IPV as either perpetrators or victims are at an increased risk of experiencing mental health problems (i.e. depression, anxiety, substance use) and greater difficulties in life (i.e. academic decline, financial difficulties, poor physical health). To date the majority of research has investigated bullying and IPV independently of one another in the same individual. The small number of studies which have not, have found that bullying perpetrators are more likely to be perpetrators of IPV and victims of bullying are more likely to be victims of IPV. However these studies have predominantly been conducted in America, have focused on teen dating violence as a form of IPV and have investigated the relationship concurrently. Furthermore very few studies have investigated the continuation of exposure to violence from bullying to IPV by exploring underlying mechanisms which may explain why this is happening for some and not all. As bullying and IPV are interpersonal in nature, factors which influence social interactions and the processing of the social environment and cues may help us to understand the relationship between the two. For example these include the ability to correctly identify emotions and the causes of events and interactions. Identifying individuals who experience both forms of violence and thus experience violence across their lifespan could prove to be an important way to predict and improve the impact on their well-being.
B3262 - The association between pregnancy and change in cardiovascular health - 22/02/2019
It is currently unknown if and what effect pregnancy has on cardiac structure and function.
B3259 - The EWAS Catalog a database of epigenome-wide association studies - 19/02/2019
DNA methylation is the process of adding a methyl group to a DNA molecule, often changing how the molecule interacts with other cellular factors. Methylation mainly occurs at cytosines in humans, often in the context of a cytosine followed by a guanine (CpG). Epigenome-wide association studies (EWAS) seek to understand the link between DNA methylation patterns at thousands or millions of CpG sites across the genome to various traits and exposures. In recent years, the increase in availability of DNA methylation measures in population-based cohorts and case-control studies has resulted in a dramatic increase in the number of EWAS being performed and published. To make this rich source of molecular data more accessible, we have manually curated a database of CpG-trait associations (with p<1x10-4) from published EWAS, each assaying over 100,000 CpGs in at least 100 individuals. The database currently contains over 500,000 CpG associations for more than 150 EWAS. It is accompanied by a web-based tool and R package that allow these associations to be easily queried. In the near future, we hope this database will be extended to include genome-wide EWAS summary statistics, including over 200 million associations from over 500 EWAS of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N~900). This database will give researchers the opportunity to quickly and easily query EWAS associations to gain insight into the molecular underpinnings of disease as well as the impact of traits and exposures on the DNA methylome. The EWAS Catalog is available at: http://www.ewascatalog.org.
B3257 - Meta-analysis of association between MC3R Thr6Lys and Val81Ile polymorphisms and body mass index / obesity status - 12/03/2019
B3261 - Genetic and epigenetic approaches to identify factors influencing paternal participation in birth cohort studies - 19/02/2019
Paternal participation in cohort studies is lower than maternal
The mother is often considered the âgatekeeperâ to paternal involvement
This can introduce selection bias that can make maternal effects appear relatively stronger than paternal effects
For example, a previous study found that paternal participation was lower for mothers from low SEP, ethnic minorities, and those who smoke. This would contribute to any paternal effect of these factors on offspring health appearing smaller and weaker than any maternal effect.
A better understanding of the factors that influence paternal participation will enable researchers to develop strategies to increase paternal participation, thereby reducing these issues with bias. It will also highlight scenarios that might be subject to selection bias, which will help with interpretation of results.
Hypothesis-free approaches, such as those involving genetic and epigenetic âomic data, can help identify factors that influence paternal participation without reliance on/bias from the researchersâ assumptions.
This project aims to use genetic and epigenetic approaches to identify factors associated with paternal participation in birth cohort studies.
B3258 - STOP Science and Technology in childhood Obesity Policy - 20/02/2019
B3254 - Exploring causal links between psychological factors and continence problems - 07/03/2019
It is commonly believed that continence problems affect only young children and the elderly, but these problems can affect people of all ages. Despite their high prevalence and adverse effects, research into the causes, prevention and treatment of continence problems is scarce. Clinicians recognise that psychological factors are strongly associated with continence problems but research is needed to examine whether these factors actually cause continence problems.
The proposed research will use cutting edge statistical methods to examine whether there are causal effects of psychological factors on continence problems in childhood, adolescence and adulthood. The psychological factors we will examine include depression, anxiety, emotional and behaviour problems, stressful life events, maternal mental health, parenting, and childhood adversity. We will investigate whether characteristics relating to the child (e.g. toilet anxiety), parents and wider influences (e.g. peers, school) may help to explain the association between psychological factors and continence problems. We will also examine the role of inflammation as a biological process that might underlie the link between psychological factors and continence problems.
If we find evidence that psychological factors cause continence problems, this could help clinicians to develop more effective interventions and treatments. Ultimately, our research could improve the lives of people affected by continence problems and help the NHS make better use of its resources.
B3255 - Microalbuminuria causes and long-term consequences in the general population - 29/04/2019
Albumin is a protein present in blood and excreted in urine. Slight increases of levels of albumin excretion in urine (so called microalbuminuria) are related to an increased risk for renal and cardiovascular disease, even in otherwise healthy individuals. Nevertheless, the exact cause and the underlying mechanism of microalbuminuria are still unknown. Moreover, data on microalbuminuria in young individuals are scarce.
With this project we intend to learn more about the prevalence of microalbuminuria in school-aged children and young adults. We also want to test the hypothesis that some individuals have higher urinary albumin levels already early in life, that these findings persist in time and that such individuals carry a higher risk for renal, cardiovascular and, possibly, metabolic disease.
Moreover, we intend to explore possible causes of microalbuminuria, evaluating genetic background and associations between albuminuria and antenatal and postnatal determinants.
We plan to integrate the extensive data from the ALSPAC cohort with data from the Dutch GECKO birth-cohort (Groningen, The Netherlands), where urine samples have been collected at a younger age and thorough information about obesity risk factors are available. By investigating these two cohorts, we aim to gather data describing the spectrum of albuminuria from early childhood into young adulthood.
B3251 - The Relationship between Metabolic Dysfunction and Psychosis - 13/02/2019
B3256 - Using smartwatches to explore patterns of alcohol use - 14/02/2019
In this study we will explore the feasibility of using smartwatches to capture detailed information about individuals alcohol drinking behaviours. We will be using an approach called Ecological Momentary Assessment (EMA) to gather data about people's alcohol consumption as they go about their normal lives. Specifically, we will be using a new version of EMA called microEMA, which is designed to minimise the level of interuption and burden to people, whilst allowing us to capture detailed data about their drinking behaviours. We have developed a microEMA application to run on a normal, commercially available smartwatch, and will use this, alongside a more traditional questionnaire, to capture information about the type and quantity of alcoholic drinks consumed during each day, and if these drinks are consumed at home or outside the home, and in the company of others or alone. We will do this over a period of 3 months. Because we will ask people about their drinking behaviours throughout the day, we hope to capture more accurate and detailed information about their drinking behaviour with our smartwatch microEMA application than with traditional questionnaires, which people complete days afterwards, and which are known to suffer from problems related to remembering what was consumed, and other reporting biases. We can then use these data to explore differences in drinking behaviours between different groups. We will explore differences in drinking behaviour between high and low social economic position groups. This will allow us to understand, not just the differences in drinking behaviours between the two groups, but if there are differences in the way the two groups use and experience the new smartwatch-based microEMA approach, if this if different to the way they use and experience more traditional questionnaire approaches, and if new approaches like micro EMA might introduce other unexpected biases that could affect the data they collect.
B3252 - Genome Wide Association of Study of Adverse Childhood Experiences - 19/02/2019
Genome-wide association studies (GWAS) have been instrumental in highlighting associations between genetic variants and 1000s of traits. Adverse Childhood Events (ACEs) are associated with several adverse outcomes in life. We plan to include ALSPAC data from the mothers and the children in a GWAS of Adverse Childhood Events. This will be a big step towards incorporating ALSPAC data into psychiatric genetics. The summary statistics will contain no identifiable information.
B3250 - PACE maternal mid-pregnancy Vitamin D and offspring cord blood methylation - 07/02/2019
Low maternal vitamin D during pregnancy has been associated with a wide range of health outcomes in offspring, including bone health, symptoms of Attention Deficit-Hyperactivity Disorder, symptoms of Autism Spectrum Disorder, and autoimmune conditions. Methylation is one mechanism by which maternal vitamin D in the prenatal period might impact offspring health. We propose to test associations between maternal mid-pregnancy Vitamin D and offspring cord blood methylation. To maximise power, we will meta-analyze associations in multiple cohort studies including ALSPAC within the Pregnancy and Childhood Epigenetics consortium (https://www.niehs.nih.gov/research/atniehs/labs/epi/pi/genetics/pace/ind...).
B3248 - Alcohol use breastfeeding and offspring neurodevelopment - 05/02/2019
Breastfeeding is recommended as the best source of nutrition in early life by the WHO. However, mothers who consume large quantities of alcohol while breastfeeding might be harming their offspring because of this âpassiveâ alcohol exposure in the postnatal period. Realistically, in the UK and other developed countries, only a minority of mothers will be consuming alcohol to excess while breastfeeding and caring for a young baby, while most mothers would consume alcohol occasionally and in moderate quantities. These levels of consumption have not been linked with definite harms or benefits to the child so far, with only a few studies examining this question and achieving conflicting results. We propose to investigate the association between early post-natal alcohol exposure and measures of offspring physical and neurological development, including risk of Foetal Alcohol Spectrum Disorder (FASD), in a large UK-based sample representative of the population and followed-up since antenatal appointments, the Avon Longitudinal Study of Parents And Children (ALSPAC).
B3249 - Utilising ALSPAC as a population control set for Head and Neck 5000 - 12/03/2019
Genetic studies often need to compare diseased participants with healthy participants. In this project, a study of Head and Neck Cancer patients (HN5000) has no healthy participants to compare to. Therefore, participants in ALSPAC are going to be utilised as healthy genetic controls. To do this successfully some ALSPAC participants, who've already had their genetic data measured, will have it remeasured alongside the HN5000 participants. By doing this any errors that may occur in the laboratory process can be identified rather than potentially contributing to false findings. Once this cross-check is complete all ALSPAC participants (unless already diagnosed with HNC) can be used as healthy controls which will greatly increase the utility of the HN5000 study.
B3245 - Econometrics of loneliness - 30/01/2019
Loneliness has, in recent years, become a priority in national public health agendas in developed countries, given increasing recognition of the detrimental effects of loneliness on health and mortality. The literature has often focussed on loneliness among older adults, but recent surveys have revealed a similar prevalence among younger adults up to age 25.
The aim of this research project is to understand whether circumstances and experiences from childhood can be linked to loneliness and social isolation reported in adulthood. The ALSPAC also contains multiple reports of loneliness across teenage years and young adulthood, which would allow us to understand its dynamics; for example, whether there are different patterns of loneliness across time between individuals. Rich reports of physical and mental health, including disease-related biomarkers, would also aid in analysing relationships between loneliness and health, to complement evidence seen in later adulthood.
It is imperative to identify individuals at higher risk of loneliness in later life, and early life events or circumstances that can play an important role in predicting later life loneliness, towards reducing societal loneliness via public policy and private decisions. Identifying factors from early life, rather than contemporaneous factors, is beneficial to inform early preventive strategies, and to target such factors rather than mechanisms (via which these factors operate) for more efficient allocation of resources. Understanding whether and how loneliness is predictive of poor health earlier in life may also provide some insights into the mechanisms via which loneliness predicts excess mortality in late adulthood.
B3246 - MAPS mapping the analytic paths of a crowdsourced data analysis - 04/02/2019
In order for the public to have faith in the conclusions of scientists it is important that the methods they employ are robust and transparent. This is especially important for controversial topics with major implications for mental health. The public should rightly demand that such findings are not contingent on the beliefs of the scientists, their particular methods, computational quirks or simple accident. This is of particular relevance when total transparency is not possible because the data is sensitive.
This study addresses the question of robustness by taking a controversial question, âIs there an association between screen time and depression and anxiety?â, recruiting teams of independent data analysts and looking at how they answer the question using the same data, effectively âcrowd-sourcingâ the data analysis.
The study will use the answers teams provide to this controversial question to answer further questions such as: âDo the methods used to answer the question influence the result and if so by how much?â and, âDo the beliefs and particular expertise of the analysts influence their results?â. To do this, we will use a statistical technique called a âmultiverse analysisâ, whereby reasonable alternatives to choices made by the teams, during the data analysis, are explored and recorded to see how sensitive the results were to the choices made.
To ensure the study is transparent we will investigate the use of anonymised data. Using anonymised data is controversial as the anonymisation process may erase important features of the data. This study will ask âDoes the anonymisation process affect the results and if so by how much?â.
The answer to all these questions will help us understand how scientists arrive at answers to controversial questions and whether crowd sourced analysis and data anonymisation techniques can ensure findings are robust and transparent.
Finally, our study will challenge the teams to come up with interesting ways to visualise the answers to these questions in exchange for a prize. Visualising the teamsâ answers, along with how robust they are, in a clear, accessible way will be important to help communicate complex results both for this study and in the future.