Proposal summaries
B3096 - Does cognitive vulnerability modify the association between stressful life events and future depression - 11/04/2018
Several studies have found that the experience of stressful life events (ranging from more severe events, such as divorce or bereavement, to daily hassles, such as family-related obligations) can lead to symptoms of depression. However, the impact of these events varies, and not everyone who experiences a stressful event goes on to experience depression. Weâre interested in studying whether cognitive vulnerability, the tendency to make negative causal inferences about an event, can explain this difference (i.e., is an effect modifier). That is, the interpretation of the event, rather than exposure to the event alone, may be particularly important for predicting future depression. This study aims to investigate how the impact of stressful events varies between people, and why certain people go on to experience depression while others do not. These findings could inform potential targets for interventions which intend to prevent depressive symptoms.
B601 - Maternal reproductive history and the outcome of labour
B3072 - BIOMAP - Genome-Environment Interactions in Inflammatory Skin Disease - 06/03/2018
Atopic dermatitis (AD) and psoriasis affect a substantial percentage of the population. The mechanisms of disease, endotypes, co-morbidities of these diseases remain poorly understood. There is need to define the heterogeneous and homogeneous aspects of AD and psoriasis and identify the impact of environmental factors, genetic factors and molecular pathways. This will give rise to more precise targeted treatments. The BIOMAP project will bring together existing resources from European cohorts and industry to meet this challenge. ALSPAC, with it's rich longitudinal phenotyping and molecular data is well suited to contribute to this project.
B3097 - A meta-analysis of maternal smoking GFI1-CpGs and cardio-metabolic phenotypes in adults - 17/04/2018
Individuals exposed prenatally to cigarette smoke tend to have lower birthweight and have higher risks for a variety of detrimental health outcomes later in life. Cigarette smoke exposure is also associated with DNA methylation changes at gene GFI1, and recent evidence suggests that these changes may play a role in the lower birthweight of exposed infants. We would like to determine if there is evidence that these DNA methylation changes may also play a role in risk factors for other health outcomes of prenatal cigarette smoke exposure. We would specifically like to investigate factors related to cardiovascular and metabolic health.
B600 - Investigation of the role of bone size relative to body size in the pathogenesis of fractures in childhood
Aims
(i) Whether changes in bone size relative to body size contribute to the increased risk of fracture during puberty will be established, by examining the relationship between longitudinal changes in these parameters across puberty.
(ii) Whether the higher risk of fracture in pubertal boys compared to girls is related to gender differences in bone size relative to body size will be determined.
(iii) Whether small bone size relative to body size represents a stable trait that once established in childhood persists following puberty will be investigated.
B2714 - Latent disease risk for coronary artery disease sample based recall by genotype for detailed metabolomic screening - 03/05/2017
This project looks to understand how genetic predisposition to coronary heart disease is manifest in early life. The idea here is that although young people have not yet presented with adult/mature disease, there may be metabolic signatures of later life disease risk which differ by genetic factors and are which mark carriers of these genotypes as different. Importantly, showing differences in metabolic profile at earlier ages may lead to the ability to target and modify these factors to aid later life disease risk.
B3073 - Development of Caetanos discontinuity endogeneity test and application to the effect of vegetarianism on health - 06/03/2018
Observing that an exposure (e.g. higher meat intake) is associated with an outcome (e.g. higher BMI) does not necessarily mean that the exposure caused the outcome. Other factors may "confound" the association by causing both the exposure and the outcome. Such confounding can be difficult to detect if the factors responsible have not been measured. A recent study proposed a method to detect confounding by unmeasured variables if they cause discontinuous variation in the exposure. We intend to develop this method further and apply it to the question of whether eating meat affects a person's BMI. The method should tell us whether simple observation of people's meat intake and BMI reveals the causal effect or is confounded.
B3109 - Predictive genomic classifiers for the risk assessment of common learning disabilities in children - 29/05/2018
Learning disabilities are common disorders characterized by unexpected difficulty with a specific mode of learning in the context of adequate intelligence and academic opportunity. The high prevalence of these disorders in the general population represents a costly burden to the educational system and affected individual are often at risk for long-term adverse psychological and socioeconomic outcomes. Intervention programs work, but are more effective when tailored to individuals and administered earlier in life. The pre-symptomatic detection of individual who are at risk of developing learning disabilities, and who are more likely to benefit from early intervention, is therefore an important diagnostic opportunity with major economic and societal implications. The objective of this project is to evaluate the diagnostic performance and predictive value of genetic variants associated with learning disabilities in the ALSPAC cohort.
B3091 - Solids and formula feeding as risk factors for morbidity in infancy - 29/03/2018
A recent large scale evidence review has demonstrated the importance of exclusive breastfeeding to 6 months with partial breastfeeding continued though the first year of life, but few studies have considered whether starting solids earlier than 5-6 months, but with continued breastfeeding, increases the risk to health or causes earlier cessation of breastfeeding.
The review also found new evidence from the developing world that giving extra iron in children who are not short of iron may cause increased infections and slower growth. Formula milks which have higher iron content than either breast milk or doorstep milk are currently recommended from 6 months to 12 months where an infant is not breastfeeding to prevent iron deficiency anaemia and iron fortified follow on formulas are widely advertised. However the potential risks of iron supplemented formula milks have never been examined.
B3099 - Lung function growth and residential greenness in the ALSPAC cohort - 19/04/2018
There is increasing evidence that residential greenspaces (proximity to and amount of green spaces and vegetation around a person's home) may be associated with various health outcomes, including increased physical activity levels and respiratory health outcomes, such as asthma. As lung function is associated with both physical activity and asthma, it could thus also be associated with greenspaces. However, to date, no study has examined whether an association between residential greenspaces and lung function exists in children, and what potential pathways may be playing an important role. Using the ALSPAC data, this study aims to fill this research gap.
B3110 - Computational Models for the Prediction and Prevention of Child Traumatic Stress - 29/05/2018
More than 20% of children will experience a traumatic event before they are 16 years old. Of those who experienced a trauma, a sizable minority will develop Posttraumatic Stress Disorder (PTSD), and other deleterious developmental, health, and psychiatric consequences (herein called Child Traumatic Stress). To diminish the considerable burden of traumatic stress on children and their families, the capacity to predict a childâs risk and to intervene to diminish this risk is extremely important. The literature on prediction of child traumatic stress from risk factors has yielded only modest results and - of those risk factors found to be predictive â it is difficult to determine which represent processes would lead to a diminution of risk, if effective intervention were applied. Almost certainly, traumatic stress results from a complex set of interacting bio-behavioral and social environmental processes, unfolding in specific ways over the course of development, and related to specific aspects of the traumatic exposure. Our project aims to apply state-of-the-art Machine Learning predictive modeling methods with a wide array of risk variables from the ALSPAC data set to generate reliable and accurate predictive models of PTSD and other child traumatic stress outcomes. We also aim to apply advanced non-experimental causal discovery algorithms to discover potentially remediable processes leading to traumatic stress outcomes that may reveal new opportunities for preventative intervention.
B3075 - Genetic vulnerability to schizophrenia and major depressive disorder and the risk of childhood adversities - 08/03/2018
Since the recent publication of large genetic studies to identify genetic risk factors for debilitating psychiatric disorders such as schizophrenia and depression, it has been possible to use this genetic information to study to what extent genetic risk to, for example, schizophrenia or depression predict risk for psychiatric problems prior to the development of clinical disorders. Particularly interesting is to investigate how a child's genetics make him or her more vulnerable to the exposure of stressful life events. Moreover, it is still unclear to what extent this relationship mediates the association between genetic risk and childhood psychiatric problems.
B3093 - Traits phenotypes and prognosis of childhood asthma - 29/03/2018
The proposal is to continue the collaborative work we have been doing with this Swiss group over the past few years. Ben Spycher was a Marie Curie Fellow who worked with ALSPAC data previously. Prof Kuehni leads eth Leicester Asthma Cohorts and has established the Swiss Paediatric Airway Cohort (SPAC). OUr joint objective is to discover influences that determine the onset and progression of asthma in children, how asthma varies between individuals in type and severity and whether we can predict the outcome of asthma using individuals' information. The data in eth Leicester adn Swiss cohorts is complementary to data held in ALSPAC and we have had joint publications where ALSPAC is able to replicate findings in the other cohorts run by the Swiss group.
B3104 - Impact of Breastfeeding on Cardiovascular and Metabolic Outcomes in Women with a History of Hypertensive Disorders of Pregnancy - 26/04/2018
Women who experience a hypertensive disorder of pregnancy are at greater risk for diseases of the heart and blood vessels. Breastfeeding may reduce this risk in women in general and particularly in those who have had a hypertensive disorder of pregnancy. This proposed study will examine if the duration/amount of breastfeeding has a beneficial effect on markers of heart health in later life in women who did and did not develop a hypertensive disorder of pregnancy.
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B3078 - Single SNP Replication of rs71564871 - 08/03/2018
A single mutation within the genome (called rs71564871 near a gene called BEND6) has been previously linked to fat distribution in the body, specifically the proportion of fat stored across the waist compared to the hips, in women of the ORCADES study and UK Biobank. Within this study, we want to assess whether this single mutation is similarly related to the same pattern of fat deposition in the Avon Longitudinal Study of Parents and Children.
B3088 - Metabolic profile of prediabetes using genetic susceptibility and repeat metabolomics to inform early detection - 29/03/2018
Type 2 diabetes develops for many years before it is diagnosed. Using data from ALSPAC offspring, we aim in this study to harness genetic susceptibility to adult type 2 diabetes and detailed metabolic profiling to better understand the early stages of diabetes development that are detectable in blood. This will involve describing associations of a genetic risk score comprised of hundreds of genetic variants for adult type 2 diabetes with hundreds of metabolic traits from targeted metabolomics at four key stages of early life â childhood (age 8y), adolescence (age 15y), early adulthood (age 18y), and formal adulthood (age 25y) â to view subtle changes in metabolism over time which precede the onset of clinical diabetes. Recognizing the early signs of diabetes is vital for early detection and for preventing downstream cardiovascular diseases and cancers.
B3122 - Genome-wide analysis of selection and methylation - 06/06/2018
Human evolution has been associated with drastic changes in environment and lifestyle over time, with each of these changes resulting in selective pressures (Voight et al., 2006). Natural selection is the differential reproductive success of genetically distinct individuals or genotypes within a population. Strongly deleterious mutations will rapidly be eliminated from populations, whereas strongly positive mutations will quickly rise to fixation leading to changes in allele frequency over time. This process leaves signatures on the genome which can then be detected (Sabeti et al., 2006).
Epigenetics refers to heritable changes outside of the DNA sequence itself and provides a potential mechanism by which environmental and lifestyle exposures can impact gene expression over the course of a lifetime. Epigenetic mechanisms can include DNA methylation and histone modifications. DNA methylation is the most widely studied epigenetic change and involves the addition of methyl groups to nucleotide bases (Vocht et al., 2018).
Natural selection is a long term, multigenerational response to environmental factors that can influence the role of genes in human traits (Bamshed and Wooding, 2003) whereas epigenetic inheritance allows stable changes in DNA methylation to be passed from one generation to the next (Feil and Fraga, 2012). Both selection and methylation act in response to environmental exposures but over different timescales. This project will aim to unravel the interplay between selection and methylation to assess whether DNA methylation offers a mechanism to respond to exposures in the short term which may eventually lead to changes in allele frequency.
References
1. Bamshad, M. & Wooding, S.P. Signatures of natural selection in the human genome. Nature Reviews Genetics 4, 99-111A (2003).
2. de Vocht, F. et al. DNA methylation from birth to late adolescence and development of multiple-risk behaviours. Journal of Affective Disorders227, 588-594 (2018).
3. Feil, R. & Fraga, M.F. Epigenetics and the environment: emerging patterns and implications. Nature Reviews Genetics 13, 97-109 (2012).
4. Sabeti, P.C. et al. Positive natural selection in the human lineage. Science 312, 1614-1620 (2006).
5. Stearns, S.C., Byars, S.G., Govindaraju, D.R. & Ewbank, D. Measuring selection in contemporary human populations (vol 11, pg 611, 2010). Nature Reviews Genetics 12, 1 (2011).
6. Voight, B.F., Kudaravalli, S., Wen, X.Q. & Pritchard, J.K. A map of recent positive selection in the human genome (vol 4, pg 154, 2006). Plos Biology 4, 659-659 (2006).
B3554 - Asthma and COVID-19 - 08/06/2020
Asthma affects the lives of 5.4 million people across the UK. COVID-19 attacks the lungs and can trigger asthma symptoms like wheezing, chest tightness and difficulty breathing, which is very distressing for patients and can cause feelings of anxiety. We want to know if participants with asthma at 23-24 years were more likely to report respiratory symptoms, mental health issues, shielding during the COVID-19 lock-down.
We'll also be interested to explore differences between people with asthma and COVID-19 related symptoms and people with asthma and non-related COVID-19 symptoms, e.g. economical status, asthma severity....
B3087 - INTIMATE PARTNER VIOLENCE PERPETRATORS THE ORIGINS - 29/03/2018
Intimate Partner Violence (IPV) is defined as any violent behavior within an intimate relationship or any other controlling behavior that is conducted by a current or former partner. It is the most common form of violence in women which constitutes a major public health problem worldwide. The current explanatory theories of IPV perpetration can be summarized as feminist/sociocultural, social learning theory-based intergenerational transmission and psychological/psychosocial. According to the feminist/sociocultural theory, domestic violence is a consequence of âpatriarchyâ. From this view, violence is used as a form of power and control of women by men. The intergenerational transmission theory asserts that domestic violence is based on the exposure to, or observation of, violence in the family of origin. Psychological theories propose that there are psychological, psychiatric, behavioural and neurological risk factors for domestic violence perpetration. In the study of IPV perpetration, it is important to consider the variables addressed by such theories as a whole and from a developmental perspective and there is no study that simultaneously considers all the variables of these explanatory theories. The general aim of our study is to identify those etiological mechanisms linking risk factors for IPV perpetration across development. This study will be the first one that sheds light on which the origins of IPV perpetration are by knowing how IPV perpetration develops. Implications in terms of prevention and treatment will be of a great relevance for public health.