Proposal summaries
B3090 - Epigenetics in peer victimization and behavioural and emotional development - 05/04/2018
Peer victimization is a widespread phenomenon with many harmful and persistent consequences, such as anxiety, depression, and even suicidal ideation. However, consequences of can vary widely in presentation and severity, which hinders development of appropriate interventions targeted at alleviating the effects of peer victimization. This may in part stem from the fact that little is known about the biological mechanism through which bullying affects children's psychological development and wellbeing. Therefore, we aim to study how peer victimization is related to epigenetic development and explore to what extent epigenetics mediate the association between peer victimization and negative outcomes in children. We will do this by combining data of two large comparable cohorts, ALSPAC in England and Generation R in Holland.
B3095 - Genome-wide association analysis of voting behaviour for Mendelian randomization - 11/04/2018
Genome-wide association studies (GWAS) have been critical in identifying thousands of genetic variants associated with complex traits and diseases. For certain complex traits however, it may be the case that there is difficulty in phenotypic measurement and this can lead to issues of statistical power. This is particularly problematic for behavioural phenotypes that may be predominantly determined by the environment, as is the case for educational attainment and well-being (Okbay et al., 2016; Okbay et al., 2016; Rietveld et al., 2013). Genetic analyses of such phenotypes can be hindered by the fact that individual SNPs have limited explanatory power and any associations found may not be causal or may be mediated by many other intermediate phenotypes (Krapohl et al., 2014). However, such studies have enabled the description of common genetic contributions to complex behaviours. Taken together, these GWAS results form a pool of genetic variants which may then be used in Mendelian randomization (MR) analyses; both looking at the effect of these features on outcomes but also the effect of outcomes on them.
This project will use newly collected data in the Avon Longitudinal Study of Parents and Children cohort to analyse voting behaviour. Firstly, we aim to conduct a GWAS on voting behaviour to discover any genetic variants associated with this complex trait. Additionally, we plan on considering the potential of using MR analysis to look at this behavioural phenotype. Specifically, we aim look at the effect of well instrumented risk factors on voting behaviour itself, i.e. âbackwards MRâ.
References
Krapohl, E. et al. The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence. Proc. Natl Acad. Sci. USA 111, 15273â15278 (2014).
Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses (vol 48, pg 624, 2016). Nature Genetics 48, 1591-1591 (2016).
Okbay, A. et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533, 539-+ (2016).
Rietveld, C.A. et al. GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment. Science 340, 1467-1471 (2013).
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.
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.
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.
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.
B3106 - Does the effect of eating patterns at night on childhood weight status differ between the UK and China - 08/05/2018
It has been suggested that night eating is related to increased fat storage and therefore increased body weight. There is also no clear definition of what is meant by night eating. The potential effects of night eating on obesity have primarily been examined in adults to date and any studies in childhood have been cross-sectional, with none in the UK. Based on information collected in diet diaries at the age of 7, this project will aim to examine different definitions of night eating and examine the effects on childhood weight status and it's change over time. This will be carried in two different cohort studies - one based in the UK and one based in China.
B3108 - Longitudinal patterns and predictors of multiple cancer-risk behaviours among UK adolescents - 08/05/2018
Using two British cohort studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Millennium Cohort Study (MCS), this fellowship will explore the longitudinal patterns and predictors of multiple cancer-risk behaviours (MCRB). MCRB are modifiable behaviours including tobacco smoking, alcohol consumption, physical inactivity, overweight and obesity, unhealthy diet and risky sexual behaviour that are associated with cancer incidence and mortality. Rather than focusing on specific cancers this research will cover a wide range of cancers that are associated with these behaviours.
B3111 - Time-dependent associations between body mass/body composition physical activity diet and lung function in childhood - 08/05/2018
The large increase in the prevalence of respiratory diseases over the last decades, in the West more particularly, cannot be explained by genetics only. It has been hypothesized that these increases are a consequence of changing environmental and/or lifestyle factors. Given the multifactorial aspect of these diseases, it is thus important to take into account the interrelations between these factors and respiratory health. The interrelations between body mass/body composition, physical activity, diet and lung function in childhood and adulthood have been incompletely addressed, likely because their time-dependent and bidirectional nature represent a methodologically challenging research question. Marginal structural models (MSMs) allow estimation of causal effects in observational studies by addressing time-dependent confounding (Robins JM et al. Epidemiology 2000). This approach has still limited application in respiratory epidemiology. We aim to investigate the joint and independent causal effects of body mass/body composition, physical activity and diet on lung function during childhood and early adulthood using MSMs in children from the ALSPAC study.
B3113 - NIHR Bristol BRC - Exploring Mental Health and Cognition using Mendelian randomisation - 24/05/2018
Treatment for mental illness often focuses on changing cognitive patterns (for example, cognitive behavioural therapy). There is much evidence to suggest that cognition is different in those with mental illness but whether change in cognition is a causal risk factor has not yet been established. Classic observational studies of cognitive patterns and mental illness do not get around the problems of reverse causation and residual confounding. That is to say that the change in cognition might instead emerge as a result of the mental illness, or both might be the result of other unmeasured factors.
One way to get around this is using Mendelian randomisation. Here we take genetic variants associated with the trait of interest: cognition and use them to naturally randomise individuals to levels of the exposure. Therefore, analogous to a randomised control trial, we can make conclusions about whether or not the relationship is causal. In this study, we will be looking at the cognitive traits of emotion recognition, working memory, cognitive styles and impulsivity. This research could inform the development of cognitive training tasks as interventions for mental illness.
B3080 - Micronutrients in Mood Disorders - 24/05/2018
Depression and anxiety disorders are becoming increasingly common. There is some research suggesting that our diet, (what we eat) might make us more likely to become depressed and anxious. This type of research is called 'Nutritional Psychiatry' research. Many research studies have shown that people with depression and anxiety disorders do not have enough of certain 'micronutrients' either in their food, or in their blood. One example is magnesium, which is contained within green leafy vegetables, and is lacking in processed foods. It is possible that our society is not consuming enough magnesium, which could be increasing the number of people with depression and anxiety. However, it is difficult to say whether a low magnesium in depressed people was the cause of their depression. It may be because people with depression eat less healthily, or because people with other problems (alcohol use or long term illnesses) are more likely to get depressed.
This research will aim to get around these difficulties by using our DNA or genetic code to look at whether genetic changes that cause us to have lower magnesium, are also linked to us having depression.
B3118 - Genome-wide association study of anxiety and depression - 24/05/2018
Genome-wide association studies (GWAS) have been instrumental in highlighting associations between genetic variants and 1000s of traits. A recent GWAS of major depressive disorder (MDD) by the psychiatric genetics consortium (PGC) has recently identified 44 genetic variants associated with the disorder (Wray et al., 2018). We plan to include ALSPAC data from the mothers and the children in the next round of analysis for both forthcoming MDD and anxiety PGC GWAS. We will prepare summary statistics from the GWAS to be shared with the PGC and perform subsequent in cohort analysis. This will be a big step towards incorporating ALSPAC data into psychiatric genetics. The summary statistics will contain no identifiable information.
B3114 - Tracking Sleep Phenotypes 2 15-05-2018 - 234902 - 26/05/2018
Sleep matters to those who care for young children. The duration and timing of sleep can have a profound effect on a young childâs everyday behaviour, learning and health and also has a significant impact on the routines and wellbeing of the adults who provide his or her care. Yet there is surprisingly little evidence regarding the developmental function of early sleep patterns. Current understanding of the processes underpinning normative transition in sleep patterns, the prevalence of specific sleep phenotypes and persistence in sleep patterns across time is limited. This study will utilise genetic and environmental data, alongside longitudinal sleep data to examine the prevalence, persistence and developmental significance of childhood sleep phenotypes.
This knowledge will inform clinical, public health and educational policy and practice where management of sleep is an issue of controversy and also inform parenting practice where early child sleep behaviours can have a major impact on family functioning, parent well-being and child development.
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.
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.
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).
B3124 - Using the power of DPUK cohorts to explore childhood adversity and adult behavioural psychological physical cognitive and b - 06/06/2018
Childhood adversity could cover many things including extreme difficulties and adverse experiences during childhood such as sexual, physical and emotional abuse, deprivation, and family dysfunction. Experiencing adversity during childhood may have a dramatic effect on a child's life. It has been linked to a number of poor outcomes in adulthood such as worse health outcomes, poor mental health, reduced life satisfaction and dementia. One in three adults diagnosed with mental health conditions are reported to have experienced childhood adversities therefore, there is the potential for life-long associations between childhood adversity and health, which need to be evaluated and accounted for. The proposed project will examine childhood adversity in three different UK populations and in a birth cohort and associations with a number of different outcomes including physica and mental health, poor lifestyle choice such as unhealthy diet, smoking and binge drinking and antisocial behaviours.
B3125 - Trajectories of Weight and Obesity From Birth to Adulthood According to Polygenic Susceptibility - 06/06/2018
We want to quantify what the impact of genetics across the whole genome has on weight and risk of severe obesity from birth to middle adulthood.
B3127 - Maternal caffeine intake during pregnancy An epigenome-wide association study - 06/06/2018
Rationale: Animal studies have provided some evidence that maternal caffeine consumption can influence offspring DNA methylation (PMIDs: 22970234, 24475304, 25354728, 25868845, 25868845), but what about humans?
B3129 - Longitudinal intake of free sugars in ALSPAC children 06-06-2018 - 151010 - 06/06/2018
The current recommendation is that we should limit our intake of free sugars to provide less than 10% of daily energy intake. This study will investigate free sugars intake in ALSPAC children at ages 18 months, 3.5, 5, 7, 10 & 13 years and determine whether those consuming less than 10% energy from free sugars have a more beneficial nutrient and food group intake than those that consuming more free sugars. Then to investigate if there are differences in obesity levels in relation to free sugars intakes.