Proposal summaries
B4222 - Early-life vitamin D status and lung function in childhood and adolescence observational and mendelian randomization analyses - 19/12/2022
In this study we aim to analyse whether or not vitamin D levels during pregnancy influence lung development and, consequently, the occurrence of asthma and lung function performance in childhood and adolescence. To analyse these associations, we will use two methodologies. First, we will look at whether or not vitamin D levels measured in blood during pregnancy are associated with the onset of asthma and lung function parameters at 8-9 years and 15-16 years in the ALSPAC cohort. Since this association may be influenced by many confounding factors such as lifestyle, socio-economic status, the season of the year when the blood was obtained, we will use Mendelian Randomisation to overcome this limitation. We will analyse whether or not genetic variants that predispose to having low levels of vitamin D are associated with a greater predisposition to having asthma and poorer lung function in childhood and adolescence. We will use data from 4 different European cohorts and one Australian cohort and, after doing all the analysis separately, we will collect the results and do a meta-analysis using all data.
B4225 - Polygenic risk score of asthma COPD and lung function and association with lung function outcomes - 19/12/2022
Genetic variants associated with lung function and susceptibility to airway diseases such as asthma or COPD might be implicated in lung function development from birth to adulthood. Here, we would be able to assess whether very low and low lung function trajectories are primarily associated with asthma, COPD, or lung function genetics, and related mechanisms. Disentangling the genetic factors derived from asthma, COPD, and lung function studies underlying the trajectory of poor pulmonary capacity across the lifespan could contribute to identifying new lung function biomarkers and to early prevent the development of chronic airway diseases. By using a PRS approach, we anticipate having better power to evaluate asthma and COPD mechanisms in lung function trajectories compared to a standard GWAS approach.
B4226 - Religiosity Confounders Mediators and Bidirectional Causality - 19/12/2022
Key to causal inference from observational data is adequate adjustment for confounders (i.e., factors which cause both the exposure and outcome). However, knowing whether a variable is a confounder (requiring statistical adjustment) or a mediator (i.e., a variable caused by the exposure which in turn causes the outcome; not requiring statistical adjustment) is often difficult to establish with certainty and often relies upon potentially-debatable assumptions. By making use of the repeated data collected by ALSPAC - both in terms of religiosity and data on other covariates which may be plausible confounders and/or mediators - it is possible to make reasonable inferences as to whether religiosity causes the covariate, the covariate causes religiosity, or indeed whether there is bidirectional causation (i.e., religiosity causes the covariate and the covariate also causes religiosity). If data permit adjustment for baseline confounders, prior exposure and prior outcomes, then it may be possible to infer causality using longitudinal observational data (VanderWeele 2021; VanderWeele et al., 2016). We intend to apply these methods in ALSPAC to explore potential bidirectional causation between religiosity and a range of covariates to better understand these patterns and to help inform future work using these data.
References:
VanderWeele, T. J. (2021). Can sophisticated study designs with regression analyses of observational data provide causal inferences?. JAMA psychiatry, 78(3), 244-246.
VanderWeele, T. J., Jackson, J. W., & Li, S. (2016). Causal inference and longitudinal data: a case study of religion and mental health. Social psychiatry and psychiatric epidemiology, 51(11), 1457-1466.
B4184 - Gender-based violence over the life course using cohort data from the Avon Longitudinal Study of Parents and Children - 19/12/2022
Gender-based violence (GBV) is a global public health problem. It is present in all ages and socioeconomic statuses. However, a better understanding of GBV over the life course and the long-term impact of violence exposure on health outcomes is still required. Therefore, the objective of this project is to evaluate and understand gender-based violence over the life course and the many factors involved in this violation of women's and children's human rights. To do this, we will use the ALSPAC cohort study, which include among others a range of both parent and self-reported questions related to gender-based violence, such as data on physical, psychological, and sexual violence occurring during different periods of life. Using this data, it will be possible to estimate (i) cumulative exposure to GBV; (ii) the intergenerational exposure to GBV; (ii) the differences in GBV considering gender, age, education, and income level; and (iv) the impact of violence exposure on health outcomes.
B4212 - Improving treatment of menopausal symptoms by using genomics to understand aetiology - 22/12/2022
Menopausal symptoms affect around 70% of women as they go through the menopause, but we don't know very much about what causes the various symptoms. It is not clear how different symptoms might be linked and who is at risk of developing them. We will use genomics to find the causes of a range of menopausal symptoms, including; hot flushes, sleep disturbance, mood changes and sexual dysfunction. We will develop a questionnaire to distribute to study participants to collect information about their symptoms and combine this with genomic data previously collected.
B4211 - Genetic architecture of feeling loved in childhood GWAS and genetic correlations - 14/12/2022
Research has shown that adults who look back on their childhood and say that they had a positive relationship with their parents, or felt loved by their parents, have better mental health. Indeed, these emotional memories can be more important for mental health than memories of specific behaviours that parents engaged in. However, we don’t know how the relationship between feeling loved in childhood and mental health actually comes about.
In this study, we will firstly look at how genetics relates to people saying they felt loved in childhood. People who took part in a large research study answered a question about whether they felt loved in childhood and provided a blood sample, so that we can look at their genetics. Genetic material (DNA) is made up of millions of tiny units called base pairs. At each base pair, a person can have one of two alleles. We will look at whether the allele that a person has at each base pair increases or decreases their likelihood of reporting that they felt loved in childhood. We will then look at whether there are similarities in how genetics contributes to feeling loved in childhood and depression, anxiety, and wellbeing.
This will help us to understand some of the reasons people are more or less likely to say they felt loved in childhood. It can also provide a better understanding of how feeling loved in childhood relates to mental health. All of this is important for how we understand the causes of mental health problems.
B4213 - Does religious practice moderate the association between adverse childhood experiences and weight trajectories in adult women - 09/01/2023
We aim to explore the associations between adverse childhood events (ACEs) and weight trajectory (diet change, alcohol consumption, and change in physical activity) amongst the G0 Mothers in ALSPAC. Also investigating whether religious beliefs and behaviours (and changes thereof) moderate this relationship and whether depression score mediates this relationship. In these analyses we will adjust for relevant confounders such as demographic characteristics, smoking status, and age.
B4214 - The joint effect of blood lead and vitamin D on preterm birth in the Avon Longitudinal Study of Parents and Children - 20/12/2022
Preterm birth, the leading cause of death in children younger than five, is a risk factor for brain-based disorders, asthma, and ischemic heart disease. Lead is a toxic chemical and a known risk factor for preterm birth. Vitamin D may modify this relationship due to its probable antioxidant properties.
In a recent pan-Canadian study examining 1,851 live births from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort, prenatal exposure to low concentrations of lead increased the risk of preterm birth and spontaneous preterm birth, and the risks were stronger among mothers with insufficient vitamin D levels, suggesting that they might be more susceptible to the toxic effects of lead. However, average blood lead concentrations among mothers were low among a modest sample size, and replication of these findings is warranted.
We aim to estimate the joint association of blood lead and vitamin D with preterm birth the Avon Longitudinal Cohort of Parents and Children.
B4221 - Identifying clusters of COVID-19 and Long Covid symptoms - 13/12/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4220 - UKLLC Mental health and COVID-19 vaccine outcomes - 13/12/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4210 - Cross-ancestry Epigenome Wide Association study EWAS of objectively measured physical activity in pregnancy - 14/12/2022
Physical activity (PA) during pregnancy reduces the risk of gestational diabetes mellitus (GDM) and excessive weight gain. DNA methylation (DNAm) - changes to DNA sequence but not the structure - is a potential molecular mechanism through which physical activity (PA) mediates the effects on the transcriptome. Original discovery analyses were run in a cohort from Norway (EPIPREG) and we want to replicate their findings to see if these CpG sites are associated with PA.
B4209 - PhD project on Placentas adverse pregnancy outcomes and cardiometabolic health - 20/12/2022
The placenta is a crucial organ of mammalian pregnancy, connecting mother and fetus. Impaired placentation and placental development and function are associated with common pregnancy complications including preeclmapsia, fetal growth restriction and preterm delivery.
Here we will investigate associations between placental weight, dimensions and number of cotyledons and pregnancy outcomes as well as the long term health of both mothers and their offspring. We will also use the genetic data in order to identify determinants of the placental traits.
B4207 - School lunch choices at age 13 years in persistent picky eaters in a longitudinal birth cohort study - 23/11/2022
The aim of the project is to look at foods and food group choices in school meals and snacks by children aged 13 years who were persistent picky eaters in the early years. The data were collected via questionnaires that the children completed themselves. Children with persistent picky eating habits during their early years have already been identified. Their choices will be compared with those of children who were not picky eaters.
B4206 - Intergenerational Cohort Consortium ICC - 28/11/2022
The primary objective of the Intergenerational Cohort Consortium (ICC) is to maximise the value of some of the most mature multi-generational data to complete a series of analyses (and associated publications) providing new insights into intergenerational pathways that connect parental life histories, from infancy to parenthood, to offspring psychosocial development decades later. Key outcomes include parent psychosocial adjustment and caregiving behaviour, and offspring psychosocial development. The aim is to identify modifiable factors that act to break intergenerational cycles of disadvantage and strengthen families from one generation to the next.
Planned analyses will specifically address questions about intergenerational transmission that cannot be answered in any one cohort. These include questions about the reproducibility and generalisability of findings reported from single studies; questions about intergenerational effects of low prevalence exposures (e.g., histories of illicit drug use and self-harm), and; questions which require contributions from different cohorts to provide a more complete picture of development processes (e.g., piecing together positive pathways from childhood to young adulthood).
Further information can be found in our ICC profile paper:
https://doi.org/10.1332/175795920X15792720930280
The ICC is a consortium within our broader LifeCourse initiative:
https://lifecourse.melbournechildrens.com/
https://doi.org/10.1093/ije/dyac086
B4205 - The intergenerational links between PRS of ADHD in mothers and childhood maltreatment in their children - 06/12/2022
Childhood maltreatment has a profound impact on both the short- and long-term wellbeing of children. Specifically, children with autism and those with attention deficit/hyperactivity disorder have a higher risk to experience maltreatment than those with typical development. However, the reasons why this is happening, are unclear. Two studies will be conducted. The first study will investigate the relationship between childhood maltreatment and ADHD. Studies support an association between ADHD and maltreatment: Children with ADHD have higher risk of experience maltreatment than those without ADHD, as well as people who suffered childhood maltreatment have high levels of ADHD symptoms and diagnosis. Also, parental ADHD and/or experience of maltreatment could influence the strength of this association. So, we will define and analyse how genetic and social factors affect the association between ADHD and childhood maltreatment, and then how this could be developed through generations. Having assessed and display the association between ADHD and childhood maltreatment, the second study will go a step forward searching the experience of physical abuse and harsh parenting in children with ADHD and children with autism. We will conduct a comparison between children with ADHD and children with autism trying to understand how the different traits of each condition may affect different the risk of physical abuse and harsh parenting.
B4203 - UKDS Non-Communicable Disease Risk Factor Collaboration NCD-RisC - 22/11/2022
Please see associated paperwork in relevant B number folder
B4204 - Intelligence and Religion - 22/11/2022
Religion is an important suite of beliefs and behaviours, yet the factors which cause religious beliefs and behaviours are still largely unknown. One such factor believed to shape religion is intelligence, with previous meta-analyses suggesting a negative association between measures of intelligence and religious belief (Zuckerman et al., 2020). However, the majority of this previous research has been cross-sectional and focused predominantly on American undergraduates, meaning results may be biased by confounding and/or not generalisable to the wider population. We therefore need longitudinal data from population-based studies with repeated religiosity and intelligence data to assess whether these associations may be causal in a more representative population. Enter ALSPAC.
References:
Zuckerman, M., Li, C., Lin, S. & Hall, J.A. (2020). The Negative Intelligence–Religiosity Relation: New and Confirming Evidence. Personal. Soc. Psychol. Bull., 46, 856–868.
B4191 - EWAS of Green Spaces - LifeCycle - 22/11/2022
PLEASE NOTE ALL OF THE FOLLOWING SECTIONS ARE COPIED AND PASTED FROM A PREVIOUSLY APPROVED PROJECT THAT IS IDEANTICAL TO TO THIS - B3549. WE HAVE HAD TO SUBMIT AS A NEW PROJECT TO ACCOMODATE CHANGE TO THIS NOW BINE A PHS MINI PROJECT
The urban exposome (built environment, air pollution, road traffic noise, meteorological, natural space and road traffic) affects health outcomes. For instance, associations between increasing green space exposure and increased birth weight and decreased term low birth weight in 32,000 mother-child pairs have been previously reported (Nieuwenhuijsen et al. 2019).
Here we aim to investigate the epigenetic mechanisms that might mediate this association. We will evaluate the relationship between exposure to green spaces during pregnancy and offspring cord blood DNA methylation at over 450,000 methylation sites (CpG sites) across the genome. This project will contribute epigenome-wide association study summary results to a meta-analysis as part of an ongoing large consortium.
B4196 - Epigenetic pathways to youth self-injurious thoughts and behaviours dissecting phenotypic heterogeneity and time course - 23/11/2022
Suicide is a leading cause of death among youth, but little is known about the associated risk factors. Growing recognition that the existing clinical and psychological measures do not predict suicidal behaviour very strongly has contributed to a focus on the genetic correlates and predictors of suicide risk. Although genotypes do not change across the lifespan, an epigenetic process known as DNA methylation is responsive to environmental experience and can modify the expression of certain genes. Although numerous investigations have cross-sectionally identified a role for DNA methylation changes in self-injurious thoughts and behaviours (such as suicide attempt, suicidal thoughts, and self-injury without suicidal intent), these studies have largely focused on adults. Given that development is associated with numerous biological, epigenetic, and psychosocial changes, there is a need to better identify specific DNA methylation risk factors in youth, rather than extrapolating from work in adults. In this project, we aim to conduct epigenome-wide association studies (case-control comparison of methylation at numerous locations in the genome) of suicide ideation; suicide attempt history; and self-injury without suicidal intent; in teenagers who are part of the Avon Longitudinal Study of Parents and Children. We will also be able to make use of methylation measurements taken in childhood and at birth to trace any methylation differences backward, in an attempt to understand when they might emerge. These findings will be essential to identifying youth-specific risk factors for suicide, and ultimately contribute to efforts to better inform risk assessment as well as biologically informed interventions.
B4197 - Early Life Factors and Childhood Metabolomic Profiles with Risk of Non-Alcoholic Fatty Liver Disease Fibrosis in Young Adults - 21/11/2022
Non-alcoholic liver disease (NAFLD) is the most common cause of liver disease among children and adults. NAFLD is a spectrum of disease which includes significant fat deposits in the liver, liver inflammation, and in some cases permanent scarring and cirrhosis. NAFLD is more common among individuals with obesity and metabolic syndrome. Current evidence suggests risk for NAFLD, obesity, and metabolic syndrome can be inherited and influenced by early life exposures. However, there is no framework for identifying who is at greatest risk for more severe liver disease (inflammation, scarring, cirrhosis). We aim to investigate whether development and severity of NAFLD in young adulthood is associated with blood markers of metabolism in childhood and parental factors.