Proposal summaries
B3983 - The effects of maternal antenatal fatigue and stress on maternal and offspring mental health - 17/02/2022
Maternal fatigue is common during pregnancy, but knowledge on predisposing factors is scarce, and research on the effects of maternal antenatal fatigue on maternal mental health and offspring mental health is lacking. We will study factors associated with maternal fatigue in a cross-sectional setting. Secondly, we will study if maternal fatigue associates with mental health in the offspring. In both settings ALSPAC will be used as replication sample for findings in the Northern Finland Birth Cohort 1986 (NFBC1986).
B3993 - Use of a polygenic risk score to stratify for treatment for extreme short stature - 17/02/2022
Children with idiopathic short stature (ISS) are defined by height below 2 standard deviations (SD) of the mean for age and sex without any endocrine, metabolic or other disease explaining the short stature. Recently the US Food and Drug Administration has approved Vosoritide for individuals with extreme short stature which is caused by a single gene mutation.
However, there are causes of extreme short stature that are not due a single gene mutation. These include polygenic predisposition to disease. We have recently generated a polygenic risk score that can reliably predict adult height, and this was tested in the ALSPAC cohort. We hypothesize that children who are extremely short due to a polygenic cause may also benefit from Vosoritide therapy.
Therefore, we posit that a polygenic risk score can help to identify children at extreme short stature. It could also help to predict if Vosoritide therapy could be helpful, by assessing if genetic changes in the biological pathway that is influenced by Vosoritide influences height. Last, we can use this polygenic risk score to better understand if extreme short stature is associated with other diseases and medically-relevant traits.
B3974 - The intergenerational transmission of religiosity - 14/02/2022
Children often—but not always—retain the religious identities, beliefs, and practices of their parents. This project aims to find patterns in what we call “intergenerational religious transmission”, with a particular focus on parents’ religious denominations, their own religious beliefs and behaviours, their intentions to raise their children in their religious traditions, and their children’s religious beliefs, behaviours, and attitudes during childhood. A secondary purpose is to test the “religious residue” hypothesis over time, which contends that religious deidentifiers still maintain aspects (i.e., residue) of their former religious identities.
B4001 - The role of parental religiosity in offspring mental health - 14/02/2022
There is limited evidence for the role of parental religious beliefs in offspring mental health, with the existing literature predominantly concerned with American samples, and a limited number of mental health outcomes. This project seeks to examine the role of parental religious beliefs, and how they may predict offspring mental health in childhood and adolescence. This will be done using a broad range of mental health measures, and possible confounding, mediating, or moderating variables.
B3997 - Investigating links between regulatory T cell depletion and mood and psychotic symptoms - 14/02/2022
Immune dysregulation is thought to be involved in psychiatric disorders, including psychotic and mood disorders (1). Regulatory T cells (Tregs), an important component of the immune system, may have a role when investigating the causes of disorders such as anxiety, depression and psychosis. For example reduced number of Tregs have been found in individuals with disorders including schizophrenia, postpartum psychosis and major depression (2-4). However, the role of immune dysregulation in mood and psychotic symptoms in the general population has not been investigated. Through ALSPAC, we will investigate whether Treg sensitive genes are more common in individuals who have reported mood and psychotic symptoms, including post-partum depression. In combination with follow up experiments, this project will help us understand whether immune dysregulation is a risk factor for mood and psychotic symptoms.
B3932 - Examining the latent structure of ALSPAC RSBB variables - 14/02/2022
There are a variety of ways to measure religious beliefs. However, there is evidence that some commonly used measures of religiosity function poorly for atheist and spiritual individuals. In the ALSPAC there are a several measures of religiosity based upon pre-existing scales, such as the Duke University Religion Index (DUREL) and the Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS). The aim of the current study is to examine the latent structure of the items taken from these scales, for use in ALSPAC, and to explore whether these items are measurement invariant across religious, atheist and spiritual individuals. This will provide an insight into the way religiosity is measured in ALSPAC and inform future scale construction using these items.
B3989 - Epigenetics of changing traits - individual EWAS linked to B3967 - 14/02/2022
The last decade has seen a dramatic improvement in our understanding of how our genes affect our height, body mass index (BMI), mental health, cancer risk, and many other traits. This has been facilitated by technological developments which allow us to measure a persons’ epigenetic data accurately and economically. Almost all epigenetic studies investigate traits collected at a single timepoint (e.g. adult height), and the epigenetic sites associated with these traits are then found using an epigenome wide association study (EWAS). However, some traits such as BMI change over time, and the epigenetics of these repeatedly measured traits remain poorly understood. This project will apply new approaches for epigenetic analysis of longitudinal traits - in particular BMI measured repeatedly from birth to adulthood and depressive symptoms from later childhood through adolescence.
B3988 - Exploring the suicidal drive hypothesis for psychosis - 14/02/2022
A recent suicidal drive hypothesis posits that psychotic experiences (PEs) may serve to externalize internally generated and self-directed threat (i.e., self-injurious/suicidal thought/behavior [SITB]) in order to optimize survival. Preliminary investigations have attempted to demonstrate that such internal threat can both precede and inform PEs. To date findings derived from analyses of cross-sectional epidemiological data, national prospective cohort/service use data, and, prospective twin cohort data have indicated that SITB is indeed predictive of PEs. This study seeks to explore the hypothesis further.
B3787 - The effect of timing and cessation of maternal smoking upon the DNA methylation score - 14/02/2022
The smoking score was developed in the Raine Study (partner: University of Western Australia/Telethon Kids Institute, Perth, Western Australia) and the Northern Finland Birth Cohorts 1986 and 1966 (partner: University of Oulu, Oulu, Finland). For the score development, DNA methylation data measured with the Illumina HumanMethylation450 BeadChip array was utilized, together with a binary variable, indicating if the study participant’s mother was smoking during pregnancy.
Our hypothesis is that the smoking score captures and quantifies latent information on early life exposure. We also hypothesize that it quantifies the persistent changes that occur systemically in the offspring with maternal smoking exposure in utero.
B3984 - Long-Term Occupational Implications of Preschool Gender-Related Play Behaviour - 14/02/2022
Globally, there are substantial gender gaps in occupations. Men are overrepresented in leadership and managerial positions, as well as in science, technology, engineering, and mathematics (STEM) fields, whereas women are overrepresented in administrative and assistant positions, as well as in education and social welfare fields. Similar gender differences are evident in the UK, where men represented 66% of parliament members in 2019 (UK Parliament, 2020), 67% of leadership board members across the top 350 companies listed on the London Stock Exchange in 2020 (FTSE Women Leaders, 2021), and 73% of the STEM workforce in 2019 (British Science Association, 2020), whereas women represented 72% of school teachers, 86% of nurses, and 92% of secretaries in 2018 (UK Office for National Statistics, 2018).
The developmental approach is underused in existing high-level strategies designed to tackle the gender gaps, although the roots of these gaps can be traced back to early childhood. Crucially, aspects of childhood play show some of the most substantial behavioural gender differences in human development. It has been proposed that male- and female-typical play are qualitatively different and differentially contribute to the development of personal characteristics and gender-related socio-cognitive processes (Kung, 2022). Recently, using ALSPAC data, Kung (2021) has provided the first evidence that preschool gender-related play behaviour longitudinally predicts gender-related occupational interests in adolescence. Nonetheless, it remains unknown whether childhood play contributes to actual occupational choices in adulthood.
This proposed study will test the relationship between preschool gender-related play behaviour and gender-related occupations in adulthood.
KEY REFERENCES
Kung, K. T. F. (2021). Preschool gender-typed play behavior predicts adolescent gender-typed occupational interests: A 10-year longitudinal study. Archives of Sexual Behavior, 50, 843–851.
Kung, K. T. F. (2022). Gender differences in children’s play. In P. K. Smith and C. H. Hart (Eds.), The Wiley-Blackwell handbook of childhood social development (3rd ed.). Chichester, UK: Wiley-Blackwell.
B3987 - Validation of the Our Future Health genotyping assay - 25/04/2022
Our Future Health will collect information from up to 5 million volunteers from across the UK to create one of the most detailed pictures we’ve ever had of people’s health. Researchers will be able to use this information to discover more effective ways to prevent, detect and treat diseases. As part of the programme, genetic information will be extracted from blood samples collected from the volunteers, using a new genetic test which will give information on over 600,000 genetic variants (DNA which may vary from person to person). Before it can be used, however, the test will require preliminary accuracy checks and other comparisons on a collection of samples where the correct genetic information is already known. We propose to conduct these checks on a set of 1800 samples from the ALSPAC cohort, which have established cell-lines for DNA extraction and whole genome sequence information as part of the UK10K programme. These samples will be tested by the supplier of the genetic test, and the results sent to Our Future Health for comparison against the reference genetic information. For any genetic variants that do not meet our pre-specified level of accuracy, this part of the test will be re-designed by the supplier and the assessments repeated. This work will help to ensure that the Our Future Health genetic tests are as accurate as possible, and through the Our Future Health programme will contribute to research to prevent, detect and treat disease for decades to come.
B3981 - Parental age and offspring DNA methylation - 07/02/2022
Advanced parental age has been associated with adverse offspring health outcomes, but the biological mechanisms underlying these associations remain unclear. Research suggests that epigenetics may play a role, especially since advanced parental age has been associated with lower levels of offspring DNA methylation, which in turn, have been associated with adverse offspring outcomes. Nevertheless, the association between advanced parental age and epigenetics has only been explored in two studies with relatively small sample sizes. Larger epigenome-wide association studies are required to identify more CpG sites and improve our understanding of epigenetic mechanisms underlying the observed associations between advanced parental age and adverse offspring health outcomes.
References:
1. Adkins RM, Thomas F, Tylavsky FA, Krushkal J. Parental ages and levels of DNA methylation in the newborn are correlated. BMC Med Genet. 2011;12:47.
2. Markunas CA, Wilcox AJ, Xu Z, et al. Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. PLoS One. 2016;11(7):e0156361.
3. Pinheiro RL, Areia AL, Mota Pinto A, Donato H. Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis. Acta Med Port. 2019;32(3):219-226.
4. Ryer EJ, Ronning KE, Erdman R, et al. The potential role of DNA methylation in abdominal aortic aneurysms. Int J Mol Sci. 2015;16(5):11259-11275.
B3978 - Genome-wide association study of bone mineral density in ALSPAC children and mothers - 04/02/2022
Osteoporosis is a common age-related condition with a strong genetic component. Osteoporotic fractures significantly contribute to disease burden and costs. Whilst a number of genes responsible have been identified, many gene variants each contribute to the disease but each with subtle effect.
Previous GEnetic Factors for OSteoporosis Consortium (GEFOS) study identified a number of BMD-related loci using a genome-wide association study (GWAS). As part of this collaboration, an ongoing meta-analysis of four DXA-derived BMD traits is being conducted. Cohorts previously involved as well as new and updated cohorts are being invited to take part in this effort.
B3986 - Early Environmental quality and life-course mental health effects - Equal Life - 15/02/2022
Air pollution, road transport noise and other environmental exposures in pregnancy and early life may affect many aspects of a child's development and have long-term effects tracking into adult life. However, there are few studies on the impact of very early life exposures to environmental pollution. This study will focus on effects of environmental exposures in early life on mental health and cognition in childhood. The analyses will form part of a large European study with over 30 participating institutions. The answers will help develop environmental policies to protect children's health and development.
B3985 - Uncovering novel early life risk factors and molecular markers for cancer prevention - 09/02/2022
Cancer is a leading cause of morbidity and mortality worldwide. Its burden is expected to increase in the coming years as populations age and increase their exposure to unhealthy lifestyle factors. Most research on cancer aetiology has been conducted in adult populations. This has led to the identification of well-established risk factors in adulthood, such as smoking and obesity. Nevertheless, it is still unclear whether cancer risk may be influenced by early life exposures. Furthermore, the mechanisms by which early life exposures may influence cancer risk have not been fully elucidated. They possibly involve inflammation, changes in the microbiome, metabolism, insulin resistance, hormonal factors and epigenetic modifications. Therefore, the aim of this project will be to identify novel early life risk factors and molecular markers for the prevention of cancer.
B3976 - Is the Bike Drawing test a useful indicator of brain-related visual function in ALSPAC participants - 31/01/2022
I am PI for an exsting project (B3770) which uses ALSPAC data to explore whether a seletion of candidate genes (known to influence the brain's ability to respond to injury) are related to the presence or absence of brain-related vision problems.
In this add-on project, a medical student will examine some additional data from ALSPAC, to see whether the results of a task (the Bike Drawing task; BD) the ALSPAC children carried out at age 11 are in agreement with the results of the brain-related vision tests already requested and in use in B3770. The BD task is an adaptation (for ALSPAC) of a standard neuropsychology assesment called the Rey Osterrieth Complex Figure Test (ROCFT), which assesses visuoconstructive skills and visual memory. This project will therefore be a learning exercise for the student and will provide useful preliminary data as to whether the BD task may be useful in clinical paediatric ophthalmology practice.
B3977 - Estimate the causal effect of maternal smoking during pregnancy on offsprings birth weight using ALSPAC data - 04/02/2022
Numerous studies have shed light on the effects of maternal smoking during pregnancy on the offsprings’ health outcomes. In particular, maternal smoking during pregnancy was found to be associated with lower offspring birthweight. Previous studies normally address confounding by adjusting for maternal age, socioeconomic status, breastfeeding and offspring gender. However, concerns about unmeasured confounding biases due to the mother’s lifestyle, the households’ socioeconomic status, and mother’s genotypes still remain.
The negative control method is a recently popularized approach that utilizes measured covariates as proxies of unmeasured confounders, in order to detect, reduce and correct for confounding bias. This method may help eliminate the confounding bias when studying the causal effect of maternal smoking on child birth weight. For example, paternal alcohol consumption during the mother’s pregnancy can serve as a potential negative control variable since it’s a proxy of the household’s socioeconomic status but shouldn’t directly affect the offspring’s birth weight. Therefore, any observed association between paternal alcohol consumption and the child’s birth weight is likely a result of confounding bias. Other negative control variables may include negative control exposures (NCEs) such as mother’s smoking behavior after giving birth, and negative control outcomes (NCOs) such as the child’s injuries since age 9.
In this project, we will utilize multiple negative control variables to obtain a more accurate estimate of the causal effect of maternal smoking during pregnancy on infants’ birthweight with the ALSPAC data.
B3982 - Maternal metabolic risk factors and prognosticators for offspring affected by congenital heart disease - 07/02/2022
Congenital anomalies complicate over 2% of births, with congenital heart disease (CHD) the most common accounting for approximately one third. However, understanding of potential causes is limited, with only 20% related to known genetic, chromosomal or teratogenic factors. Greater knowledge of maternal risk factors and causative mechanisms is essential. Assessing the maternal metabolome offers an opportunity to achieve these goals. Metabolomics describes the study of small molecules and substances created by the processes of the body. It reflects how the body functions and is influenced by genetics, our environment and other factors such as health conditions and pregnancy. This project will perform large scale metabolomic analysis utilising the Children-OMACp, ALSPAC and Surgical-PEARL cohort studies based in the South-West of England. Firstly, case control study will compare metabolomic profiles of non-pregnant mothers of children with CHD to controls with no congenital anomaly. Further study will then compare metabolomic profiles in pregnant mothers of fetuses with CHD and controls with no congenital anomaly. This research aims to elucidate potential maternal metabolic risk factors and causative pathways for fetal CHD. It will also allow us to greater understand the role the fetus has in influencing maternal metabolomic profiles in pregnancies complicated by CHD. This can be compared to underlying maternal metabolic variation that could represent a causative pathway for fetal CHD. This understanding could revolutionise care for women before and during pregnancy. Furthermore, it offers an exciting opportunity for primary prevention of CHD.
B3956 - Investigating the effects on happiness life satisfaction and meaning in life following the transition to parenthood - 27/01/2022
The project will investigate the impact that the transition to parenthood has on wellbeing. In particular, the project will focus on understanding how becoming a parent impacts individuals’ happiness, life satisfaction and meaning in life using a longitudinal design.
Research investigating the impact of parenthood on wellbeing produces mixed findings. Some findings indicate that parenthood is associated with detrimental effects on wellbeing (Stanca, 2012), whilst others have suggested that parenthood is associated with improved aspects of wellbeing (Nelson et al., 2013). However, the research investigating the effects of parenthood on wellbeing is difficult to summarise, due to the varying definitions of wellbeing that are used within the literature and the different means of operationalising the term. For example, studies have measured wellbeing by examining symptoms of depression, alcohol abuse, happiness, life satisfaction and frequency of positive and negative emotions. Therefore, this study aims to look at how parenthood effects different aspects of wellbeing individually as there may be differential effects of parenthood on happiness, life satisfaction, and meaning in life. Prior studies have found that parents have higher levels of meaning in life than non-parents (Nelson et al., 2013). However, there are more mixed findings regarding happiness and life satisfaction (Umberson & Gove, 1989). Therefore, the findings regarding the relationship between parenthood and wellbeing do not represent one construct and making concluding statements about parenthood and wellbeing would fail to acknowledge the discrepancies among how wellbeing has been measured and defined.
Previous research has suggested that the relationship between parenthood and wellbeing differs depending on gender, relationship status and financial strain on the parent. It has been reported that mothers experience poorer wellbeing in comparison to fathers (Nelson et al., 2019). Parents who are married may have better wellbeing in comparison to single parents because of the proposed benefits such as division of labour in the home and for parenting tasks (Cunningham & Knoester, 2007). Stanca (2012) also reported that parenthood negatively impacts life satisfaction due to a lack of financial satisfaction and increased financial strain associated with parenthood. Whether the individual is a first-time parent may also be important to investigate because experiences of parenting might not match prior expectations with consequences for mental health in new parents (Harwood et al., 2007).
B3957 - Investigating the impact of anxiety on coping strategies during a pandemic - 27/01/2022
The unprecedented national lockdowns in 2020/21 in response to the COVID-19 pandemic gave many reasons for people to experience increased levels of stress and anxiety driven by potential factors such as fear of illness or death, social isolation, losing jobs and loss of autonomy. To manage the negative experiences of situations like this, people commonly engage in coping strategies to reduce their perceived stress. Potential coping strategies include engaging in exercise, changes in eating, drinking and smoking patterns, social interaction and engagement with news, media reports and conversation related to the pandemic.
We aim to investigate whether there is a relationship between the level of anxiety experienced early in the first UK lockdown and participants subsequent coping behaviours. Did those with higher levels of anxiety at the start of lockdown engage in different coping strategies to those less anxious? Furthermore, how does engaging in certain coping strategies impact levels of anxiety later in the pandemic? Through this further investigation, inferences can be made about how well certain coping strategies work for individuals with different levels of anxiety.