Proposal summaries
B3996 - Comparison of cellular pattern in nasal lavage induced sputum and Peripheral blood in individuals with asthmamulticenter study - 21/02/2022
B4005 - Does birth weight modify the impact of different weight trajectories on cardio metabolic health in adulthood - 22/02/2022
The change in body weight from infancy to adulthood may impact later cardiometabolic health. In particular, early onset of excess weight gain and long duration of obesity in youth have been associated with an increased risk of cardiometabolic comorbidities in adulthood. High and low birth weight for gestational age, indicating abnormal fetal intrauterine growth, are also associated with an increased risk of cardiometabolic comorbidities in adulthood. There may be an interaction between birth weight and the change in body weight from infancy to adulthood, where the influence of weight gain on cardiometabolic health may depend on birth weight. In the present study, we aim to uncover the independent and combined effects of birth weight and the change in body weight from infancy to early adulthood, on cardiometabolic health in adulthood.
B3994 - Effect of Excessive Weight Gain during Pregnancy on Childrens Neurodevelopment - 22/02/2022
Epidemiological studies found that about 10% of children in the world suffer from neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), Intellectual Disability, Attention-Deficit Hyperactivity Disorder (ADHD) and others. Excessive weight gain during pregnancy appears to be an important factor affecting the health of pregnant women and their offspring. Weight gain during pregnancy changes with gestational age, and the total weight gain during pregnancy may not be able to accurately assess and identify the adverse maternal and infant outcomes. Therefore, it is of great significance to explore the weight changes at different time points during pregnancy. Further, the mechanism mediating the association between weight gain during pregnancy and childrens' neurodevelopmental disorders is still unclear. Epigenetic mechanisms may play an important role. This study will test the hypothesis that excessive weight gain during pregnancy may cause fetal epigenetic changes, affect the growth pattern of offspring, affect the brain development of children, and increase the risk for neurodevelopmental disorders in children.
B4006 - UK LLC Twitter use as a mental health phenotype during the COVID-19 pandemic - 28/02/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4003 - CAMCOG collection of cognitive data - 28/02/2022
Cognitive data will be collected from both generations of ALSPAC using CamCog (Cambridge Cognition). This will be linked to the next ALSPAC COVID questionniare which is likely to go out just after Easter 2022.
B4002 - Pathway to psychosis among cannabis users - 28/02/2022
Mendelian randomisation studies have not yet clarified the direction of causality between heavy cannabis use and Schizophrenia. Thus, while cannabis use remains the most preventable risk factor for psychotic disorders, it is still unclear what makes some heavy users more susceptible to develop clinical psychosis. This is a question of global relevance with the spreading of laws legalising cannabis use for medicinal and/or recreational purposes.
Recently, epigenetic processes that regulate where our DNA is expressed, have been implicated in both psychotic disorder and substance use. Indeed, genome wide DNA methylation (DNAm) studies (EWAS), which measures where the DNA is switched on or off, have become a tool to look at the biological effects of environmental exposures.
This proposal, nested within a larger MRC Senior Fellowship project, focuses on the development of a genome wide DNAm score associated with regular cannabis use, taking into account both genetic factors and other environmental exposures. These analyses will run in parallel to mouse model experiment of exposure to both THC and CBD (cannabidiol), the most studied ingredient of cannabis. Finally, we plan to examine overlaps in the effect of cannabis compounds on the brain of mice with the effect in human blood tissue, to begin to understand a) the neurobiology of psychosis in the context of heavy cannabis use and b) to build epigenetic and genetic scores that might help distinguish those cannabis users that come to no harm from those who develop a) sub-clinical psychotic experiences paranoia and b) frank clinical psychosis.
B3917 - Gene-gene gene-enviroenment interaction and risk prediction of pediatric mental disorders multi-omics data analysis of ALSPAC - 17/02/2022
Growing evidence shows that the environment exposure and molecular level of maternal conditions might affect mental health of children; However, the relationships remained elusive. In this project, we aimed to study the interaction effects between genes and genes (G×G), genes and environments (G×E), as well as environments and environments (E×E). Furthermore, by combining both main effects and interaction effects of genes and environments, we want to construct a prediction model for children depression.
B3990 - Understanding developmental trajectories of risk and resilience amongst children who experienced adverse childhood experiences - 21/02/2022
Children who experience adverse childhood experiences (ACEs) are at greater risk for psychiatric disorders, chronic health diseases, and poor educational and social outcomes. Experiencing ACEs such as abuse, neglect or bullying in childhood increases vulnerability to poor developmental outcomes, yet not all children who experience such adversity go on to develop adjustment difficulties. Sources of resilience exist on multiple levels: individual characteristics including biological predisposition and psychological coping styles; physical, economic and social capital offered to children and caregivers; psychosocial interventions by mental health, social welfare, and education providers; and government policies that prioritise or neglect maltreated children. This project will integrate methods from social epidemiology and developmental psychology to understand the trajectories of risk and resilience amongst children who experienced ACEs, by using longitudinal analysis and advanced statistical methods to examine risk and protective factors at the individual, family, school and community level. Findings will inform intervention strategies and policies aimed at promoting resilience amongst vulnerable children.
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.
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.
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.
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.
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.
B3998 - Development of anxiety and depression in young people explaining individual and cross-cohort differences in risk outcomes - 22/02/2022
Adolescence is marked by rapid social and biological change and a sharp rise in the incidence of depression and some forms of anxiety. Youth anxiety and depression are typically foreshadowed by earlier childhood difficulties and exposure to multiple adversities; additionally, there are far-reaching consequences for outcomes in adulthood – for education and employment, relationships with others, and physical and mental health. Young people today are also more likely to experience anxiety and depression than previous generations.
There is substantial variability in the developmental course of depression and anxiety, with our own research showing distinct developmental pathways leading to depression, and differences in outcomes. For example, some children show chronic or escalating mental health difficulties; others (even those at high risk) do not develop anxiety and depression. Understanding when, how and in whom to intervene to reduce risk is important to prevent anxiety and depression and to improve outcomes. We aim to identify early predictors of risk (social, clinical and genetic), consider protective mechanisms that build mental health resilience and optimise outcomes, and test the causal role of identified risk and protective factors.
Through comparison with other cohorts, we will test the extent to which findings generalise, and what the reasons are for increases in youth depression and anxiety in more recent generations of young people.
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.
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.
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.
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.
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).
B3991 - Exploring the determinants and consequences of eating architecture - 17/02/2022
This PhD project aims to study the underlying relationship between eating architecture (initially understood as size, timing and frequency of eating, but intended to be expanded to other aspects of nutrition such as dietary patterns, macronutrients and food preference) and adiposity-related traits in the population.
Exploring the determinants of nutrition-related behaviours, especially related to obesity – currently one of the major public health problems of the westernized world – may contribute to the understanding of the complex interactions between genetics, physiology, environment surrounding people’s eating behaviours.