Proposal summaries
B4526 - THE PLACENTA IN MATERNAL AND FETAL CARDIOVASCULAR HEALTH AND DISEASE - 12/02/2024
The placenta is the crucial interface between mother and developing fetus during pregnancy, enabling exchange of nutrients, oxygen, and waste products. The placenta is essential for a healthy pregnancy; placental pathologies underlie some of the most common pregnancy complications, referred to as placental syndromes (PS). PS include hypertensive disorders of pregnancy (preeclampsia and gestational hypertension), fetal growth restriction, and preterm delivery, which are leading causes of maternal and neonatal mortality and morbidity. PS are associated with adverse cardiovascular health beyond delivery and throughout life, both in the mother and offspring. Yet the placenta remain understudied and the mechanisms linking PS, congenital heart disease in offspring and cardiovascular health in both mothers and offspring are not well understood. In this project we aim to understand the the basis for primary placental disorders as the cause of secondary heart and vascular disease, both in the offspring and in the mother.
B4500 - The additional effect of paternal mental health on early childhood neurodevelopment - 31/01/2024
Accumulating data from epidemiological and molecular studies indicate that adverse early childhood neurodevelopment is a risk factor of neuropsychiatric illness in later life. Among several factors that can affect early childhood neurodevelopment, maternal health, including both her physical and mental health, have been convincingly identified as predictors of children’s neurodevelopment. However, the evidence concerning the additional effect of paternal mental health on the child`s neurodevelopment is sparse warranting further research in this area. This research fits in the Paternal Origins of Health and Disease concept (POHAD).
B4513 - International Multicohort Pediatric Biomarker Collaboration Biomarkers4Pediatrics - 12/02/2024
Health monitoring and clinical decision making in paediatric care largely depend on the availability of reference values for clinical parameters. Hence, the diagnosis of highly prevalent conditions in children and adolescents such as metabolic dysfunction has been hampered by the lack of a worldwide consensus on diagnostic criteria, as definitions and cut-offs being used in the paediatric population are frequently derived from the adult population. Providing globally applicable reference curves for the metabolic syndrome and its components, in early life - from birth to adolescence - represents a big step towards the ultimate goal: developing cut-offs for clinically relevant biomarkers for paediatric practice. By making use of the increasing availability of research data worldwide, we aim to establish a global pooling initiative building on a previously published special issue of the International Journal of Obesity "Filling the gap: international reference values for health care in children" (edited by Ahrens W, Moreno LA, Pigeot I), and further taking advantage of increased statistical power and variations across age groups, geographical regions and socio-cultural backgrounds. Thus, biomarker data for the metabolic syndrome are being collected, subsequently calibrated, harmonized, combined and analysed to provide age-, sex- and ethnic-specific reference curves for metabolic biomarkers to facilitate the diagnosis of metabolic syndrome in early life globally.
B4514 - Urban exposome and body mass index trajectories from birth to adolescence - 06/02/2024
This project will investigate whether the environment in which children live affects their likelihood of becoming overweight or obese as they grow up.
There is evidence that some factors of the urban environment, such as air pollution and whether the street design encourages walking, are linked to body mass index in children. There is a need to build on this evidence though, by considering how different factors might interact with each other, for example if a person lives near a busy road they will be exposed to noise and air pollution from it, so it is important to determine whether these factors are both related to body mass index, or whether it is one or the other. We will also investigate whether characteristics of individual people, like age and socio-economic status, affect the relationships found in previous studies.
This project will use height and weight measurements collected from children in the ALSPAC study and combine them with information on the environment in which they live, for example air pollutant levels, the amount of green and blue space, and the amount of public transport. We will use this information to determine whether the environment in which a child grows up affects their likelihood of becoming overweight or obese in later life, and also whether there are interactions between these factors. Understanding how these factors might affect overweight and obesity in childhood, and how it progresses into adolescence, is important for identifying communities that may be at increased risk, and to provide information that local communities may wish to use to address any relevant risk factors.
B4517 - Early metabolic and proteomic features of endometrial cancer - 22/01/2024
Cancers develop for many years before they are diagnosed. Using data from first-generation ALSPAC offspring, we aim in this study to estimate the effects of being more genetically susceptible to endometrial cancer on metabolic and proteomic traits measured in blood across early life; this should help to reveal what early stages of endometrial cancer development look like and when they occur. More specifically, we will examine associations of genetic risk scores for endometrial cancer that has been shown to be influenced by obesity with traits from targeted metabolomics measured in childhood (age 8y), adolescence (age 15y), and young adulthood (age 18y and 24y) and proteomics measured in childhood (age 8 y) and young adulthood (age 24). This allows us to view subtle changes in the circulating metabolome and proteome over time which precede the onset of clinically detectable endometrial cancer by several decades. Recognizing the early signs of endometrial cancer development is vital for informing early detection, preventing its onset in older age, and improving survival.
B4520 - Genetics of anorexia nervosa and associations with physical and psychological dimensions of childhood development - 22/01/2024
Anorexia nervosa (AN) has the highest mortality out of all psychiatric conditions, early onset (between 12-15 years), and long-term health issues. Although the exact cause of AN is not yet fully understood, it is known that a complex combination of environmental and genetic factors plays a role in its development. Genetics alone are estimated to explain 50 to 60% of risk for AN. Recently, a large-scale genome-wide association study (GWAS) identified eight genomic regions associated with AN, as well as evidence that the genetic architecture of AN overlaps that of metabolic and anthropometric traits, such as body-mass index (BMI) and risk for type-2 diabetes. In this study, we will analyze AN GWAS results to compute polygenic risk scores (PRS) for ALSPAC participants, allowing us to estimate the genetic risk for AN for each participant. We will test how genetic risk for AN is associated with behavioural and emotional problems during childhood and whether these associations are development-specific by modeling psychopathology measures longitudinally. We will also test associations between AN and physical growth during early life. Given the patterns of genetic associations between AN and BMI, we will test whether genetic risk for AN that has been adjusted for genetic correlations with BMI affects previously identified associations.
B4519 - UKLLC Investigating the association of long-term air pollution exposure with risk and severity of SARS-CoV-2 infection - 22/01/2024
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4516 - CC16 in childhood and resilience to airflow limitation in young to mid-adult life - 21/02/2024
Club cell secretory protein (CC16, also known as CC10, CCSP, and uteroglobin) is a homodimeric pneumoprotein encoded by the SCGB1A1 gene that is mainly produced by club cells and other airway epithelial cells but can be readily measured in circulation. A growing body of evidence indicates that this molecule plays a critical role in enhancing resilience to respiratory infections and reducing airway inflammation. In this context, our hypothesis is that low levels of circulating CC16 in childhood may serve as an early indicator of individuals who will develop airflow limitation, a precursor of early chronic obstructive pulmonary disease (COPD), in their young adult life. Because of the expected low prevalence of airflow limitation in young adult life, testing this hypothesis will require a large epidemiological consortium of birth cohorts that have serum/plasma samples available from childhood and have characterized the lung function of a large number of participants from birth into adult life.
Here we propose to measure CC16 levels in plasma samples collected at ages 7, 9, and 15 years from ALSPAC participants to determine whether deficits in circulating CC16 in childhood predict the development of airflow limitation and small airway disease, as precursors of early COPD, in young adult life. We will integrate multiple longitudinal measurements of CC16 in childhood and link them to lung function measurements (both spirometry and IOS) completed in adult life.
B4518 - Social psychological cognitive and biological mechanisms underlying the impact of early life adversity on anxiety-related dis - 31/01/2024
Adverse childhood experiences (ACEs, e.g. family violence, parental mental health problems, bullying) carry a higher risk of anxiety-related disorders, yet the underlying mechanisms remain unclear. We will use cohort studies in the UK and Brazil to assess the mechanisms linking ACEs to anxiety-related disorders.
The depth and breadth of measurements in the cohorts enables us to examine: 1) multiple levels of explanation: social, cognitive, psychological, biological, plus within- and between-level interactions, 2) the developmental trajectory of onset and persistence of anxiety, and how this can be prevented or interrupted, 3) the role of commonly co-occurring conditions (e.g. depression, neurodivergence), and 4) consistency/specificity of mechanisms across ACEs and anxiety-related disorders.
Comparisons across generations and the UK and Brazil, where social contexts and levels of ACEs vary, will enable assessment of the degree to which interventions need to be culturally/generationally specific.
Multiple analysis approaches will support causal inference: difference-in-difference, sensitivity analyses to assess environmental and genetic confounding, and causal mediation analysis. Where possible, we will triangulate cohort analyses with Mendelian randomization studies using large biobanks.
The research has been co-designed, and will be co-produced by, UK-based people with lived experience of anxiety. We will develop and evaluate lived experience involvement in Brazil.
B4515 - What determines the risk of type 1 diabetes in antibody positive adults - 29/01/2024
Type 1 diabetes occurs when a persons immune system attacks their pancreas stopping them producing insulin. The only current treatment is insulin replacement. Recently a new treatment has been found, which delays the onset of type 1 diabetes giving people more years without insulin. This exciting new treatment can only be given to people before they have diabetes symptoms. To date all research into how to find these early cases has been in children. You can detect early cases by testing children for markers of the immune attack called antibodies. Based on the number and type of these antibodies we can predict a child’s future type 1 diabetes risk and if they will benefit from the new treatment. Half of type 1 diabetes develops in adults but we do not know an adults future type 1 diabetes risk if we find antibodies and thus who needs treating. This study aims to answer this question by looking for antibodies in adult blood samples taken over 5 years ago. We will recontact all adults with antibodies in these old samples and some people without (controls) asking for a finger prick sample (taken at home or in hospital) to measure their antibodies and blood glucose level now. We will also ask if they have developed diabetes and their treatment and diabetes type if they have. This study will allow us to screen for antibodies in adults and predict those most likely to develop type 1 diabetes and therefore benefit from new treatments.
B4492 - DNA methylation profiling by capture sequencing - 23/01/2024
DNA methylation is the addition of a methyl group to DNA. Patterns of DNA methylation have a variety of roles cells, the most well-known is determining the activity of genes. These patterns are known to change in response to lifestyle factors such as cigarette smoking and diet and to be useful in diagnosing disease and predicting future disease risk. Measuring patterns of DNA methylation is challenging as there are about 28 million locations in the human genome that can be methylated. Fortunately, we can obtain useful information about health from a small subset of these locations. A new method for cheaply measuring a small, selected subset uses a system that captures DNA fragments containing specific nucleotide subsequences and then measures the methylation patterns on those fragments by DNA sequencing. A couple of ALSPAC DNA samples have had DNA methylation measured using more expensive methods (beadchip and nanopore sequencing). We would like to evaluate the performance of our new method by applying it to these samples and then comparing the results to these other methods.
B4509 - Investigating the association between romantic relationships and experiences of psychosis over time - 15/01/2024
Psychosis refers to the experience of hallucinations and/or delusions. Psychotic experiences range from short-lived symptoms that are not fully believed through to persistent severe symptoms that characterise psychotic illnesses such as schizophrenia. Compared to the general population, the prevalence of romantic relationships in people who experience psychosis is low. This is problematic. Firstly, because people with psychosis, like members of the general population, see romantic relationships as being a fundamental aspect of life and often report being dissatisfied with their intimate relationships. Secondly, because there is some evidence to suggest that having a partner is associated with reduced symptoms for people who experience psychosis, especially for those under 35 years old.
Unfortunately, much of the available literature is limited and as a result, the direction of influence between romantic relationships and psychosis remains unclear. This project aims to use data collected at various timepoints to better understand whether being without a partner increases vulnerability to developing psychosis / contributes to the maintenance of symptoms, or if those who experience fewer symptoms are simply more able to form romantic relationships.
B4511 - Hypertensive disorders in pregnancy and risk of ADHD in offspring - 15/01/2024
Attention Deficit Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental condition, characterized by difficulties in behavioural and neurocognitive functioning. Many studies have suggested that some maternal factors during pregnancy are associated with ADHD in the offspring. However, the mechanisms and whether the associations are causal is still unclear. This project will be conducted to understand the impacts of maternal hypertensive disorders during pregnancy on attention deficit hyperactivity disorder (ADHD) in offspring as little is known about this. As ADHD is becoming more prevalent, more research is needed to thoroughly understand factors that may increase risk of this disease. We will investigate the role of hypertension during pregnancy in ADHD using genetic, clinic and questionnaire data from the ALSPAC cohort.
B4512 - Examining the association between religiosity and substance use - 15/01/2024
Previous studies have found that greater religious belief is associated with lower risk of substance use, however these studies are limited in their samples and measures used. We wish to examine whether (non)religious belief is associated with substance use (smoking, drugs, alcohol) in adolescence, while controlling for a number of confounding variables.
B4502 - Sleep problems in adolescence as a risk factor for mental health problems in young people-Part 1 - 08/01/2024
Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.
B4503 - Sleep problems in adolescence as a risk factor for mental health problems in young people-Part 2 - 08/01/2024
Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.
B4504 - Sleep problems in adolescence as a risk factor for mental health problems in young people-Part 3 - 08/01/2024
Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.
B4505 - Sleep problems in adolescence as a risk factor for mental health problems in young people-Part 4 - 08/01/2024
Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.
B4506 - Sleep problems in adolescence as a risk factor for mental health problems in young people - Part 5 - 08/01/2024
Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.
B4507 - Sleep problems in adolescence as a risk factor for mental health problems in young people - Part 6 - 08/01/2024
Sleep is a critically important behavior, although we still do not fully understand it. A substantial body of evidence indicates that an appropriate level of sleep is necessary for optimization of physical, cognitive, and emotional functioning. In other words, sleep is crucial - it is as important to our bodies as eating, drinking and breathing, and is vital for maintaining a good mental health. In other words, sleep is a key aspect when exploring mental health problems. However, there are still a number of unanswered aspects in this area of research. For example, it is still unclear whether sleep is prospectively related to a wide range of mental health problems (e.g., anxiety, depression, psychosis), or whether it is more relevant in certain areas. Further, it is unclear how sleep prospectively associates with mental health: are there specific underlying mechanisms or contributing factors explaining these prospective associations? The relevance of understanding the role that sleep plays in the development of subsequent mental health problems lies in the possibility of designing future intervention strategies in mental health, where intervention in sleep would be one of the main focuses, to prevent the development of future mental disorders.
Therefore, the current project will involve investigating how sleep problems in adolescence prospectively associate with several mental health problems in young adulthood, and determining which is the role of relevant factors, including environmental, family, or cognitive factors in these prospective associations. To do this, we will use secondary data analyses, using the Avon Longitudinal Study of Parents and Children (ALSPAC), which comprises around 14,000 individuals recruited at birth. Risk factors to be investigated in this study include sleep patterns in adolescence (15 years old), such as sleep duration, bedtime, sleep fragmentation or sleep onset latency. Further, we will focus on a range of mental health outcomes at the age of 24 years old as the dependent variables, including depression, anxiety, psychosis, or self-harm. Finally, we will include number of potential covariates in these analyses, such as family factors, socio-economic status, social factors of cognitive factors.