Proposal summaries
B4024 - Beyond Adverse Childhood Experiences Advancing evidence and methods to understand the health consequences of childhood adversit - 21/03/2022
A rising tide of research and policy interest in Adverse Childhood Experiences (ACEs, e.g. child maltreatment, parental intimate partner violence or substance misuse) has led to substantial financial investment in services to prevent the health consequences of ACEs. These initiatives rest on estimates of the health burden/costs of ACEs. Yet very little research attempts to interrogate the causality of associations between ACEs and health, despite potential confounding by upstream factors such as poverty and genetics. Robust evidence that ACEs causally affect health would strengthen the rationale for investing in interventions that prevent ACEs or seek to mitigate their adverse effects. Yet if some associations are spurious or over-estimates, this risks: costs of ACEs being overstated, scarce public resources being wrongly diverted away from other upstream determinants of health such as poverty, and perpetuating a stigmatising narrative that those exposed to adversity have uniformly poor health.
In BEYOND-ACES, cutting-edge research using prospective longitudinal and genetic data from 6 international cohorts will generate a step-change in evidence about whether ACEs are causally related to health-related behaviours, physical health, and mental health. We will use robust methodologies: difference in difference (DiD) to avoid time-fixed confounding, marginal structural models (MSM) to avoid time-varying confounding, polygenic scores to evaluate gene-environment correlation, and methods to account for genetic confounding. Underpinning this is a cross-cutting programme of methodological innovation: developing DiD and MSM for use with the composite exposures necessary in ACEs research, and evaluating approaches to interrogate whether the health consequences of ACEs differ according to the timing and duration of exposure. BEYOND-ACES will move beyond the current simplistic narrative about ACEs and health, and yield a step change in the quality of research in this field.
B4026 - Characterising the relationships between alcohol use and mental health from adolescence to young adulthood a longitudinal study - 21/03/2022
It has previously been shown that there is a relationship between age of first intoxication (AFI) and mental health disorders. However, many studies in this area tend to focus on the relationship between the AFI and substance-use disorder, rather than other mental illnesses, or how pre-existing mental disorders predict substance-use in teenagers. Burke et al (1990) found that the hazard rate for developing a substance-use disorder is highest when the AFI is between ages 15 and 19 and found that this risk decreases as the individual ages, which is consistent with other literature. This suggests that teenage years are a vulnerable period for individuals as there is a high potential for the development and maintenance of a substance-use disorder. The impact of pre-existing mental health issues on substance use is demonstrated in a study conducted by Sung et al (2004), which found that girls who struggle with anxiety before the age of 16 have an increased risk of substance-use disorder, and boys with a history of depression in childhood and early adolescence also have an increased risk. Research suggested that substance-use disorders can also be a symptom of mental illnesses, for example, Robins et al (1985) found evidence that implies this disorder is a symptom of antisocial personality disorder. However, there is a lack of investigation into whether the AFI is associated with the onset of psychopathological symptoms.
B4028 - Cord blood and pre-school biomarkers mediating the relationship between maternal obesity and offspring behaviour - 21/03/2022
Maternal obesity is a growing epidemic associated with negative outcomes for both the mother and the infant, including pre-eclampsia, gestational diabetes (GDM), and infants born overweight. Emerging evidence also suggests that pre-pregnancy maternal obesity has a detrimental effect on child neurodevelopment, affecting both cognition and behavioural development. This phenomenon is likely a direct result of a suboptimal environment in the womb. However, obesity is also associated with the activation of the immune system, which may further trigger adverse consequences in the developing fetal brain. A second potential pathway through which maternal obesity may act is through changes in the fetal steroid or hormonal environment. Obese women have increased levels of leptin which have been correlated to higher fetal leptin levels. Leptin is believed to have a role in fetal brain development, specifically behavioural regulation. Though studies have begun examining the role of maternal pre-pregnancy obesity on childhood neurodevelopment, only one study has considered the role of inflammation or hormones as potential biological mechanisms of action. Nevertheless, their role remains unclear.
B4027 - Long term impact of the COVID-19 panemic COVID Q 6 - 21/03/2022
We have deployed 5 questionnaires to date through the COVID-19 pandemic, together with serology testing and tracked a wide variety of issues around physical and mental health and the impact of the pandemic. We continue our work in the National Core Studies (NCS) consortium to examine the impact of the pandemic across a number of cohort studies (10 in total). This questionnaire will be deployed across these studies.
B4004 - INTIMATE PARTNER VIOLENCE PERPETRATORS THE ORIGINS B3087 - 14/03/2022
Intimate Partner Violence (IPV) is defined as any violent behavior within an intimate relationship or any other controlling behavior that is conducted by a current or former partner. It is the most common form of violence in women which constitutes a major public health problem worldwide. The current explanatory theories of IPV perpetration can be summarized as feminist/sociocultural, social learning theory-based intergenerational transmission and psychological/psychosocial. According to the feminist/sociocultural theory, domestic violence is a consequence of “patriarchy”. From this view, violence is used as a form of power and control of women by men. The intergenerational transmission theory asserts that domestic violence is based on the exposure to, or observation of, violence in the family of origin. Psychological theories propose that there are psychological, psychiatric, behavioural and neurological risk factors for domestic violence perpetration. In the study of IPV perpetration, it is important to consider the variables addressed by such theories as a whole and from a developmental perspective and there is no study that simultaneously considers all the variables of these explanatory theories. The general aim of our study is to identify those etiological mechanisms linking risk factors for IPV perpetration across development. This study will be the first one that sheds light on which the origins of IPV perpetration are by knowing how IPV perpetration develops. Implications in terms of prevention and treatment will be of a great relevance for public health.
B3980 - The predictive power of autobiographical memory in shaping mental health of young people - 14/03/2022
The way in which we remember our past - our autobiographical memory - plays a key role in how we think and feel about ourselves and how we imagine our future. As such, dysfunction within the autobiographical memory system can have a lasting impact on mental health. In this study, we are interested in whether the ability to retrieve specific, detailed memories of the personal past for both positive and negative events can influence whether adolescents develop mental health issues in the future. There is lots of previous research which suggests that having trouble recalling specific memories does predict mental illness in the future, and our study is particularly interested in whether factors such as life stress or family history of mental illness may influence this relationship. We are using meta-analysis to compile datasets from young people all around the world to try and answer this question, and to ensure that our results accurately represent all young people.
B4020 - ALSPAC EMPHASIS study of childhood height and DNA methylation - 21/03/2022
The aim of this research is to determine the relationship between DNA methylation at the SOCS3 region and both height and mothers social class. Work leading up to this proposal has indicated that SOCS3 methylation may be associated with height and stunting in cohorts based in Lower Middle Income Countries (LMICs). Analysis in ALSPAC will help to answer whether these associations are also present in High Income Countries (HIC) such as the UK. Analysis of genetic data will determine the variance in DNA methylation determined by genetic and/or environment and the causal direction of any associations identified.
B4015 - Genetic determinants of childhood adversity - 09/03/2022
Experiencing adversity during childhood, such as maltreatment or family dysfunction, is associated with worse physical and mental health. However, it is possible that associations between childhood adversity and subsequent health are confounded by genetics. Recent studies have demonstrated associations between various polygenic scores and adverse experiences including trauma (1) and bullying (2). Understanding this gene-environment correlation is the first step towards deriving the appropriate confounding adjustments to better estimate the causal impact of childhood adversity on later health.
1 - Peel A et al. Genetic and early environmental predictors of adulthood self-reports of trauma. Br J Psychiatry
. 2022 Feb 2;1-8. doi: 10.1192/bjp.2021.207. Online ahead of print.
2 - Schoeler et al. Multi-Polygenic Score Approach to Identifying Individual Vulnerabilities Associated With the Risk of Exposure to Bullying. JAMA Psychiatry
. 2019 Jul 1;76(7):730-738. doi: 10.1001/jamapsychiatry.2019.0310.
B4018 - Understanding adolescent and early adulthood mental health outcomes of intellectual disability - 14/03/2022
Individuals with an intellectual disability (ID) may be more likely to suffer from mental health problems than the general population. We aim to investigate the relationship between ID and mental health using data from a longitudinal study of over 14000 children born in the early 90s with ongoing data collection. We will investigate whether specific risk factors such as cognitive ability, sensory impairments and life events such as bullying may influence this relationship and act as modifiable targets for intervention.
B4007 - Genetic Influences on Sibling Bullying and Mental Health - 09/03/2022
Sibling bullying is highly prevalent. Nearly 50% of children are involved in one form or another, with higher rates in some neurodiverse children. Sibling bullying is associated with poor mental health. What remains unclear is if a) sibling bullying leads to poor mental health or whether children with poor mental health are more likely to experience sibling and b) what the rates of sibling bullying are in children with other types of neurodiversity. We will use a genetically sensitive design to address this gap in knowledge.
B4013 - Asthma Phenotypes and Sputum Biomarkers in High- Medium- and Low-Income Countries - 09/03/2022
Asthma remains a major global public health concern. However, asthma prevalence is different in high-income countries (HICs) and low and middle-income countries (LMICs), and what we know about asthma pathology is generally based on studies in HICs. To address this, the World Asthma Phenotypes Study (WASP) study started in 2016 to better understand types of asthma in five centres around the world; the UK (Bristol: ALSPAC), New Zealand, Brazil, Ecuador, and Uganda. The main objective of this specific project (which is part of WASP) is to focus on the association between soluble airway biomarkers, patterns of airway inflammation, and clinical characteristics, to better understand and characterise types of asthma in the different centres.
B4000 - General disease factor and developmental risk factors - 01/03/2022
More and more evidence suggests a link between mental and physical conditions such as ADHD and obesity (Cortese et al., 2016), eating disorder and inflammatory bowel disease (Larsen et al., 2018). Similar to the g-factor and p-factor (Caspi et al., 2015), Our team at University of Southampton has hypothesised one general disease factor (d-factor; Cortese et a., 2021) that summarises individual’s propensity to both mental and physical disorders, and accounts for the comorbidity between mental and physical conditions. We have been testing this hypothesis using two longitudinal datasets: the millennium cohort study and the 1970 British Cohort Study. We found that from adolescence to adulthood, association between mental and physical conditions strengthen gradually, and that there is indeed a general d-factor that explains individual propensity to develop comorbid mental and physical conditions. We would like to (1) test the hypothesis of d factor longitudinally from childhood to early adulthood, (2) examine the genetic and epi-genetic foundation of the general disease factor, and (3) investigate environmental risk factors related to higher d-factor scores.
B4014 - Depression and smoking on the plausibility of the missing not at random assumption using fast causal algorithms - 01/03/2022
If we want to look at the impact of a given exposure on depression outcomes, we commonly require the assumption that the missingness in our depression indicator is "at random". "At random" is something of a misnomer here, and means "random conditional on measured covariates". In the instance that missingness is in fact not at random, i.e. depression itself affects participants likelihood to respond - then common analytical procedures to investigate the impact of exposures on depression may be biased.
We will develop a method to attempt to address this gap, using the effect of smoking on depression at 18 as a question to demonstrate our proposed approach, which will seek to provide testable conditions under which we can falsify the "missing not at random" assumption.
B4012 - Genome-wide investigation of heritable complex traits in infancy - 09/03/2022
Our recent review of published twin studies revealed that infant behaviour is significantly heritable, with twin heritability estimates ranging between 30 and 80% for psychologically-relevant traits. However, thus far there has been little attempt to study the genetic bases of infant behaviour looking at the DNA.
With this study, we aim to explore the role of common genetic variation on heritable infant behavioural traits. Genome-wide association analyses will be performed for infant psychologically-relevant characteristics collected in the first three years of life in the ALSPAC cohort. Results will then be combined with results from other cohorts in a meta-analysis on a large world-wide sample. Following this gene-discovery phase, we will use state of the art statistical genetic methodology to further investigate genetic influences on infants’ behaviour.
B4011 - Prenatal air pollution fetal growth inflammation and childhood adiposity LongITools and LifeCycle - 28/03/2022
This proposal is part of LongITools (B3289) and LifeCycle projects.
There is inconsistent evidence of an association between prenatal exposure to air pollution and adiposity in childhood. Some studies suggest positive associations, possibly with stronger magnitude in boys, some find no association, and others find inverse associations between prenatal air pollution and adiposity in childhood. Most studies have been relatively small (<3,500 participants) and assess adiposity at a single time point.
The potential mechanisms linking air pollution to adiposity are still uncertain. Maternal exposure to air pollution may affect fetal growth, and intrauterine growth restriction will influence later-life adiposity. Inflammation is another hypothesised mechanism of the association between prenatal air pollution and offspring adiposity, and this might also be part of the fetal growth pathway.
Using data from three birth cohorts (ALSPAC, BiB and Generation R), this project will assess the association of different measures of air pollution (PM10, PM2.5, NO2 and NO) during pregnancy with fetal growth, trajectories of adiposity in childhood, and maternal and offspring inflammation. We will also explore possible sensitive windows by assessing trimester-specific associations, and whether associations differ by sex. If associations of air pollution with fetal growth, inflammation and childhood adiposity are evident, we will explore and quantify possible mediation by fetal growth and inflammation in the association between prenatal air pollution and childhood adiposity.
B3966 - Stratification of ADHD developmental trajectories with evidence from environmental risk factors epi-genetics and neuroimaging - 28/02/2022
Individuals with attention deficit hyperactivity disorder (ADHD) may undergo different developmental trajectories throughout adolescence. Previous evidence has indicated that neural signatures and genetics could help to distinguish individuals with persistent ADHD symptoms from those remitted. However, little evidence has been provided to demonstrate whether environmental risk factors, such as substance use, could also affect the development of ADHD symptoms.
B4008 - Association between air pollution and cardiovascular health in young adults LongITools - 28/03/2022
This proposal is part of LongITools project (B3289).
A growing body of evidence has shown that exposure to air pollution is associated with higher blood pressure/hypertension, cardiovascular events, and cardiovascular mortality. However, few studies have assessed the impact of air pollution on cardiovascular health in younger individuals.
A meta-analysis of cross-sectional and longitudinal studies has shown that an increase in PM2.5 was associated with higher carotid intima-media thickness (CIMT). Even though there is a growing body of evidence on the association between air pollution and cardiovascular outcomes later in life, very little is known in younger individuals [3]. A study carried out with young adults (mean age 28, SD 1.0) showed that nitrogen dioxide (NO2), but not PM2.5, was associated with increased pulse wave velocity (PWV).
It is also possible that the associations between air pollution and cardiovascular health outcomes differ according to intermediate factors, such as body mass index (BMI). A study with 158 individuals aged 17-22 years found that a 1 standard deviation (SD) change in long-term NO2 exposure was associated with 11.3mg/dL higher total cholesterol and 9.4mg/dL higher low-density lipoprotein cholesterol (LDL-C), and these associations were stronger amongst obese participants, suggesting that obesity might exacerbate the effects of air pollution.
The aim of this study is to assess the long-term associations of air pollution with several measures of cardiovascular health in young adults (i.e. central and peripheral blood pressure, heart rate, PWV and CIMT) and explore possible effect modifications by BMI in these associations.
B4009 - Early-life ambient environmental exposures and blood pressure trajectories LongITools - 28/03/2022
This proposal is part of LongITools project (B3289).
Blood pressure tracks from childhood to adulthood, and elevated blood pressure in childhood or adolescence is associated with several intermediate markers of cardiovascular disease (CVD) and with CVD events and mortality in adulthood. There is a growing body of evidence showing that ambient environmental exposures, such as air pollution, noise and many characteristics of the built environment are associated with high blood pressure/hypertension in adulthood, and some associations with blood pressure have also been observed in children.
Early-life, especially prenatal and early postnatal, is a period of rapid development and particularly vulnerable to environmental factors, and adverse exposures in this period could lead to long-term health effects, including higher risk of CVD. Some studies have shown associations between prenatal ambient environmental factors and blood pressure in children, including some measures of the built environment (e.g., facility density, facility richness and building density), noise, temperature, and air pollution. Investigating whether early-life ambient environmental factors are also associated with changes in blood pressure in different developmental periods will further contribute to the understanding of the importance of environmental exposures to the risk of hypertension across the life-course.
Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we aim to assess the association of a range of ambient environmental exposures in early-life with changes in systolic (SBP) and diastolic blood pressure (DBP) during three developmental periods: childhood, adolescence, and early adulthood. We will also seek to replicate the associations found in ALSPAC in other independent European cohorts part of the LongITools project (Generation R, EDEN, PANIC and NFBC 1986).
B4010 - Longitudinal associations of air pollution noise and built environment with glucose and insulin-related traits LongITools - 28/03/2022
This proposal is part of LongITools project (B3289).
Key modifiable risk factors for hyperglycaemia/diabetes include unhealthy diet, lack of physical activity and overweight/obesity. These are, in part, determined by the built environment, which comprises components such as walkability index, accessibility, population density, land use mix, and food environment. Most of the research assessing the association between built environment and glycaemic traits assesses type 2 diabetes mellitus (T2DM) in adulthood as an endpoint. Very few studies have assessed the association between the built environment and glucose and insulin-related traits in children/adolescents.
The association between air pollution and glucose and insulin-related traits has been more widely studied. Exposures to PM10 and PM2.5 have been associated with higher fasting blood glucose, and several meta-analyses have shown that air pollution is associated with the prevalence and incidence of T2DM. Air pollution, more specifically NO2 and PM10, has also been associated with insulin levels and insulin resistance, and some of these associations have been observed in childhood.
There is also evidence for associations between noise and higher prevalence and incidence of T2DM. To the best of our knowledge, no studies have assessed noise and glucose and insulin-related traits in childhood/adolescence.
This study aims to assess the associations of built environment, air pollution and noise with longitudinal changes in glucose, glycated haemoglobin, insulin and insulin resistance from childhood to early adulthood using data from European prospective studies.
B3992 - Personalizing the assessment of pediatric short stature by utilizing common genetic variation in height and developmental timing - 21/02/2022
Growth during childhood can be disrupted by a number of diseases. Because of this, the longitudinal assessment of height is an essential aspect of preventive pediatrics. During these assessments, a child's height is measured and compared to the distribution of heights for that patient's age and sex based on population reference standards. Those children with height measurements that are two standard deviations below the mean are classified as having short stature. As short stature can be an indicator of growth failure due to underlying disease, many children are referred for further specialist care. However, the vast majority (75-99%) do not have disease after specialist evaluation and are instead deemed to have genetic/familial or idiopathic short stature [ISS]. These umbrella terms capture the known entities of familial short stature (FSS) and constitutional delay of growth and puberty (CDGP) as well as children whose short stature remains unexplained. The known entities of FSS and CGDP make up a substantial portion of the “benign” diagnosis of ISS. The traits underlying these conditions—height and pubertal timing—are highly heritable and thus, a significant portion of a patient’s genetic baseline can be quantified with the use of polygenic scores (PS), which measure the cumulative contribution of common genetic variants associated with a trait. We propose that using PSs to adjust the existing reference standards for a child's genetic predisposition to height and puberty pubertal onset will improve the value of growth screening.