Proposal summaries
B4044 - Maternal employment and childcare associated with socio-emotional health in children - 20/04/2022
Socio-emotional outcomes such as internalizing and externalizing behaviours, and ADHD in young children are associated with subsequent adverse outcomes in adolescence and adulthood such as poor school performance, depression, and antisocial behaviours. Growing empirical evidence suggests that many factors within the home environment are associated with the onset of these outcomes in children. One of these factors is maternal employment status, which for many families serves a critical purpose through increasing financial resources of the family, enhancing women’s careers and independence, and encouraging a more-equal gender role within the family. Nevertheless, some literature has raised concerns regarding the effect of maternal employment on children’s socio-emotional health, although the findings are inconsistent. For instance, some studies found that maternal employment within the first year of childbirth is associated with development of externalizing and internalizing behaviours in children. A few studies found no association, while in some others maternal employment led to improved socio-emotional health especially among minority and low-income populations.The discrepancies in findings can be due to differences in study design, exposure and outcome measurements, and the contextual characteristics of settings. In particular, maternity leave and childcare policies likely play crucial moderating roles in the association between maternal employment and child outcomes.There is evidence that the type, initiation (with earlier initiation due to shorter maternity leave) and quality of childcare impact child development. However, data on the potential additive effect of maternal employment and childcare on children’s socio-emotional health outcomes are scarce. Therefore, to better understand the role of maternal employment and childcare on children’s socio-emotional health and to inform public health policies and interventions related to maternity leave and childcare, new research examining the effect of these factors on children’s socio-emotional health is warranted.
B4035 - Genetic basis of DNA methylation - 13/04/2022
DNA methylation (DNAm) plays a central role in gene regulation. It helps to define how cells respond to environmental signals and, ultimately, contributes to health or susceptibility to disease. DNAm variation is influenced by genetic, molecular and environmental and other factors. However, the amount and the effects of differences in DNAm from one person to another is poorly understood.
A powerful avenue into researching the functional consequences of changes in DNAm levels is to correlate DNA sequence variants such as single nucleotide polymorphism (SNPs) to DNAm levels to find both local and distal (for example on other chromosomes) effects. Having completed the largest genetic study of DNAm worldwide to date (through the Genetics of DNA Methylation Consortium) by scanning 10 million SNPs genomewide, we have identified 270k SNP-DNAm associations. This was achieved by analysing about 400,000 DNAm sites in blood, which is only 2% of 28 million DNAm sites across the genome. There is a huge potential for improved understanding of DNAm variation between individuals and its influence on health and disease by studying other regulatory regions of the genome using EPIC arrays and by comparing different ethnicities. We propose to systematically map genetic influences on DNAm and to compare these genetic influences across ancestries.
B4031 - Measuring the glycocalix - 13/04/2022
ALSPAC is measuring the glycocalyx using Glycocheck. This project aims to look at the correlations of existing data with age, sex and known determinants of cardiovascular disease, to support and inform future grant applications for funding for further collection.
B4039 - Multi domain understanding of observed parent-infant interactions at home - 13/04/2022
Variations in mother–infant interactions have a substantial impact on offspring health and functioning in later life. The accepted gold standard for measuring mother–child interactions is to film interaction between mother and child in lab or home setting from the third person. There are several limitations to this approach, including demand characteristics, increased burden on participants and researchers and a less accurate perception of the infant and mothers actual experience in interaction due to using the third person perspective and often only short snippets of time. The recent advent of head-mounted cameras which can be used in naturalistic home settings addresses these limitations. In addition the team have developed a micro-coding system to allow an assessment of moment by moment interaction behaviours, coded using both micro and automated codes.
Research has shown that use of the headcams detects more maternal behaviours in interaction that are social. The videos from home interactions can be coded, they have so far been analysed using an in-depth micro-coded system. What is not yet known is how the micro-coded interaction behaviours map on to global constructs such as parental “sensitivity” and more specific dyadic processes such as attunement, contingency, coordination, matching, mirroring, reparation, and synchrony (Provenci, di Minico, Giusti, Guida & Muller, 2018). The first stage of this project will involve coding and processing data and conducting analyses to identify behavioural manifestations of these and other parent-interaction constructs.
We will validate the micro-coding and automated coding against global coding of sensitivity using videos from both ALSPAC mothers and fathers. This will allow the identification of the behavioural manifestations of sensitivity using both mother infant moment by moment behaviours, importantly across behavioural domains (i.e, mirroring of facial expressions as well as vocalisations or across behaviours where the affect tone is matched in face in mum and vocal in baby), and with quantification of duration of behaviours and time between behaviours. We will also develop processes to automate, such as face reader outputs, currently being validated in parents , but we need more input to use for infants. Establishing which micro-codes and combinations of behaviour are associated with global parent-infant constructs in mothers and fathers will produce a less labour-intensive method to assess parent-infant interaction. Further, this work has important implications for intervention to enhance parent-infant interaction by identifying specific concrete behaviours to target.
The second stage involves examining associations between the identified parent-infant interaction processes and parental mental health and language and with child cognitive, emotional and behavioural outcomes. We combine a number of researchers with specialism around parent-infant interaction, language development, proximity and body-position, joint attention and emotional and behavioural problems.
B4050 - UK LLC The mental health and wellbeing consequences of contracting COVID19 - 14/04/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4025 - Associations between religion and life events - 11/04/2022
Religion can often be recognized as a source of reassurance for those undergoing major or traumatic events in their lives, providing the understanding that these events have their place within the order of the larger universe (Berger, 2011). Hence the Marxist dictum of religion being the “opium of the people.” However, there is relatively little research done on the inversion of this dynamic, specific types of trauma can also have an impact an individual’s strength of faith (Leo et al., 2021). This is particularly prevalent with death related trauma, often witnessing death of a loved one or colleague could influence individuals to either further embrace their faith or weaken it (Fontana and Rosenheck, 2004; Morris Trainor et al., 2019). This is consistent with the shattered assumptions model that posits that those that have undergone trauma often change their world view to ‘accommodate’ their negative life events (Janoff-Bulman, 2002).
The relationship between traumatic life events and religion has been studied in detail by the scientific community, however, the nature and direction of the relationship is still a contentious topic. A review by Chen and Koenig in 2006 found that of the 11 papers in the review, one found no association, four found a positive association, three found mixed associations, and three found an inverse association (Chen and Koenig, 2006).
In these studies, we aim to investigate the relationship between RSBB and traumatic life events in both directions. To find how participants’ religious beliefs impact how they deal with trauma but also if different life events are associated with a change in one’s religiosity.
Berger, P.L. (2011) The sacred canopy: elements of a sociological theory of religion. Available at: http://www.myilibrary.com?id=591409 (Accessed: 9 March 2022).
Chen, Y.Y. and Koenig, H.G. (2006) ‘Traumatic Stress and Religion: Is there a Relationship? A Review of Empirical Findings’, Journal of Religion and Health, 45(3), pp. 371–381. doi:10.1007/s10943-006-9040-y.
Fontana, A. and Rosenheck, R. (2004) ‘Trauma, Change in Strength of Religious Faith, and Mental Health Service Use Among Veterans Treated for PTSD’, Journal of Nervous & Mental Disease, 192(9), pp. 579–584. doi:10.1097/01.nmd.0000138224.17375.55.
Janoff-Bulman, R. (2002) Shattered Assumptions. Available at: https://www.vlebooks.com/vleweb/product/openreader?id=none&isbn=97814516... (Accessed: 17 March 2022).
Leo, D. et al. (2021) ‘The Effect of Trauma on Religious Beliefs: A Structured Literature Review and Meta-Analysis’, Trauma, Violence, & Abuse, 22(1), pp. 161–175. doi:10.1177/1524838019834076.
Morris Trainor, Z. et al. (2019) ‘Death salience moderates the effect of trauma on religiosity.’, Psychological Trauma: Theory, Research, Practice, and Policy, 11(6), pp. 639–646. doi:10.1037/tra0000430.
B4043 - Examining predictors of COVID-19 vaccine intentions and behaviours in the ALSPAC study - 26/04/2022
It is important to identify the people who may not want to take up the COVID-19 vaccine. For a vaccine to work well 70-80% of the population need to have had it. We will look at factors that might be associated with people who do not want to have the vaccine and also look at the people who have had to see if there is any difference.
B4029 - A summary of pain and related items in ALSPAC - 04/04/2022
This project is part of the Consortium to Research Individual, Interpersonal and Social Influences in Pain (CRIISP), which aims to determine the psychosocial mechanisms underpinning chronic pain. This work will be undertaken across four large cohorts studies, including ALSPAC. In order to identify mechanisms and synthesise data across these cohorts, it is first necessary to identify the measures of pain included within each study. As an extension to the original proposal (B3598), we propose to write a data note to summarise all pain related items in ALSPAC across G0 and G1.
B4032 - Exploring risk pathways between early life adversity and eating disorder symptoms - 04/04/2022
Eating disorders are severe psychiatric conditions that often start in adolescence. They present with other serious health problems, have a high mortality rate, and are becoming increasingly prevalent in the UK population. Prevention of eating disorders is the ultimate aim but knowledge of risk factors for eating disorders is limited.
There is no consensus about the relationship between socioeconomic status (SES) and eating disorder incidence in adolescence as current research is based on cross-sectional studies in adults. Different aspects of SES might have different effects on eating disorder symptoms (e.g., parental education and income). SES might have indirect effects on eating disorders via food insecurity, poor dietary patterns, and early mental health problem, however these hypotheses have not been previously tested.
Our proposed research will help identify childhood risk factors for eating disorders and inform future preventative interventions.
B4042 - DPUK Effect of life course stressors and cognitive status on mental health outcomes during the Covid-19 pandemic - 07/04/2022
Information can be obtained from ALSPAC (B number folder) or DPUK on request
B4033 - The study of rare variants and their longitudinal effects on metabolic and anthropometric traits 28-02-2022 - 100918 - 11/04/2022
We know that some people carry rare mutations that disrupt the normal function of critical metabolic pathways, leading to conditions such as obesity and/or diabetes. Genome sequencing studies are increasingly identifying such rare mutations. Using knowledge about the precise structure and function of the proteins encoded by these genes, as well as experimental data generated in the lab, we can determine which rare variants are likely to be disruptive.
After identifying mutations that disrupt protein function, we can use the wealth of data available in ALSPAC to determine how possessing a disrupted protein affects a persons growth and metabolism. This will allows us to infer the function of proteins in human physiology, and will identify new drug targets for metabolic diseases like obesity and diabetes.
B3853 - Is exposure to toxic metals impacting the health of children and young adults in England - 14/04/2022
Pollutants such as lead, cadmium and arsenic potentially pose a threat to our health, even at low levels of exposure. Exposure before birth and in childhood may have particularly important damaging effects on the developing lungs, brain and cardiovascular system. In this project we plan to measure these pollutants in maternal urine samples taken during pregnancy and in blood samples from the offspring in childhood to see whether levels are higher in mothers and children who are less well off, and whether higher exposure before birth and/or in childhood is associated with poorer lung function, higher blood pressure, and lower IQ and educational attainment in childhood. If these pollutants are affecting children's health, they might be contributing to the poorer health seen in less well off children.
B4037 - UK LLC Comparing the burden of long COVID in the community as measured by self-report and electronic health records - 01/04/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4036 - UK LLC Are immune-mediated diseases risk factors for long COVID - 01/04/2022
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
B4023 - Exploring the impact of early adversity on the development of the immune system - 25/05/2022
Early adversity predicts greater disease risk later in life across numerous outcomes; however, biological pathways are incompletely understood. Previous studies have implicated altered immune function in these relationships, specifically chronic inflammation, which is associated with both adversity and multiple health outcomes, including cardiovascular disease (CVD) and all-cause mortality. While these studies have been informative, inflammation is only one component of the immune system, and there is suggestive evidence that adversity might have broader effects besides heightened inflammation that impact later life health. The immune system consists of two subsystems, non-specific innate immunity and specific acquired immunity. Chronic inflammation represents up-regulation of innate immunity, while studies linking adversity to acquired immunity tend to report suppressive effects. Research in evolutionary biology and ecological immunity has suggested that an up-regulation of innate immunity and down-regulation of acquired immunity could be an adaptive “future-discounting” strategy in harsh and unpredictable environments, as innate immune activation can provide short term benefits but comes with long-term costs to health and longevity, while acquired immunity provides less immediate benefits but enhances future defense.
Consistent with the above model, we have recently found evidence that early adversity (e.g., low SES) in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) predicts a lower percentage of circulating acquired immune cells and higher percentage of innate inflammatory cells in young adulthood. Here we propose to expand on this work by testing whether similar associations are found in the ALSPAC cohort, using immune cell composition data derived from both flow cytometry and DNA methylation (DNAm) at multiple ages.
B4030 - Does religiosity promote cooperative behaviour - 24/03/2022
This project aims to explore whether religion may plausibly cause an increase in cooperative behaviour. Several studies have found an association between religiosity and increased cooperativeness, but few studies have used large-scale longitudinal population-based studies with detailed information on potential confounders to explore this question or assess whether this may be a causal effect.
B4016 - Characterising the relationship between disordered eating behaviours and problematic alcohol use from adolescence to young adult - 21/03/2022
People who exhibit disordered eating behaviours, such as binge eating, restricting, and purging, are at increased risk of problematic alcohol use. It is commonly proposed that this is a partially causal relationship, with behaviours such as binging and restricting actively contributing to the development of problematic alcohol use. This may be because disordered eating behaviours can increase negative affect, reward sensitivity, and impulsivity, which are factors known to contribute to problematic alcohol use.
However, there are also reasons to believe that problematic alcohol use may in turn contribute to the development and maintenance of disordered eating behaviours, through similar mechanisms operating in the opposite direction. Additionally, ‘out of control’ or ‘binge-type’ alcohol use may be particularly distressing for individuals with disordered eating, due to the caloric nature of alcohol, and thus may result in increased compensatory behaviours (i.e., disordered eating behaviours). Longitudinal studies thus far have reported mixed findings regarding the causal direction between disordered eating behaviours and problematic alcohol use and have been hampered either by small sample sizes or poor measures.
Thus, this project aims to investigate and describe the direction(s) of causation between disordered eating behaviours and problematic alcohol use using robust measures and a large sample size.
Furthermore, the literature is unclear on whether purging or bingeing is more related to problematic alcohol use, as many studies have either looked at one or the other, or collapsed them into one category (i.e., ‘bulimic symptoms’). Thus, this study will look to consider the relative magnitude of association of each of these two behaviours, as well as restrictive eating behaviours, and problematic alcohol use.
B4019 - Meta-analysis of Copy Number Variation in Large Consortia - 21/03/2022
[Written by Dr Joseph Glessner]
In the analysis of genetic variation, individual-level data is of great value. Research sites generating such data on human subjects are typically mandated by their institutional review boards (IRBs) not to share this information between institutions and other entities. However, the ability to combine large genetic datasets across research sites is an important tool in understanding the genomic architecture of common complex diseases. Indeed, methods to combine different genome-wide analysis studies (GWAS) of single nucleotide polymorphism (SNP) markers are well established, and they have proved extremely powerful for delving deeper into common diseases such as type 2 diabetes and childhood obesity. However, similar trans-institutional approaches for analyses of copy number variants (CNVs) are relatively in their infancy. Some of the main reasons for this discrepancy include:
1) Non-standard and variable methods to infer CNVs from genotyping data
2) A lack of robust methods for imputation of CNVs across genotyping chipsets
3) The accounting complexities of CNVs across subjects having variable boundaries
This research plan seeks to establish a genome-wide approach to meta-analyze CNVs across sites that comprise the Early Growth Genetic (EGG) Consortium.
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.