Proposal summaries
B4294 - The role of childhood personality traits in adult mental health symptoms - 06/04/2023
Previous research has found partial evidence for a role of personality traits in mental health outcomes. However, many of these studies do not examine all of the big 5 personality traits simultaneously, examine mental health generally, or a small number of mental health symptoms. These studies also tend to examine participants cross-sectionally, without examining the way in which personality traits may influence mental health longitudinally, after controlling for confounders. This study aims to overcome the previous patchwork coverage of this topic by combining a range of exposure and outcome variables in a prospective cohort study.
B4296 - Prevalence of mental health need among 0-4 years old in England - 06/04/2023
The National Mental Health Intelligence Network (NMHIN) has been commissioned by NHSE to determine whether an estimate of mental health need for 0–4-year-olds can be produced, with the aim of being able to produce national and local area prevalence estimates for this age group.
This work included an initial feasibility assessment which was advised by an expert reference group (ERG) of experts in the field. The ERG gave a strong steer of using an existing cohort study that assesses the mental health of the children in this age group, considering limited availability of data around the topic which can be generalized at national level.
Currently, we are looking at developing an interim national prevalence that gives an estimate of mental health need among this age group. This will be done by selecting a study sample from ALSPAC, looking at the mental health outcomes of the study group and then applying the prevalence at a national and local level.
B4299 - Understanding the trajectories of adolescent and early adulthood depression outcomes of attention deficit hyperactivity disorder - 06/04/2023
Individuals with Attention deficit hyperactivity disorder (ADHD) may be more likely to suffer from mental health problems than the general population. We aim to investigate the relationship between ADHD and depression 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 bullying and childhood adversity may influence this relationship and act as modifiable targets for intervention.
B4300 - STAGE Stay healthy through ageing - 06/04/2023
The prevalence of multimorbidity increases with age. Therefore, to prevent it and mitigate its impacts, we need to understand how multiple factors at different stages of the life course affect an individual’s health trajectory with ageing.
Currently, an important knowledge gap exists in this area as most research has focused on single life stages and/or single diseases, and often only at adult ages when multimorbidity appears. This overlooks the sequence and dynamic development of comorbidities in the life course.
We will address this gap by creating trajectories of multimorbidity by disease, physiological function and medication usage across all life stages.
B4279 - Investigation of impacts of colour blindness on educational and psychological outcomes v2 - 03/04/2023
X-linked, red-green colour blindness (CVD) is a congenital condition affecting 8% of men (0.4% of women). Depending on type and severity, affected individuals have significant difficulties discriminating a wide range of colours facing wide-ranging challenges on a day-to-day basis (e.g. interpreting colour-coded information at the workplace or recreational environments). A growing impact is expected in educational settings due to an increasing reliance on colour resources in schools. Unfortunately, a study using a birth cohort from 1958 (Cumberland et al, 2004) has reported a lack of impact of colour blindness on Maths and reading ability but fails to account for the increase in colour in classrooms in recent years. Regrettably the publication led to the cessation of CVD school screening in 2009, preventing children from accessing more appropriate resources.
In contrast, a number of authors have argued that CVD can increase difficulties experienced in a range of school subjects including Sciences, Maths, Art, PE and Geography as such subjects may use colour to explain concepts, give instructions and require it in problem solving tasks. Alongside any academic implications, CVD has been found to have an effect on social, psychological and emotional outcomes. For example CVD children may experience teasing from classmates.
We here propose to investigate the potential impacts of CVD on education and emotional outcomes in a more recent cohort.
B4278 - Evaluating the relationship between early life adiposity measures and later life disease susceptibility - 27/03/2023
Analytical approaches which disentangle heterogeneous effects on trait susceptibility provide important insight on the relationship between complex traits and disease. Lifecourse Mendelian randomization (MR) is a novel statistical approach which has been developed to address lifecourse specific effects on disease susceptibility (1, 2, 3). Additionally, stratifying instrumental variables based on tissue derived gene expression data provides further molecular context to interpret the effect (4, 5).
Evaluation of the relationship between lifecourse and tissue dependent effects on biomarkers measured in early life provides important insight on key etiological and susceptibility windows of disease. The results of a recent analysis have provided evidence of a direct effect for the brain-mediated component of body-size on the adipose tissue secreted hormone leptin measured at age 10 in the lifecourse (Richardson et al, in revision). Through the integration of tissue-specific data, this approach highlights the etiological importance of appetite regulation in the links between adiposity and leptin levels in early life.
Additionally, this study also showed evidence for an effect of adult body-size on circulating leptin measured in childhood (when accounting for the effect of early life body size), which is directionally implausible. This raises the possibility that the adult derived exposure may be a strong predictor for traits in early life which have an effect on childhood leptin levels. In this project we will further characterize the relationship between adult body size and early life adiposity measures and a range of childhood biomarkers to refine the interpretation of this causal relationship.
References:
1. Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey Smith G. Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study. BMJ. 2020;369:m1203.
2. Richardson TG, Power GM, Davey Smith G. Adiposity may confound the association between vitamin D and disease risk - a lifecourse Mendelian randomization study. Elife. 2022;11.
3. Sanderson E, Richardson TG, Morris TT, Tilling K, Davey Smith G. Estimation of causal effects of a time-varying exposure at multiple time points through multivariable mendelian randomization. PLoS Genet. 2022;18(7):e1010290.
4. Leyden GM, Shapland CY, Davey Smith G, Sanderson E, Greenwood MP, Murphy D, et al. Harnessing tissue-specific genetic variation to dissect putative causal pathways between body mass index and cardiometabolic phenotypes. Am J Hum Genet. 2022.
5. Leyden GM, Greenwood MP, Gaborieau V, Han Y, Amos CI, Brennan P, et al. Disentangling the aetiological pathways between body mass index and site-specific cancer risk using tissue-partitioned Mendelian randomisation. Br J Cancer. 2022.
B4283 - How are Adverse Childhood Experiences Linked to Depersonalisation Biological Mediators and Psychosocial Risk Factors - 27/03/2023
Depersonalisation disorder (DPD) is a distressing condition that typically emerges in young adulthood, characterised by detachment from one’s body and self, and/or one’s environment. Individuals with DPD retrospectively report adverse childhood experiences (ACEs) and are objectively evidenced to have a dysfunctional biological stress system. However, no research has looked at the biological mechanisms that translate ACEs into DPD later in life. Using self-report and biological data of parent-child dyads from the Avon Longitudinal Study of Parents and Children (ALSPAC), I aim to fulfil this research gap. Within the ALSPAC data, instances of childhood sexual, emotional, and physical abuse, emotional neglect and family dysfunction are reported separately by both parents (during annual assessment of the child’s development), and by the child (later in life), which can be combined, creating a measure of ACEs that doesn’t rely solely on retrospective reports. Stress system dysfunction is measured by cortisol (a stress hormone) level, interleukin-6 and C-reactive protein (measures of inflammation). At ages 12 (N = 6832), 17 (N = 5217) and 24 (N = 4021), symptoms of DPD were assessed. Using statistical modelling, I am examining whether the accumulation and the timing of childhood abuse translates into DPD symptoms, mediated by abnormal cortisol and inflammation levels. Additionally, factors with potential to provide risk for, or resilience against, developing DPD symptoms are also being evaluated to provide a comprehensive representation of how DPD symptoms may develop. These include sleep, drug use, attachment, maladaptive cognitions and social position.
B4286 - The role of prenatal alcohol exposure in predicting criminality A cohort study - 27/03/2023
Studies conducted using animals have been instrumental in describing the brain impairment and physiological processes that cause prenatal alcohol exposure (PAE). Research has shown that similar brain and physiological features are likely to be affected in those displaying
increase criminality and behavioral disorders. Some features affected include inattention, impulsivity, the poor executive functioning, impulse control, memory and cause and effect thinking.
Fetal alcohol spectrum disorder (FASD) is attributed to the effects of PAE, and has been associated with a two to six fold increase in mental disorder diagnosis in offsprings of alcohol binge drinking mothers. Youths with FASD are 19 times more likely to end up incarcerated than those without. Cigarette smoking and illicit drugs used in pregnancy also contribute to adverse pregnancy outcomes and are important risk factors of criminality.
Offspring of mothers who drank during pregnancy especially heavy drinking of greater than 21 units a week, will be at an increased risk for adolescents antisocial activities and conversely criminal activities in adulthood. It is also likely that there is a positive relationship between the quantity of alcohol used and number and intensity of antisocial activities and criminal activities.
B4261 - Genomics metabolomics and inflammatory markers and Eating Disorders and related behaviours across the life span and generations - 27/03/2023
Eating Disorders (ED) (full and partial syndrome anorexia nervosa and bulimia nervosa and binge eating disorder) are life- threatening illnesses that start in adolescence and affect between one and two in ten adolescents and young adults. There is a lack in our understanding of why eating disorders develop, which affects our ability to develop treatment and adequately prevent eating disorders. This project builds on our previous studies in ALSPAC, showing that metabolism and growth might play a role in the development of eating disorders. We aim to combine metabolic function, body composition, blood and inflammatory markers, as well as genetic information to understand progression and development of eating disorders and related symptoms in the 3 generations of ALSPAC participants. This study will be fundamental in understanding how eating disorders develop and progress across the life span.
B4288 - Rethinking Special Educational Needs - 27/03/2023
In the United Kingdom, 10-15% of school-aged children have a special educational need (SEN). Children with SENs have impairments in language, learning, cognition, and social functioning. The diagnostic criteria for SENs are not, however, always fit for purpose. At-risk children can be missed or mislabelled meaning that they go without the support they need. This is compounded by the fact that SENs often co-occur with mental health difficulties but diagnostically they are usually considered separate. Therefore, a fundamental rethink of how children’s SENs and mental health difficulties are conceptualised is needed.
We will use data from two large UK-based datasets to 1) investigate the inter-relations between, and clustering of, SENs and mental health difficulties. Rather than looking at diagnoses, we will focus on how underlying strengths and difficulties in language, learning, cognition, social functioning, and mental health co-occur. In doing this, we will identify skills dimensions that map directly on to children’s needs, regardless of diagnostic label. Next, 2) we will investigate how these dimensions of skills cluster in children and how they compare with existing diagnostic labels in predicting children’s outcomes.
Finally, 3) we will identify environmental pathways through which risk is transmitted whilst controlling for genetic confounding. This will determine who and which environments should be the targets for early intervention to mitigate genetic risk for SENs and mental health difficulties.The proposed project will, therefore, mark a fundamental shift in how SENs and mental health difficulties are conceptualised, identified, and how at-risk children are supported.
B4290 - Whole Exome Sequencing - Completing Coverage for all ALSPAC participants - 05/04/2023
Whole exome sequencing (WES) is a method used to generate the sequence of all protein encoding regions of the human genome. ALSPAC has already obtained WES data from all available DNA from G1 participants (original children) and a subset of G0 parents. ALSPAC has been included in an MRC funded initiative to complete WES sequencing in some cohort studies. This will fund generating WES on approximately 11,000 samples from the remaining G0 parents and G2 (CoCo90s). This, together with existing data, will ensure WES is available from all suitable ALSPAC DNA samples.
B4289 - Mediators of the relationship between maternal religious belief and offspring mental health - 20/03/2023
This project is intended to build upon several previous studies that examined the relationship between maternal religious belief and offspring mental health. This time we want to explore mechanisms that help to explain this relationship. For example religious belief may influence social support, or parenting style, which may then influence offspring mental health.
B4280 - Olink Inflammation Panel and Cardiovascular Phenotypes - 20/03/2023
Systemic inflammation is associated with increased risk in the development of atherosclerosis as well as other cardiovascular diseases (CVD). Recent trials have thus investigated whether immunotherapies may decrease the risk of CVD (Ridker et al. 2017; Tardif et al. 2019; Liberale et al. 2021). However, there remains a dearth of knowledge regarding which inflammatory proteins may play an aetiological and/or mediating role, and thereby may be potential therapeutic targets in the prevention of CVD. We seek to investigate the associations of the 92 Olink inflammatory proteins, measured in approximately 3000 mothers, 3000 children at age 9 and another 3000 children at age 24, with changes in carotid intima-media thickness (cIMT), pulse wave velocity (PWV) and blood pressures. We will also perform the analyses on the inflammatory biomarkers Glyoprotein Acetyls (GlycA) and C-reactive protein (CRP), as well as IL-6 measured in the 9-year-olds via clinical chemistry, since IL-6 is the only protein measured by Olink that has been measured previously in ALSPAC to be used as a validation.
B4285 - Study of how adiposity in pregnancy has an effect on outcome SHAPES an Individual Participant Data IPD meta-analysis - 20/03/2023
Current guidelines use body mass index (BMI) to predict which women have increased risk of developing pregnancy complications and require additional care. BMI is an inaccurate measure to predict risk and leads to many women receiving inappropriate care, makes health outcomes worse and wastes NHS resources. Being overweight (BMI between 25 and 29) or obese (BMI 30 or above) is associated with pregnancy complications including diabetes, preterm birth, and death of mother or baby. Guidelines recommend that obese women receive costly high-risk care including additional referrals, tests and closer monitoring. This is unnecessary for half of obese women who don’t develop pregnancy complications, approximately 87,000 women/year in England. Almost half of overweight women do develop complications, approximately 103,000 women/year. Using obese BMI in guidelines wastes resources and increases anxiety for obese women inaccurately labelled as high-risk, and overlooks many overweight women who do require additional care. BMI does not assess where body fat is stored. When fat is stored in the upper-body there is an increased risk of developing certain diseases. Someone with a “healthy” BMI who stores fat around their waist can have a higher risk than someone with obesity who stores fat on their hips. Alternative measures can identify where body fat is stored (e.g. waist size, ultrasound examination). These are called adiposity measures. This research will look at whether adiposity measures can predict which women will develop complications in pregnancy to help the NHS target care to women who really need it.
B4287 - Gene-by-environment genome-wide association study GWAS of lipid traits influenced by alcohol consumption in - 13/03/2023
The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium invites ALSPAC and Bristol researchers’ to take part in a large GWAS of lipid traits (incl. high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides). The main aims of CHARGE’s GWAS are to (1) identify novel loci for lipids trait separately by sex; (2) identify gene-alcohol consumption interaction effects on lipid traits separately by sex. These analyses will follow the ‘Phase II Analysis Plan for Alcohol and Lipids’ version 2.0 provided by CHARGE. Only GWAS summary statistics will be shared with CHARGE. Based on the GWAS results, subsequent analyses (e.g. validation of the gene-by-environment effects using longitudinal data of lipid traits, and Mendelian randomization) would be suggested by CHARGE.
B4282 - Maternal and foetal genetic determinants of circulating GDF15 and nausea and vomiting in pregnancy - 04/07/2023
We have shown that spelling mistakes in a woman's genome can make her more likely to develop severe nausea and vomiting in pregnancy (also known as 'morning sickness') likely by altering the sensitivity to a hormone called GDF15. This hormone circulates in the blood and is well known to act on the brain known to to induce nausea and vomiting. GDF15 is made by the placenta in large amounts, and increases markedly in pregnancy, however, we do not understand how changes in the unborn baby's genes affect how much GDF15 the placenta makes or how this might alter the risk of nausea and vomiting in pregnancy.
B4276 - Exploring the relationship between health and loneliness - 13/03/2023
Previous studies have demonstrated that loneliness is related to poorer health outcomes across a range of health conditions and traits. However, it is unclear whether these represent causal relationships i.e., increased loneliness leads to poorer health outcomes and what the direction of effect is if so. In addition, further investigation is needed to examine the extent of the impact of loneliness across a range of physical and mental health outcomes. In this project we will examine this further.
B4248 - Genome-wide association study of inflammatory proteins in ALSPAC Mothers and offspring - 07/03/2023
The rationale for this project is to identify protein quantitative trait loci (pQTLs), which are robust connections between a gene variant and the levels of a protein, across the life course. We will conduct genome-wide association studies (GWAS’s) of protein levels at three separate timepoints and compare pQTLs at these different timepoints. Associations with independent lead variants within 300 kb window of the gene boundaries of the protein-coding gene are defined as cis-signals, and otherwise in trans. In this project, we will estimate the proportion of pQTLs that are in cis versus in trans at each of the three timepoints. We will investigate how much of the longitudinal correlation in inflammation levels is explained by genotype. We will also evaluate the relationship of pQTL with other down-stream phenotypes, including traits and diseases, and quantify the contribution made by pQTL to genetic variance in several common complex diseases that have previously been the subject of genome-wide association studies (GWAS).
This project will use the ALSPAC proteomic data, which consists of 92 proteins measured by Olink, measured in approximately 3000 mothers, 3000 children at age 9 and another 3000 children at age 24. We will also perform the analyses on the inflammatory biomarkers Glyoprotein Acetyls (GlycA) and C-reactive protein (CRP), as well as IL-6 measured in the 9-year-olds via clinical chemistry, since IL-6 is the only protein measured by Olink that has been measured previously in ALSPAC to be used as a validation.
B4275 - Agreement between official records and self-reports of crime A cross-national comparison - 27/03/2023
Do official records and self-reports of offending identify the same individuals? And does this depend on the context and/or individual characteristics? These are critical questions at the heart of crime and violence research. Official records and self-reports represent the two primary methods for measuring offending. However, official records only capture the “tip of the iceberg” as not all crimes are reported to the police. Additionally, there is bias in which individuals and which offences are decided to be recorded as criminal incidents by the police, and there are examples of misidentification errors. On the other hand, self-reports of offending via confidential questionnaires or interviews can introduce different biases, including social desirability (e.g., response falsification), recall error, and selection bias – as individuals who have engaged in criminal activity are less likely to respond to research surveys and interviews.
Few studies have compared the two measures of offending, with most of these coming from the US. While this evidence suggests that both measures are generally concordant, self-reports identify higher rates of criminal offending and a significant proportion of individuals with criminal records fail to self-report. The strength of agreement between official records and self-report has been found to vary by crime types and sociodemographic groups. Cultural context may also represent an important factor influencing the agreement between official records and self-reports given known discrepancies in the prevalence of crime and violence in low- and middle-income countries (LMIC) compared to high-income countries (HIC). However, due to a lack of studies with both official records and self-reports of crime from countries outside of the US, the role of national context is poorly understood.
B4267 - The importance of family relationships over time for childrens adjustment - 06/03/2023
Family environments including relationships between parents and children are crucial for psychological adjustment and mental-health across childhood and adolescence. Parent reports as well as parent and child behaviours during their interpersonal interactions ("transactional" dynamics) are seen as particularly important. Moreover, the onset of mental health problems can disrupt previously healthy parent-child transactional dynamics. The aim of this project, which is an extension of the existing project B2159, is to explore family relationships (siblings and parents) from early to late development and their importance for children's adjustment.