Proposal summaries
B4128 - Interplay between genetic risk for metabolic syndrome and mental illness on childhood development outcomes - 15/08/2022
Individuals with a mental health condition are more likely to develop metabolic syndrome, which is a collection of risk factors for heart disease like elevated blood sugar, cholesterol, and blood pressure. Conversely, those with metabolic syndrome are also at higher risk of mental illness. This relationship can be partially explained by factors like lifestyle and medication; however, shared biology also influences the cardiovascular system and brain. For example, there is emerging evidence that there are genetic risk factors that are related to both mental health and cardiovascular disease. The impact of this genetic risk for both disorders remains poorly understood in children and adolescents. Given early intervention is important for both mental illness and heart disease, understanding these relationships may assist to identify how best to implement early intervention. This study will investigate individuals with high genetic risk for both mental health conditions and heart disease to establish whether this impacts their psychological and physical development.
B4129 - Characteristics of Converters to and Deconverters from Traditional Religious Beliefs and Behaviours - 15/08/2022
Our Co-investigator, Ralph Hood, has undertaken studies of individuals who have left their religion and those who have stayed or converted using longitudinal data in two countries – Germany and the USA. ALSPAC provides a valuable data set to investigate whether the factors that predict such events are similar in the UK, and whether the individual that makes such a change benefits psychologically in the longer term.
B4115 - Adverse Childhood Experiences and Violent Offending - 09/08/2022
Our proposed project is primarily centred on the research topic of diversion away from the criminal justice system. Specifically, we will chart the developmental interplay between person-centred clusters of adverse childhood experiences (ACEs) and violent offending (assault and use of a weapon) during adolescence. In doing this we hope to identify which clusters of ACEs are most salient for subsequent violent offending. We will also investigate whether these differ for marginalised groups.
B4123 - Climate change sustainable diets and religion - 09/08/2022
Human activity is having a dramatic impact on our planet's climate, and measures to reduce carbon emissions to limit to extent of this climate change are urgently needed. In this project, using the recently-collected climate change data in ALSPAC we aim to explore the factors associated with climate change beliefs and behaviours, with a specific focus on both behaviours relating to sustainable diets (i.e., reduction of meat and/or dairy consumption) and religious/spiritual beliefs and behaviours (RSBB).
B4122 - AMOUNT An investigation of changes in young peoples substance use - 15/08/2022
Substance use (SU) by young people (YP; YPSU) can lead to short- and long-term harms. Although YPSU has been falling over the past 20 years in the UK, evidence suggests that it is now increasing again among some groups. Studies suggest that these changes may depend on where YP live, how they socialise, the health/social challenges that they face, and the ways in which they access and use substances.
This project is part of a larger study that is working with YP and other experts to understand in what ways and for which groups of YP SU is changing. We are developing and testing new theories to help us understand the most important factors that underpin these increases. Some factors relate to individuals, including mental health or experiences of the care system; others will relate to wider contexts such as communities, policy, and youth culture, including how drug markets have changed, changes in leisure and recreation, or shifts in attitudes towards SU; and others depend on the interactions between all of these.
In this project we will first examine whether there is evidence that YP may be using drugs to help cope with mental health problems. We will then explore whether YP who use alcohol and have mental health problems have worse outcomes if they also use drugs such as cannabis.
B4124 - Utilising Epigenetics as a Platform for Precision Medicine - 15/08/2022
Complex disorders such as psychiatric conditions often arise from varying combinations of genetic and environmental factors. This represents a major problem for drug development, as the cause of the disease is highly variable from person to person, and as such, drug response rates vary significantly. By examining an individual’s unique genetic risk factors, treatment response rates could theoretically be increased by improving subcategorization of individuals and personalising the administration of appropriate medications. Although genetic risk scores have been developed for this purpose, the use of epigenetic information in the form of DNA methylation remains relatively underexplored, despite the fact this epigenetic modification can simultaneously index both genetic and environmental risk factors. In this study, we will examine whether DNA methylation can be used to refine the classification individuals with complex disorders and better match affected individuals to personalised medications. In addition, we will also explore the relationship between epigenetic risk for complex disorders and measures of biochemical and metabolic traits to determine whether the epigenetic component of complex disorders is associated with changes in druggable, blood-based biomarkers.
B4103 - Quantifying the multi-system impact of antenatal maternal wellbeing across generations - 01/08/2022
Maternal antenatal anxiety, depression, and stress increase the risk for socioemotional and behavioral problems in childhood, effects which persist into early adulthood (O’Donnell et. al, 2014; Pearson et. al, 2013; Robinson et. al, 2008). These findings are consistent with the fetal origins of mental health hypothesis, which posits that exposures in utero contribute to individual differences in mental health outcomes across the lifespan (O’Donnell, Meaney, 2017).
While the association between antenatal maternal wellbeing and child development is well-established, much less is known about the multi-generational impact of antenatal maternal wellbeing on child health and development. Existing findings from multigenerational studies focus on birth weight (Lahti-Pulkkinen et. al, 2018; Drake et. al, 2015), and antenatal lead (Sen et. al, 2015) or diethylstilbestrol exposure (Kioumourtzoglou et. al, 2018). Interestingly, mouse models have shown the multi-generational effects of stress or dietary manipulations on molecular characteristics of the offspring across multiple generations (Ward et. al, 2013; Radford et. al, 2014; Jawaid, Roszkowski, Mansuy, 2018).
In this proposal, we examine multi-generational effects of maternal well-being (encompassing mental and physical health) in an index pregnancy across 2 or more generations. Our analysis framework will consider important confounds including maternal and child genetic variation and will examine candidate biological processes for the transmission of risk e.g. variation in DNA methylation.
B4114 - Social determinants of mental health and cognition in adolescence - 01/08/2022
One quarter of the world’s population is affected by a mental or neurological disorder at some point in their life (WHO, 2001), and depression alone is predicted to be the leading burden of disease globally by 2030 (Malhi & Mann, 2018). These disorders typically manifest early in life, with 74% of diagnoses first occurring under the age of 18 years, and 50% before 15 years (Kim-Cohen et al., 2003). Understanding risk and protective factors underlying mental ill-health, and how these might develop over time, is crucial for the creation of effective prevention and intervention.
As children mature into adolescents, they increasingly interact with, and become more sensitive to evaluation and rejection by peers. Increased sensitivity to social rejection during this period has been associated with decreased mental health (Gao et al., 2017), while the opposite has been found for increased social support (van Harmelen et al., 2017). The environment in which these interactions occur is also changing, with adolescents spending an average of 6 hours each day online, the majority of which is spent on social media sites (Anderson & Jiang, 2018). Exploring these effects cross-sectionally, we found that increased social rejection sensitivity and decreased perceived social support were associated with increased negative mood in adolescents (11-24 years; Grunewald, Deng, Wertz & Schweizer, Under review), and now seek to further investigate these effects longitudinally.
B4121 - Mechanisms linking the natriuretic peptide receptor-C gene to elevated blood pressure Genetic epidemiology study - 01/08/2022
Previous research has identified several regions of the human genome associated with high blood pressure. One such region is the NPR3 gene, encoding the natriuretic peptide receptor-C. Whilst genetic variants in this region are associated with high blood pressure, it is not known which variant/s drive the association or whether the effect on blood pressure occurs through altered expression of the NPR3 gene. This study will use existing ALSPAC data to investigate the association between the NPR3 gene and high blood pressure.
B4109 - Childhood adverse events and breastfeeding associations with pregnancy behaviour and infant outcomes - 29/07/2022
Adverse childhood experiences have been associated with unfavorable health behaviours, somatic and psychological complaints in pregnancy. Beyond pregnancy experiences, a large body of research highlights intergenerational effects of maternal history of early trauma on their offspring. Given the growing interest on early adversity consequences during the perinatal phase, we aim to examine the associations between traumatic childhood events and pregnancy health behaviour, psychological symptoms, birth outcomes, sociodemographics and breastfeeding. For this we intend to include mother-infant pairs from the Avon Longitudinal Study of Parents and Children. Adverse childhood events consist of abuse (e.g. emotional, physical and sexual), neglect, (e.g. emotional and physical) and household dysfunction (e.g. parental mental illness, divorce or incarceration). We measure pregnancy health behaviour (e.g. exercise, smoking, alcohol, BMI), psychological symptoms (e.g. anxiety and depressive symptoms), sociodemographics (e.g. education, social class) and breastfeeding (e.g.initiation and duration).
B4118 - Intergenerational gut bacterial strain transfer - 15/09/2022
The gut microbiome is important for human health, supporting nutrition, pathogen defence and immune homeostasis, with more than 200 species inhabiting each human gut. The majority of the hundreds of microbial species (Bacteria, Archaea, Fungi typically) colonizing each human gut were only recently characterized from metagenomic assembled genomes and new taxa are still being discovered. Systematic studies investigating how these diverse microbial ecosystems are transferred between humans and adapt to their hosts are so far large lacking. Describing dispersal strategies and microbial adaptation to the human host will significantly contribute to understanding and manipulating the gut microbiome to re-set the host health.
B4120 - Investigation of impacts of colour blindness on educational and psychological outcomes - 22/08/2022
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.
B4092 - The Relationship Between Identifiable Health Risk Behaviours And the Development of Severe Mental Illness Within A Syndemic Fram - 22/08/2022
We want to find out in what way everyday habits and behaviours actually can change how people with a severe mental illness experience this illness, and, by finding that out, how we can possibly advise people, GPs, and the government in helping people feel better and live a better life they enjoy more in the long term. To do that, we are collecting information on how active a person with one of three specific mental illnesses keeps; how often they spend time outside, like in a garden, park or forest; how well and how much they sleep; whether they smoke or drink alcohol, and if so how much and when or when not; and how resilient they are personally to the bad or sad things that can happen in life, like having to move or losing their job or a loved one dying. We then try to find out how likely for example a highly active person with for example bipolar disorder is to also spend a lot of time outside in a park or garden, and how likely they are to sleep better and more hours during the night, and whether they smoke or drink alcohol (a lot) or not. And then we check whether them being so active changes how bad they feel with regards to their mental illness, and how their mental illness affects them. And we do the same thing for people with schizophrenia and severe depression. The idea behind it is that all these habits and behaviours make another habit or behaviour more or less likely to happen, so a person who is highly active would technically also be less likely to smoke a lot. And smoking a lot makes it very likely that if you have depression, you don't feel very good and experience a lot of negative feelings, more so than a person with depression who doesn't smoke. We'll be working on this for three years, building a blueprint-model on this collection of information, and then test how strong this model is on other datasets. And if we're right and we can find a strong model of influencing behaviours and habits, then we can use this model to help councils and the government give out better information on how to help make people live a healthier and better life for themselves.
B4119 - Genetic environmental and pharmacological determinants of telomere attrition rates - 04/11/2022
The UK Office for National Statistics estimates that in 50 years’ time, there will be an additional 8.6 million people aged 65 years and over. Longer lifespan has clear benefits, but when it is associated with an increased proportion of the population suffering from age-related diseases, it can pose a burden to individual sufferers and to the economy.
Telomeres are ‘DNA tails’ at the end of chromosomes that shorten as we age, in accordance with the number of cell divisions. The rate at which telomeres shorten is also affected by genetic, environmental and pharmacological factors, which is important because premature telomere shortening is hypothesized to predispose to multiple age-related diseases, including coronary artery disease and rheumatoid arthritis. This is because cells with very short telomere lengths are less able to divide, leading to the accumulation of old, damaged or unhealthy cells within a tissue, and subsequently an increased risk of disease. A deeper understanding of which specific factors affect rates of telomere shortening might allow us to identify who is most at risk for premature telomere shortening and what sort of interventions may be effective at preventing age-related diseases.
This project will use the rich phenotype data within ALSPAC to define genetic, environmental and pharmacological factors associated with telomere length and its rate of attrition.
B4113 - Exploring the epigenetic profiles of vapers smokers dual users abstainers and never users in ALSPAC - 20/09/2022
DNA methylation is an epigenetic change that can influence how our genes are expressed. Smoking has been found to influence DNA methylation, and these changes could be responsible for some of the negative health consequences of smoking. In comparison, the epigenetic changes associated with e-cigarette use are not well known. In this project, we will explore how e-cigarette use is associated with DNA methylation.
B4111 - Research methods in human epigenetics - 18/07/2022
This project looks at methods used in research on human epigenetics, particularly around uses of
sociological and psychological data in devising research questions.
All paperwork stored in relevant B number folder
B4107 - Fathers preconception smoking and offspring DNA methylation A population-based two generation study - 18/07/2022
Animal experiments suggest that exposure to toxins such as found in cigarette smoke may impact respiratory health across generations. Studies in humans are however limited. In this study, we ask if gene activity differs in children whose fathers smoked prior to them being conceived. Differences have been observed in participants of the RHINESSA study. Here we ask if similar differences are observed in ALSPAC participants.
B4101 - Sensitive periods for the effects of depression on suicide risk - 18/07/2022
Depression is one of the most important risk factors for suicide. Almost 60% of people who die by suicide experienced depression at some point in their life. Yet, it remains unclear why only certain people with depression eventually become suicidal. Recent evidence suggests there are sensitive periods in development when life experiences, such as depression, can have stronger effects on mental illness. It is also well documented that suicidality results from both life experiences and genetic risk.
However, most studies of genetic risk for suicide, depression, and subsequent suicidal suicidality focus on people measured at a single timepoint. This limitation prevents us from 1) identifying people who are at the highest risk for future suicidal behaviours and 2) developing timely and effective interventions that prevent suicide in people with depression. As such, this project will use longitudinal data from two birth studies to determine when and how genetic risk and experiences of depression during childhood and adolescence influence suicide risk in early adulthood.
First, we will identify the specific ages and patterns of depression during childhood and adolescence that most predispose young adults to suicide. These results will help us build and implement interventions that are positioned at the best possible time to prevent suicide risk among youth affected by depression.
Second, we will determine whether children and adolescents with increased genetic risk for suicide or mental illness are more likely to become suicidal after experiencing depression at specific ages. These findings will improve our ability to identify youth who are at greater risk for suicide and provide insight into the genetic pathways leading to suicide.
Third, we will identify biological mechanisms that explain the link between depression and suicide. We will focus on epigenetic changes, as they are linked to human health and are thought to reflect both life experiences and genetics. Thus, they may represent a biological pathway through which suicide risk can become “molecularly programmed”. Identifying epigenetic changes that link depression to suicide risk will help guide the development of biomarkers that will allow us to identify at-risk youth quickly and effectively.
In sum, this project will highlight key periods and biological targets that can be used to predict and prevent suicidality among childhood and adolescents who experience depression. These will ultimately catalyse better interventions that prevent suicide in young adults.
B4110 - Genetic evidence for the causal relationship between 25OHD and bone fracture a non-linear Mendelian randomization analysis - 18/07/2022
While previous studies have demonstrated no clear effects of vitamin D upon risk of fracture and lowered BMD in the general population, it is clear that vitamin D deficiency causes increased risk of fracture and a reduction in BMD, as is seen in rickets. Further, RCTs of high dose vitamin D have shown a decrease in BMD after administration of vitamin D. This suggests that the effects of vitamin D upon BMD and perhaps fracture are non-linear.
We therefore propose non-linear MR studies of the effect of vitamin D (as measured by 25(OH)D) on BMD and fracture outcomes. Such findings could help to guide future RCTs and provide clinicians with some insights as to the utility of vitamin D administration in different segments of the population.
B4108 - Special collections Eating disorders in Britain 1980-2010 - 13/07/2022
I am interested in the ways in which eating disorders were being discussed (both popularly and amongst academics/practitioners) and researched in the late 20th/early 21st century. I’m especially interested in ALSPAC because of the specific interest in the impact on eating disorders on maternity (a relatively unusual approach at the time.) I am only interested in material on the eating disorder research components of ALSPAC