Proposal summaries
B4648 - Inference of trait Tail Genetic ArchitectureS - 26/07/2024
Understanding genetic architecture in quantitative traits and complex diseases has been pivotal in biomedical research. Over years of effort and technological advancements, GWASs and sequencing studies have revealed that the genetic architecture of complex traits often comprise of a range of genetic components, including common variant, rare inherited and de novo variants. However, there remains an understudied aspect: the genetic architecture at individuals-level. For instance, individuals in the tails of trait distribution can be predominantly driven by common polygenic variants or by rare/ de novo variants with substantial effects.
B4664 - Search of genetic variants related with lung function a GWAS meta-analysis - 26/07/2024
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. Recently, over a thousand variants in over 500 genes were associated with lung function. Those variants were involved in different cell functions, providing information that brings us closer to understanding the mechanisms underlying lung function and COPD.
In this study, we will investigate a more comprehensive number of variants in genes, using the TOPMed reference panel, given its diverse sample population from both Europeans and non-Europeans, with a total of 97,256 high-coverage genomes, to help identifying variants responsible for lung function impairment.
B4663 - Development of Picky eating and Avoidant restrictive food intake disorder predictors correlates and longitudinal outcomes - 25/07/2024
Picky eating is a common behaviour in children, that can range from being a normal phase in child development to a severe problem that causes negative physical and psychological consequences for the child and greatly impacts families. In its extreme picky eating can be part of Avoidant restrictive food intake disorder (ARFID); a debilitating feeding and eating disorder characterized by avoidant/restrictive eating by volume and/or variety resulting in important physical, health, and social consequences. As ARFID is a relatively new diagnosis, little is known about its longitudinal course and outcomes. Very little research is available on manifestations of ARFID in the general population.
B4659 - Genomics of obesity and overeating and their personality correlates - 19/07/2024
Obesity is the consequence of sustained positive energy balance over time where excess energy intake is the main pathway leading to obesity. Eating behaviors play a significant role in regulating food intake. Commonly used questionnaires measuring eating behaviors exhibit high correlations with each other and have been shown to share an underlying factor varying in severity - uncontrolled eating. Uncontrolled eating is associated with obesity and BMI cross-sectionally and longitudinally. Behavioral genetic models provide evidence that uncontrolled eating is a heritable trait with heritability estimates comparable to those seen in other personality or behavioral traits. Heritable variances of BMI and uncontrolled eating constructs show significant overlap. The genetic overlap between uncontrolled eating and BMI suggests that self-control of food intake may serve as the key mediating mechanism through which genetic factors influence differences in body weight. However, causality in this relationship is not necessarily unidirectional, as higher BMI could also lead to increased levels of uncontrolled eating. Another common construct in eating behaviour is food restriction, or restraint. Together with uncontrolled eating, they explain vast majority of variance in eating behaviour traits. The aim of this study is to investigate the genetic basis of uncontrolled eating and restrictive eating, examine their genetic correlations with various other phenotypes, and assess the causal relationship between uncontrolled eating, restraint and BMI.
B4657 - Investigating the links between bullying and youth violence - 26/07/2024
Successful violence interventions depend on the identification of upstream risk factors, an understanding of their relative importance, and how they relate to each other. The project outlined in this proposal would focus on examining bullying as a potential risk factor. Bullying is a common, worldwide social problem, which tends to peak in early to mid-adolescence as children develop greater independence, form new peer groups, shape their adult identities and behavioural patterns. There can be an overlap between bullying and being bullied – ‘bully-victims’ are those who bully others and who are bullied themselves. The pathway from bullying behaviours in childhood and early adolescence to violent behaviour in young adulthood could be causal, or could reflect common factors that predispose young people to both being a bully or a victim and to later violence, such as abuse, negative peer group influences, low connectedness to school, and poor academic achievement.
B4654 - Height-GaP a quantitative index of human growth conditions deployable at any age - 12/07/2024
Adverse exposures and events during the period of early-life growth are increasingly recognized as important to later-life disease risk. For example, up to 50% of chronic obstructive pulmonary disease (COPD) has been linked to impaired lung growth early in life. A challenge to understanding and exploiting this knowledge is the lack of a simple method to quantify the cumulative impact of adverse early-life growth conditions among adults. This amendment proposes to validate a novel quantitative index of early-life growth conditions that can be deployed across the lifespan.
A recent genome-wide association study of 5.4M adults reported a saturated map of genetic variants associated with height that accounts for over 90% of trait heritability and explains up to 45% of trait variance.5 Since human height is determined in part by genetics and in part by early-life growth conditions, it follows that the difference between measured height and genotype-predicted height (height-GaP) may represent a quantitative and cumulative index of adverse early-life growth conditions. In support of this hypothesis, analysis of UKBiobank data demonstrated that a larger height-GaP deficit was associated with several retrospectively ascertained early-life factors known to adversely affect growth, as well as subsequent all-cause and respiratory mortality.
Retrospective assessment of early-life growth conditions limit the strength of inferences that can made from these UKBiobank observations and motivate this amendment to our current ALSPAC proposal, which is already examining a genotype-based index and lung function.
B4653 - Integrating social science and genetics to better understand transmission of social inequality - 16/07/2024
Social inequalities exist across a range of social and health outcomes.3,4 They are harmful to individuals and have been exacerbated by the Covid-19 pandemic and cost-of-living crisis.5,6 The UK is one of the most unequal developed nations,7 where inequalities cost an estimated £106bn a year8 and are a largely agreed national policy priority (e.g., All Our Health; Levelling Up). Previous research has largely focussed on social or genetic influences in isolation, ignoring one of two truths; that population level social and cultural factors impacts individual outcomes, and that biology has an impact on human behaviour. This project will address the urgent issue of social inequality by examining how (dis)advantage is transmitted from parents to children. It will draw on methods from population genetics to improve evidence and complement existing social scientific research into the formation of inequalities.
B4644 - Risk perception of extreme weather and tick-borne disease in cities - 04/07/2024
This is part of a work package in the team's UKRI funding proposal entitled "CIVIC: Climate Impacts on Vectors in Cities". With a warming climate and increasing number of extreme weather events such as heatwaves, the risk of tick-borne diseases in the UK is expected to increase. CIVIC will investigate climate-mediated changes in vector-borne disease risk in urban green spaces and evaluate best approaches to increasing public understanding of risk and adaptation. This ALSPAC project will be important to achieve the objectives of CIVIC through understanding the cohort's perception, lived experience and behavioral adaptation to heatwaves and tick exposure.
B4651 - Health behaviours and pregnancy related mental health - 04/07/2024
We know that health behaviours during pregnancy (e.g., diet and physical activity) can impact on health outcomes (e.g., gestational diabetes). However, less is known about the impact of varying health behaviours on mental health outcomes (e.g., perinatal depression), and how the behaviour change of (reducing or increasing) these behaviours may impact perinatal mental health. This project will use traditional and causal epidemiological methods to investigate the impact of alcohol, tobacco and physical activity during pregnancy on maternal mental health using two longitudinal birth cohorts, to highlight pregnancy timepoints to reduce harm.
B4652 - Menopause So what A holistic approach on Hot Flushes Economic Choices Psychological Measurements and Health Conditions - 19/07/2024
Millions undergo yearly biological change, shrouded in misinformation and taboo, with minimal understanding of its impact on their economic decision-making (1). This is how life looks like for menopausal women, who experience a physical, emotional, mental, and social well-being transformation (2). Menopause is 'the permanent cessation of menstruation due to the decline in ovarian follicular activity' (3), broadly also including Peri- and Postmenopause. It causes symptoms like poor cognitive performance (brain fog), hot flushes, low mood, anxiety, and difficulty sleeping (2).
Until now, research focused solely on biology and medicine in the context of menopause, neglecting economic decisions and their complex interplay with hormonal changes, emotions, and biases (see, e.g., (4)). This project is the first to bridge this gap by applying a behavioural economics lens, delving into how menopause influences decision-making besides well-being and health outcomes. With nearly half the global population female (5) and the projected rise of 1.2 billion menopausal women by 2030 (6), understanding the economic implications of menopause matters - for women, society, policymakers, and businesses, as, e.g., menopause reduces women's economic participation (7), the menopause market is expected to be worth $24.4 billion by 2030 (8), and public interest is rising (9).
This project uses economic, psychological, and health data to study holistically how menopause affects women's economic decisions. Understanding economic decisions is fundamental to individuals, institutions, and society, demanding closer examination of underlying biological and psychological factors caused by menopause like hormonal shifts, brain-structure changes, depression, and genetic backgrounds (10; 4; 11). Our project utilises innovative economic experiments by simulating real-world economic scenarios and providing monetary incentives. This method is supplemented by health surveys and genetic data to understand how menopause influences women's economic choices (risk, investment, etc.). The goal is to develop targeted interventions based on our findings to empower menopausal women and improve their lives.
Working with the Avon data is central to our project. We will use the funding we currently apply for to collect data on economic behaviour (a central agenda of the project) and link it to genetic data as well as other health data captured in the Avon database. Understanding how menopausal women make economic choices is especially important, as menopause involves, e.g., financial changes like retirement planning and investment decisions. For example, when it comes to risky behaviour, we hypothesise that menopausal women are more risk-averse due to hormonal changes compared to women during their productive years and men older than 40. We will measure behaviour using the established questions from the preference module and compare the behaviour of menopausal women to people of other age groups and genders.
The preference module is a concise, experimentally validated survey designed to measure risk aversion, time discounting, trust, altruism, and positive and negative reciprocity. These preferences influence individuals' choices across various situations. This module provides standardised measures suitable for all popular data collection methods, making it a valuable tool for numerous applications. Preference measures enhance the prediction of significant economic behaviours and can serve as control variables for identifying causal effects of other factors correlated with preferences.
The development of the preference module is detailed in:
Falk, Armin, et al. "The preference survey module: A validated instrument for measuring risk, time, and social preferences." Management Science 69.4 (2023): 1935-1950.
Menopause and its transition occupy a significant portion of a woman’s life (13). This project offers a timely and cutting-edge approach, promising impactful results that improve lives, inform policy, and empower women to thrive through all stages of their journey.
1. The demography of menopause. Hill, Kenneth. 113-127, : Maturitas, 1996, Vol. 23.2.
2. NHS. NHS. Symptoms Menopause. [Online] 17 May 2022. https://www.nhs.uk/conditions/menopause/symptoms/.
3. WHO. Menopause. World Health Organization. [Online] 17 October 2022. https://www.who.int/news-room/fact-sheets/detail/menopause.
4. Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Mosconi, Lisa, Valentina Berti, Jonathan Dyke, Eva Schelbaum, Steven Jett, Lacey Loughlin, Grace Jang et al. 2021, Scientific reports, p. 10867.
5. The World Bank. The World Bank Data. Population, female (% of total population). [Online] 2022. https://data.worldbank.org/indicator/SP.POP.TOTL.FE.ZS.
6. Social Determinants of Health in Menopause: An Integrative Review. Namazi, Masoumeh, Sadeghi, Rasoul and Behboodi Moghadam, Zahra. 2019, International journal of women's health, pp. 637-647.
7. Brewis, Joanna, et al. The effects of menopause transition on women’s economic participation in the UK. s.l. : Department for Education, 2027.
8. Grand View Research. Menopause Market Size, Share & Trends Analysis Report By Treatment (Dietary Supplements, OTC Pharma Products), By Region (North America, Europe, Latin America), And Segment Forecasts, 2024 - 2030. [Online] 2024. [Cited: 18 February 2024.] https://www.grandviewresearch.com/industry-analysis/menopause-market#men....
9. Google Trends. Google Trends. Searching "menopause" Worldwide and for the UK. [Online] 15 February 2024. https://trends.google.co.uk/trends/explore?date=today%205-y&q=menopause&....
10. Elevated body temperature is associated with depressive symptoms: results from the TemPredict Study. Mason, Ashley E., et al. 1884, s.l. : Scientific Reports , 2024, Vol. 14.1.
11. An experiment on risk taking and evaluation periods. Gneezy, Uri and Potters, Jan. s.l. : The quarterly journal of economics, 1997, Vols. 112.2, 631-645.
12. National Office for Statistics. Office for National Statistics. National life tables – life expectancy in the UK: 2018 to 2020. [Online] 23 September 2021. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarri....
13. Brains, hormones, and genes: Introduction to the special issue on the biological foundations of economic decision-making. Fairley, Kim, Fornwagner, Helena and Okbay, Aysu. s.l. : Journal of Economic Psychology, 2023, Vol. 102683.
B4650 - The glue that holds the pieces together Unlocking Cognitive Health in Psychotic Disorders - 15/07/2024
Psychotic disorders like schizophrenia have a strong neurodevelopmental component, yet symptoms often do not emerge until adolescence or early adulthood. Cognitive impairments are among the earliest and most disabling symptoms. Intriguingly, our research reveals that many brain alterations linked to these impairments resemble those associated with premature aging, such as brain atrophy and advanced brain age. Understanding the neurodevelopmental pathways of these cognitive impairments is crucial for creating effective early interventions.
Our aim is to combat cognitive impairment in psychotic disorders as early as possible by:
1) Understanding the developmental features of brain age acceleration in psychotic disorders and what risk factors might exacerbate these, using large-scale neuroimaging datasets and computationally advanced methods;
2) Characterising the neuronal changes associated with advanced brain age, using experimental mouse models for schizophrenia;
3) Identifying treatment targets that could prevent or slow down cognitive impairment in psychotic disorders, using longitudinal proteomic samples (of individuals who later went on to develop psychosis).
Our goal is to unravel advanced brain age at a neuronal level, embed this within a neurodevelopmental framework, and identify effective treatment targets for early intervention against cognitive impairments in psychotic disorders to mitigate cognitive impairments at the earliest stages of the disease.
B4649 - Investigating associations between religion/spiritual beliefs and behaviours and brain MRI variables - 28/06/2024
Religiosity and spirituality are an important factor in the lives of many people. Previous research, using relatively small sample sizes in cross-sectional studies, has found that a high degree of belief in the importance of religion/spirituality was associated with both a thicker cortex and a larger pial surface area in persons at high risk for familial depression. We plan to see if these specific findings replicate in a much larger cohort. We also plan to do an exploratory analysis, where we will look at all of the brain MRI variables measured in ALSPAC to see if any are associated with the religion/spirituality variables measured in ALSPAC.
B4646 - Association between Locus of control and disordered eating - 24/06/2024
Locus of control is described as the way an individual perceives the outcome of events in their life as caused by their own actions (internal) or caused by outside factors uncontrolled by them (external). Research has linked locus of control, particularly external locus of control, with psychopathology, such as depressive symptoms, social anxiety symptoms, and psychotic-like experiences.
There is some evidence indicating that it may also be a risk factor for eating disorders. However, this research is mostly cross-sectional so it can't be ruled out that external locus of control is a consequence of eating disorders. To date, there is a lack of longitudinal research on this association, which limits our understanding of whether there is a causal association.
The present study aims to bridge this gap in the literature by investigating the association between external locus of control in childhood at age 8 and eating disorder symptoms in adolescence at age 16.
B4645 - Development of symptoms of emotional problems from childhood to adolescence a longitudinal network analysis - 27/06/2024
The project aims to describe the development of different specific emotional problem symptoms from childhood to adulthood and how different symptoms are related to each other and influence each other over time. The project will also examine whether girls and boys show differences in these developmental patterns.
B4647 - Coeliac Disease in the Children of the 90s - 04/07/2024
Coeliac disease is a chronic illness that often begins in childhood. It is an autoimmune disorder, which means the body's immune system incorrectly attacks healthy tissues, causing inflammation. In coeliac disease, this attack occurs in the gut when gluten—a protein found in wheat and other grains—is consumed. About 1% of people have coeliac disease.
The symptoms of coeliac disease can range from minimal to no symptoms in some people, to vague symptoms often seen in childhood such as stomach upset, diarrhoea, fatigue, or poor growth. These symptoms can also be found in other illnesses, which makes it challenging for doctors to decide on the necessary tests or whether to refer a child to a specialist for a confirmed diagnosis. Delays in diagnosing coeliac disease can lead to delays in treatment and result in worse health outcomes, such as poor growth, weakened bones, and an increased risk of certain cancers.
Our team has performed a review of all the research looking at what is linked with a higher risk of getting coeliac disease in children. From this other work, breastfeeding was linked with lower rates of coeliac disease in some studies, and antibiotic use in early childhood was sometimes linked with a higher risk of coeliac disease.
In our proposed study, we will use data from the "Children of the 90s" cohort to examine whether breastfeeding and the use of antibiotics might be linked to the risk of developing coeliac disease along with associated GP/hospital records. We will employ statistical methods to analyse data from this cohort to determine whether breastfeeding may help to decreases the risk of developing coeliac and if use of antibiotics in young children is linked with an increase in coeliac disease.
What we learn from this project may be able to help doctors in knowing what questions to ask to understand which children are at risk for coeliac disease. This could help with making the diagnosis of coeliac disease as early as possible. This information will also be valuable for informing the guidelines on breastfeeding and antibiotic prescribing.
B4642 - Meta-analysis of COVID-19 Vaccine Genetics - 20/06/2024
During the COVID-19 pandemic, vaccination efforts were crucial in controlling the spread of SARS-CoV-2. While we know from previous studies that factors including older age, immunosuppression, and obesity contribute to a reduced response to vaccination and increase the risk of breakthrough infection. Host genetic variability is increasingly appreciated to contribute to vaccination variability but contemporary studies lack power and diversity of immune measure and participant inclusion to truly understand the contribution and mechanism of genetic effects. By using statistical genetics approaches this project aims to better understand the role genetics plays in determining response to COVID-19 vaccines in different populations. This analysis may provide valuable insights into the factors influencing vaccine efficacy and inform future vaccine design and deployment strategies worldwide.
B4643 - Identifying children at risk of persistent speech sound disorder - 20/06/2024
This work is the first stage in developing a tool to identify young children who are at risk of having problems with their talking. This is important because getting help early means that their difficulties do not make it harder for them to learn at school or to make friends. In this study we will use the data to help us work out which information is needed to make the tool work effectively. In the next stage of this work, we will ask young people, parents and people who work with children to help us design how the tool will look and function. This will mean that it works in a way that is most useful for the people who are going to use it.
B4640 - Sex differences in association of maternal age with trajectories of cardiometabolic risk factors across childhood and adolescenc - 19/06/2024
Maternal age is increasing globally. We aim to examine whether maternal age is associated with trajectories of cardiometabolic risk factors as previously modelled by us across childhood and adolescence with a particular focus on whether there is any evidence for sex-specific associations.
B4641 - B3568 - The genetics of speech sound disorder - 18/06/2024
There is variation in when and how children develop speech in early
childhood. Some children experience difficulties in the process but many
of these have speech which is well developed by the time they start
school. Some children have persistent problems which continue into early
childhood. These problems can be associated with problems with
educational attainment in older childhood as well as having difficulties in
making themselves understood. Some of these children will have
problems with their speech as a result of subtle problems with the
coordination of the movements required for speech while others will
have difficulties associated with the cognitive skills involved in developing
speech. Some will have problems with both.
Genes have been identified which are associated with some types of
speech and language difficulties but it is not yet clear what part genes
may play in persistent speech sound disorder. The analysis outlined in this
proposal will enable us to determine to what extent children's problems
with speech after they have started school may be associated with
genetic factors rather than environmental factors. This information will
help us identify how best to help children who present with these
difficulties to speech and language therapists and in school.
B4636 - Identifying opportunities to improve lifecourse outcomes for children requiring general anaesthesia for the removal of decayed - 02/07/2024
Children attending for dental extractions due to tooth decay asleep are a known at risk group for other non communicable diseases (NCDS) such as obesity, diabetes and heart disease. Could a health intervention for this cohort of potentially vulnerable children improve their health outcomes in early adult hood. This project will be look at data from a Bristol based birth study to see if there are differences in adult health outcomes such as mental health, obesity, breathing disorders and employment compared to children who did not need to go to sleep for dental extractions.The aim is to identify if their is a need and ultimately an opportunity for intervention to improve general and social health for a population.