Proposal summaries
B4773 - Uncovering social and biological mechanisms between heat and mental health in pregnancy and across early life - 19/12/2024
Adult mental health is different depending on the season in which someone is born, which suggests that heat during pregnancy might affect later life mental health. While there is already lots of research into how mental health conditions can be influenced by difficult events in their earlier life, the long-term effects of heatwave exposure on anxiety and depression in mothers and their children are not yet well understood. This is in part because of the challenging data required to understand this better. For example you would need to do long studies over time across big groups of people.For this research proposal, we want to understand what social and biological factors related to heat exposure at early life and during pregnancy can lead to anxiety and depression in pregnant mothers and their children.
B4768 - Lung Function COPD Epigenetics and Accelerated Ageing Across the Lifespan - 11/12/2024
Chronic Obstructive Pulmonary Disease (COPD) is a complex, heterogeneous and prevalent disease with a high socio-economic burden whose underlying biological mechanisms are unknown. It is now well established that about half of the patients with COPD never achieved a normal lung function early in life, and there is increasing evidence that some COPD risks may derive from early life factors in this setting it is highly likely that respiratory diseases are the end result of a set of different dynamic environmental-gene interactions that can occur during the entire life span of an individual (time). Lung development and lung aging are often considered two independent phenomena, but they are tightly interrelated.
Here we propose that alterations during lung development influence age-related physiological deterioration and cause premature lung aging. We expect that the lung (lung tissue and bronchial biopsies), as affected organ in COPD, accumulates the highest burden of methylation changes, but that some of them, are reflected in the circulating blood. Subsequently we will explore if these changes are identifiable early in life. We sought to explore this hypothesis by comparing the epigenetic profile associated with FEV1
B4742 - Can the negative effects of low socioeconomic status on child cognitive development be negated by home environment factors - 09/12/2024
An abundance of previous research has demonstrated the damaging effects of low socioeconomic status (SES) on a child's emerging cognitive skills, and this leads to an achievement gap which exists by the time children enter school; a gap which continues to widen throughout the school years. Building on previous findings that have suggested that some factors, such as neighbourhood chaos, may have a protective effect against the detrimental effects of low SES, this study aims to investigate whether certain parenting styles and home environment factors may negate the effects of SES on child cognitive development and subsequent school achievement. These will include control parenting, warmth parenting, distracting parenting, background noise parenting, parental verbal and non-verbal engagement with children, physical proximity parenting, child mental health, and parental cognitive ability. By investigating these potentially mediating factors, we hope to shed light on ways of supporting the cognitive development of disadvantaged children.
B4772 - Epigenetic Biomarkers of Immune Activation in Mental Health Trajectories - 09/12/2024
Previous research has shown that epigenetic markers, like DNA methylation, reflect environmental exposures and can predict disease outcomes. The immune system is known to be involved the development of mental health problems and is one of the main body systems that regulates the response to various environmental risk factors. Therefore, the epigenome of immune cells could carry valuable information about the role of the immune system in mental health. Recent studies show that epigenetic markers of inflammation outperform circulating inflammatory protein levels in predicting inflammation-related diseases, due to their higher temporal stability, which may better capture chronic inflammation. Also, epigenetic processes are involved in developmental programming of both the immune system and nervous system, making epigenetic markers attractive for studying developmental origins of immune-related mental health risk. When applying such epigenetic markers in research on the immune-mental health link, developmental stages need to be considered, to elucidate epigenetic timing effects. With this project, we aim to explore the potential of epigenetic biomarkers to study how immune activation throughout development contributes to the risk of mental health problems, as a potential resilience mechanism in response to environmental risk factors.
This project is embedded in the Youth-GEMs project, an european consortium on gene-environment interactions in mental health trajectories of youth (ALSPAC proposal B3879).
B4775 - Intergenerational Trajectories of Depression Maternal Mental Health Genetic Susceptibility and Family Dynamics - 09/12/2024
There is a growing body of evidence suggesting that maternal depression during pregnancy and the postnatal period can have profound and lasting effects on the mental health of offspring, particularly in terms of depression. This study aims to explore the intergenerational trajectories of depression, focusing on the role of maternal mental health, genetic susceptibility, and family dynamics as potential mediators and moderators in the transmission of depression from mother to child.
Building on previous research that has established a link between maternal depression and offspring mental health outcomes (Goodman et al., 2018), this project will employ a longitudinal approach to examine the trajectory of maternal depression and its influence on the development of offspring depression. We will explore the genetic underpinnings of depression by incorporating genetic risk scores (GRS) to assess the genetic liability within families. This approach allows us to understand not just the environmental transmission but also the genetic contribution to the intergenerational pattern of depression.
The study will also investigate the mediating role of family dynamics, such as parenting practices and the parent-child relationship, in the association between maternal depression and offspring depression. The impact of paternal involvement and the couple relationship quality on maternal postpartum depression and child development will be considered.
B4774 - Impact of Early Childhood Free Sugar Consumption on Childhood and Adolescent Obesity and Cardiometabolic Risk - 09/12/2024
Our team has previously utilized ALSPAC data and published findings suggesting that a) maternal nutritional status during pregnancy and b) free sugar intake at age 3 years are both positively associated with hepatic steatosis in young adulthood.1,2 We would like to extend our research to examine associations between early life free sugar and sugar-containing beverage consumption at 18 months and obesity and cardiometabolic risk throughout childhood and adolescence. Building off our earlier findings related to maternal nutritional status, we will also examine effect modification of the free sugar and later obesity association by maternal metabolic dysfunction and diet during pregnancy.
Increasingly, research has implicated early childhood as a critical window for the establishment and maintenance of obesity, necessitating a focus on preventing obesity early in life. Consequently, it is critically important to develop a better understanding of early life dietary factors that increase obesity risk. Current infant and toddler dietary recommendations include a focus on minimizing free sugar consumption as excessive intake may predispose children to obesity, but the evidence underpinning these guidelines is limited. It is unclear what amount of free sugar intake during early life conveys increased risk of obesity and compromised cardiometabolic health, and what factors modify this risk. Further, maternal metabolic dysfunction during pregnancy is associated with increased risk of offspring chronic disease via in-utero metabolic programming, and recent research has suggested that an interplay may exist between the prenatal environment, early nutrition, and later cardiometabolic health. However, to date, no researchers have examined how the early free sugar-childhood obesity relationship may be modified by maternal conditions such as pre-pregnancy obesity, excessive gestational weight gain, and gestational diabetes. A better understanding of the potential effect modification by maternal health during pregnancy could help provide insights into which, if any, groups may benefit from increased, targeted early life nutrition guidance. We will utilize longitudinal data from a British birth cohort study (Avon Longitudinal Study of Parents and Children) to assess the association between free sugar and sugar-containing beverage consumption at 18 months and obesity at ages 5, 7, 13, 15 and 17 years and cardiometabolic risk at ages 15 and 17 and examine effect modification of the associations by maternal metabolic dysfunction and diet during pregnancy. Our findings will inform existing infant and toddler nutrition guidelines and help guide the development and targeting of early childhood obesity prevention interventions.
Publications from original proposal:
1. Sekkarie A, Welsh JA, Northstone K, Stein AD, Ramakrishnan U, Vos MB. Associations between Free Sugar and Sugary Beverage Intake in Early Childhood and Adult NAFLD in a Population-Based UK Cohort. Children. 2021; 8(4):290. doi: 10.3390/children8040290
2. Sekkarie A, Welsh JA, Northstone K, Stein AD, Ramakrishnan U, Vos MB. Associations of maternal diet and nutritional status with offspring hepatic steatosis in the Avon longitudinal study of parents and children. BMC Nutr. 2021;7(1):28. Published 2021 Jul 8. doi:10.1186/s40795-021-00433-3
B4761 - Investigation of the utility of transcriptomic and epigenetic data for diagnosing the onset of puberty - 06/12/2024
Growth and Puberty are fundamental aspects of childhood development. Puberty is the period of transition between childhood and adulthood, resulting in the capacity to reproduce and is associated with a significant increase in rate of growth. The mechanisms underlying the control of human growth as well as initiation of human puberty are poorly understood. Knowledge of the mechanisms, as well as being of great interest, could contribute to the care and treatment of children with early and late puberty. The proposed study aims to further understanding of the control of childhood growth and triggers of pubertal onset using measures of gene activity in normal children from the ALSPAC cohort. By examining the pattern of growth and puberty in normal children and comparing this with patterns of gene activity, we hope to identify markers of pubertal onset and identify which genes influence growth rate. We aim to use this information to develop a blood test for use in children with possible disorders of puberty.
B4770 - Exploring Transdiagnostic Trajectories in Youth Mental Health The Role of the Genome and Exposome - 06/12/2024
This project aims to improve our understanding of how mental health conditions emerge and develop during childhood, adolescence and early adulthood. By studying the interplay between biological and environmental factors, we aim to uncover how these influences can either contribute to drive or prevent the onset of mental ill-health. This research is part of the Youth-GEMs project, a European consortium dedicated to investigating gene-environment interactions in the mental health trajectories of young people (ALSPAC proposal B3879).
B4771 - MODELLING THE ECONOMIC CONSEQUENCES OF CHILDHOOD ANXIETY PROBLEMS - 09/12/2024
This research will adopt a life course approach to the assessment of child mental health outcomes and associated costs. Primary analyses of the Avon Longitudinal Study of Parents and Children (ALSPAC) will be conducted to identify the natural history of child anxiety problems into early adulthood, and quantify their lasting effects - over the life cycle - in terms of educational attainments, adult health, employment and, if possible, associated health and social care use, and productivity costs.
B4769 - Hormones rhythms and responses Exploring the role of aldosterone obesity and hypertension in young people - 17/01/2025
The number of young people (aged under 40) being diagnosed with high blood pressure is increasing. Patients with high blood pressure are often overweight or obese and together this substantially increases their risk of cardiovascular and metabolic diseases. At the moment, mechanisms linking obesity and hypertension in young people are not very well understood but abnormalities in a hormone called aldosterone have been associated with both pathologies. There is increasing evidence that the contribution of aldosterone to blood pressure and cardiovascular disease is substantially under recognised. This project proposes to recruit participants in the ALSPAC cohort to perform a short but high-dimensional observational study. I will use a non-invasive biological sampling technique called microdialysis to measure the dynamics of aldosterone in relation to sleep, activity, posture, and internal body rhythms in obese people with and without hypertension, and in a non-obese control comparison group. Access associated phenotype and longitudinal data related to blood pressure and other parameters from ALSPAC will provide enormous extra value.
B4767 - Enhancing Genetic Insights Through Longitudinal Analysis and Novel Statistical Tools - 06/12/2024
Complex human genetic disorders are major contributors to global morbidity and mortality. Understanding their underlying pathophysiology is essential for advancing treatment and prevention. These disorders have heritability estimates between 40-80% and are considered polygenic, involving the interplay of multiple genes alongside environmental influences. This complexity complicates efforts to understand causal factors and disease mechanisms, predict individual susceptibility and uncover the molecular mechanisms involved, both of which are critical to improving treatment options. Genome-wide association studies (GWAS) have uncovered numerous trait-associated single nucleotide polymorphisms (SNPs) in diverse complex phenotypes. However, existing methods largely overlook the dynamic interactions between genetic and environmental factors over time, limiting our ability to fully understand and predict the progression of complex human disorders. This proposal aims to utilize ALSPAC data to investigate the genetic architecture of human traits, with a focus on the complex interplay among genetic factors and environmental influences, in mental disorders and co-morbid conditions. Leveraging ALSPAC’s rich longitudinal data, we will analyze SNPs linked to both baseline and longitudinal phenotypes and their changes over time, advancing our understanding of the dynamic genetic and environmental contributions to the development and progression of these traits.
B4764 - Exploring the Impact of Poverty on Child Well-being A Longitudinal Analysis of Mental Health and Criminal Behaviours - 05/12/2024
People who experience early life family financial hardship are more likely to encounter mental health challenges and engage in criminal behaviours during adolescence. However, fewer studies have explored how these outcomes in adulthood are influenced by early family financial hardship, especially criminal behaviour. Interestingly, while most people’s criminal behaviours peak during mid- to late-adolescence and diminish during early adulthood, a small proportion of individuals continue involvement in criminal behaviour during adulthood. Understanding the extent of this criminal behaviour continuation and how it is influenced by early life family financial hardship is important but under researched.
Previous studies tend to measure family socioeconomic status (usually with family income, parental education and occupation) and its association with later outcomes. This broad concept could potentially lead to oversimplification, whereas examining financial hardship alone allows for a more targeted analysis, shedding light on the specific challenges posed by economic constraints and their direct impact on offspring mental health and criminal behaviours. Moreover, it is important to distinguish between people’s feeling about their financial situation and the actual financial figures, as these perspectives can influence outcomes differently. Having a precise measurement for exposures can provide reliable conclusions for our findings and can promote more effective interventions and utilisation for public policy.
Previous studies have shown parental mental health and parenting styles influence the effects of family financial hardship on offspring (Devenish et al., 2017). However, fewer studies have explored how adolescents’ self-esteem, which indicates how people feel about themselves, can influence associations between family financial hardship with depression and criminal behaviour in adulthood, despite strong evidence for associations between self-esteem and mental health (Keane & Loades, 2017).
Comparing with early life financial hardship, more recent economic stresses can also impact young people’s wellbeing (Dunn et al., 2018). Given that many people live away from their parents and have their own work/study, their own financial situation can also associate with their mental health outcomes and potential engagement of criminal behaviours. Therefore, how adulthood financial situation relates to young adults’ mental health and criminal behaviour, is also an important avenue for research.
B4766 - Using Shopping Data to Explore the Impact of COVID-19 on Mental Health - 12/12/2024
This project will use shopping data to explore COVID-19's impact on mental health. Previous research (Kwong et al., 2020) showed increased anxiety for ALSPAC participants during the pandemic, while depression remained stable. We build on this by introducing novel behavioural data from loyalty cards, which offer detailed, objective insights into individual purchasing behaviours. Supermarket data captures individual behaviours through the purchase of food, alcohol, tobacco, and over-the-counter medications—key indicators of coping mechanisms during periods of stress and anxiety (Jia et al., 2020). This project will look at purchase patterns before, during and after the pandemic. We will compare these purchasing patterns with mental health data from self-reports and medical records, enabling us to better understand the breadth and long-term effects of COVID-19 on population mental health.
Kwong et al. (2020): Mental health before and during the COVID-19 pandemic in two longitudinal UK population cohorts - PMC (nih.gov))
Jia et al. (2002): Mental health in the UK during the COVID-19 pandemic: cross-sectional analyses from a community cohort study
B4757 - Investigating the contributions of fetal and maternal genetic variation in GDF15 in nausea vomiting and hyperemesis gravid aru - 02/12/2024
References to previously published work in the summary below are given as
PubMed IDs.
Nausea and vomiting during pregnancy (NVP) is estimated to occur in around 70%
of women globally, with 1.1% of women estimated to experience severe cases,
diagnosed as Hyperemesis Gravidarum (HG) (PMID: 23863575). HG is associated
with dehydration and weight loss, which can result in hospitalisation and have
significant detrimental effects for both mother and fetus. These include increased
risk of morbidity, placental complications, small for gestational age birth, maternal
psychological distress and increased risk of developmental delay for offspring
(PMID: 35367190, PMID: 25898368, PMID: 23360164, PMID: 33713683, PMID:
21413857) .
A recent study (PMID: 38092039) made great progress in understanding a major
cause of NVP and HG. Using a variety of analyses, especially of human genetic
data, the authors showed that maternal sensitivity to a protein released from the
placenta called growth differentiation factor 15 (GDF15), is key causal risk factor.
This finding was exciting as it suggested avenues for future research into
prevention or treatment. Evidence for the role of GDF15 included associations of
variants (single letter changes in the DNA code) in the GDF15 gene region with
both risk of NVP or HG, and with GDF15 levels in the blood (PMID: 35218128,
PMID:29563502, PMID: 38092039). The finding that women who have naturally
low levels of GDF15 are more sensitive to the GDF15 released from the placenta
and more susceptible to NVP and HG, raised the possibility that a fetal genetic
variants which increase GDF15 production may also influence HG or NVP risk.
There was some evidence in a small sample that the genotype of the fetus, relative
to the mother, may be associated with the proportion of fetal-placental derived
GDF15 contributing to circulating GDF15, potentially mediating experiences of
nausea and vomiting (PMID: 38092039). However, analyses of maternal and fetal
genotype data in well powered samples are needed to confirm this, which is the
focus of our proposed project. We aim to explore the maternal and fetal genetic
contributions of genetic variants to nausea and vomiting during pregnancy.
B4758 - The impact of intergenerational transmission of mental health problems on childrens development in early life - 02/12/2024
Mental health problems can run in families, and children with parents or grandparents who struggle with mental health are at a higher risk of facing challenges in their development. For example, when parents or grandparents have mental health problems, it can sometimes lead to poorer outcomes for children. However, it’s not yet clear whether this is due to a general pattern of mental health issues or due to specific mental health conditions only. We also don’t fully understand whether some aspects of a child’s development, like their behaviour, health, or learning, are more affected than others. Importantly, not all children with a family history of mental health problems will have developmental issues. Therefore, it’s crucial to figure out what helps protect children and build resilience against these risks. To explore this, we are using data from the ALSPAC, which includes information on three generations: grandparents (G0), parents (G1), and children (G2). We aim to find out if children with a family history of mental health problems are more likely to face challenges in early childhood, such as having a difficult temperament, poor health, behavioural issues (like trouble sleeping), or delays in language development.
B4763 - Epidemiology and aetiology of Avoidant Restrictive Food Intake Disorder - 19/12/2024
Avoidant Restrictive Food Intake Disorder (ARFID) is a severe eating disorder that causes people to avoid certain foods or limit their intake. Unlike other eating disorders, ARFID isn’t about body image—it can stem from low appetite, sensory sensitivity to textures and smells, or a fear of choking or vomiting. Affecting around 1–2% of the population, ARFID can lead to malnutrition, health complications, and significant distress.
Our research focuses on understanding ARFID’s causes and how it varies between individuals. We aim to answer big questions: Is ARFID primarily a neurodevelopmental condition, an anxiety disorder, or influenced by physical health issues? Are there distinct subtypes of ARFID requiring different treatments? What are the genetic, environmental, and developmental risk factors for ARFID, and do these differ by subtype?
To explore these questions, we will analyse ALSPAC data, alongside data from the Norwegian MoBa cohort and the Born in Bradford cohort, and work closely with people living with ARFID, healthcare providers, and the eating disorder charity Beat. By involving those with lived experience at every stage, we will ensure our findings are relevant and impactful.
This project will help identify new approaches to diagnosing and treating ARFID, creating evidence-based tools for clinicians and improving support for those affected. With ARFID research in its early stages, this work is crucial to advancing our understanding and shaping better services.
Our goal is to bring real-world benefits to individuals and families struggling with ARFID, ensuring they receive the care and support they need.
B4762 - Preparation of new and updated NMR data for general release - 02/12/2024
Nuclear Magnetic Radiation (NMR) Data assesses systematic metabolites in blood samples at 4 exiting time points in the ALSPAC cohort (G1); age 7, age 15, age 18, and at age 24. 229 metabolites were quantified (149 concentrations plus 80 ratios derived from these) including cholesterol, triglyceride, and other lipid content in lipoprotein subclass particles (very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL)), apolipoprotein-B and apolipoprotein-A-1, fatty acids and amino acids, and inflammatory glycoprotein acetyls (Bell et al 2021). There are two new updates to this data:
1- Update to data: The latest version of Nightingale Health's NMR data (Quantification library version 2020), has been improved to provide more accurate measurements. These updates ensure that the concentration levels of various biomarkers better align with those measured by clinical tests and other laboratory methods. Additionally, the data used to calibrate lipoprotein subclasses (key indicators of cholesterol and cardiovascular health) has been extended. This updated version is identical to the dataset used for analysing UK Biobank's 500,000 plasma samples between 2021 and 2024.
2- New time point at age 30: Along with the already existing timepoint in the ALSPAC NMR dataset, a new timepoint is now available at age 30
The aim of this project is to prepare the new and updated data for general release.
B4756 - Pilot analyses for Fellowship application related to cognitive change in ALSPAC G0 mothers and partners - 29/11/2024
This project is for conducting pilot analyses for Fellowship applications (e.g. Wellcome/MRC Career Development Awards) that I will be submitting in the area of cognitive change in ALSPAC G0 mothers and partners. Primarily, I will be calculating numbers of participants who have data on potential exposures (e.g. genetics, DNA methylation, proteomics and metabolomics) and potential outcomes (e.g. cognitive data), to see if planned analyses are feasible.
B4755 - Predictive Power of BMI-PRS Across Different Life Stages A Central Step in Understanding the Genetic Basis of Obesity - 29/11/2024
Our genetic makeup, which is stable across life, influences our health and can serve as an early risk indicator for various diseases. Precise genetic tests exist for single-gene diseases, but common and complex conditions like obesity result from the subtle effects of many genes. We use Polygenic Risk Scores (PRSs) to assess comprehensive genetic risk for diseases or traits, encompassing many (hundreds to millions of) genetic variants. For BMI, for which high values can present a significant health concern, a PRS containing 941 common genetic variants influencing adult BMI has been established using UK Biobank data. However, these genetic variants are identified in mostly adult populations (> 50 years), and their performance in other age groups has been less well established. The transition from normal to high BMI and its onset at various life stages, particularly from childhood to adulthood, remains complex and warrants deeper exploration.
B4759 - VirScan Assessing viral epidemiology over the pandemic period in ALSPAC - 16/01/2025
Viruses are ubiquitous pathogens that cause innumerable infections each year in humans. Many infections are sub-clinical or only result in mild symptoms, while some result in serious clinical illness. There is a well recognised seasonality to many viruses and there is a complex interaction between behaviour, exposure, season, and circulating strains that means that viral epidemiology is complex. VirScan is a new technique that allows for simultaneous measurement of exposure to all known human viruses in a single human sample. This technique means that we can identify the 'infection history' of a given individual based on one serum sample. In this proposal, we aim to use this VirScan technology to profile the response of ALSPAC participants to viruses over the period of the COVID-19 pandemic. This will allow us unique insight to the changes in viral epidemiology over this time period, and answer key questions about the durability of infection response and how viral epidemiology changed over this time period. A comparator analysis will be performed in TwinsUK to compare and contrast.