Proposal summaries
B4191 - EWAS of Green Spaces - LifeCycle - 22/11/2022
PLEASE NOTE ALL OF THE FOLLOWING SECTIONS ARE COPIED AND PASTED FROM A PREVIOUSLY APPROVED PROJECT THAT IS IDEANTICAL TO TO THIS - B3549. WE HAVE HAD TO SUBMIT AS A NEW PROJECT TO ACCOMODATE CHANGE TO THIS NOW BINE A PHS MINI PROJECT
The urban exposome (built environment, air pollution, road traffic noise, meteorological, natural space and road traffic) affects health outcomes. For instance, associations between increasing green space exposure and increased birth weight and decreased term low birth weight in 32,000 mother-child pairs have been previously reported (Nieuwenhuijsen et al. 2019).
Here we aim to investigate the epigenetic mechanisms that might mediate this association. We will evaluate the relationship between exposure to green spaces during pregnancy and offspring cord blood DNA methylation at over 450,000 methylation sites (CpG sites) across the genome. This project will contribute epigenome-wide association study summary results to a meta-analysis as part of an ongoing large consortium.
B4205 - The intergenerational links between PRS of ADHD in mothers and childhood maltreatment in their children - 06/12/2022
Childhood maltreatment has a profound impact on both the short- and long-term wellbeing of children. Specifically, children with autism and those with attention deficit/hyperactivity disorder have a higher risk to experience maltreatment than those with typical development. However, the reasons why this is happening, are unclear. Two studies will be conducted. The first study will investigate the relationship between childhood maltreatment and ADHD. Studies support an association between ADHD and maltreatment: Children with ADHD have higher risk of experience maltreatment than those without ADHD, as well as people who suffered childhood maltreatment have high levels of ADHD symptoms and diagnosis. Also, parental ADHD and/or experience of maltreatment could influence the strength of this association. So, we will define and analyse how genetic and social factors affect the association between ADHD and childhood maltreatment, and then how this could be developed through generations. Having assessed and display the association between ADHD and childhood maltreatment, the second study will go a step forward searching the experience of physical abuse and harsh parenting in children with ADHD and children with autism. We will conduct a comparison between children with ADHD and children with autism trying to understand how the different traits of each condition may affect different the risk of physical abuse and harsh parenting.
B4199 - The impact of command hallucinations and delusions of thought interference on suicidal behaviours - 21/11/2022
Auditory verbal hallucinations are conceptualised as hearing voices or a sense of being communicated to without any external speaker present. Historically viewed as hallmarks of psychosis and other serious mental illnesses, we now know that nonclinical voices can occur with varying intensities and frequencies in the general population too. However, clinical voices such as those of a commanding nature often contribute to severe levels of distress and dysfunction, especially when the voices command the voice-hearer to carry out harmful actions against their will. Related phenomena, called delusions of (thought) interference, include thought insertion and delusion of control, defined as the feeling that someone external is sending or forcing thoughts into a person's mind and being under the influence of an external power, respectively. Command hallucinations, delusion of control and thought insertion breach if not erase the boundary between one's self and other, thus leading to a confusion between internal and external events which can make the commands exceedingly difficult to resist. Sometimes both the distress caused by and the coercive nature of such experiences can lead to suicidal feelings and behaviours including acts of self-harm. This project aims to investigate the relationships between such command hallucinations, inserted thoughts and suicidal behaviours by studying their trajectories, how they develop and change over time, as well as clarifying the impact of these experiences on individuals' mental wellbeing versus diagnoses of mental illness.
B4198 - Revisiting the associations between asthma and psychotic experiences - 21/11/2022
Asthma is a chronic condition influencing breathing and characterised by breathlessness, coughing and chest tightness. Asthma can be triggered by exposure to several allergens (e.g., pollen) or infections and is considered predominantly an inflammatory condition. There is increasing evidence suggesting that asthma in childhood may be linked to a number of adverse mental health outcomes including psychotic disorders such as schizophrenia and bipolar disorder. Specifically, previous studies using the ALSPAC resource have found evidence of associations between asthma at age 10 and psychotic experiences at age 13. Furthermore, studies using large nationwide data from Sweden, found that asthma in parents was associated with bipolar disorder in their children. The reasons underlying these associations are largely unknown and several explanations have been hypothesised. For example, it has been proposed that inflammatory mechanisms involved in asthma might be causal for psychotic disorders. Gaining a better understanding on the relationship between asthma and psychotic disorders can have important implications towards uncovering drug targets for these chronic mental health conditions.
B4200 - Plant-based diets iodine and neurodevelopmental outcomes - 21/11/2022
Iodine deficiency during pregnancy can result in impaired thyroid function and lead to altered brain structure. We have shown that even mild-to-moderate ID in UK pregnant women is associated with lower child IQ and reading scores at age 8-9 years.
Recent dietary recommendations promote plant-based diets for environmental sustainability and such diets are increasingly popular, particularly among young women. Since plant foods have low iodine content and animal foods are the main contributors to iodine intake, plant-based diets may increase the risk of iodine deficiency. Such diets, with high vegetable intake, may also be high in goitrogens (foods that may reduce the absorption and use of iodine in the body). A diet high in goitrogens but low in iodine may increase the risk of ID and its effects on child neurodevelopment, but there is a lack of data in this area.
In this project we plan to investigate whether a dietary risk score that considers both iodine intake and iodine inhibitors can predict mother's iodine status and thyroid function in pregnancy, and also child cognitive outcomes (e.g. IQ).
B4196 - Epigenetic pathways to youth self-injurious thoughts and behaviours dissecting phenotypic heterogeneity and time course - 23/11/2022
Suicide is a leading cause of death among youth, but little is known about the associated risk factors. Growing recognition that the existing clinical and psychological measures do not predict suicidal behaviour very strongly has contributed to a focus on the genetic correlates and predictors of suicide risk. Although genotypes do not change across the lifespan, an epigenetic process known as DNA methylation is responsive to environmental experience and can modify the expression of certain genes. Although numerous investigations have cross-sectionally identified a role for DNA methylation changes in self-injurious thoughts and behaviours (such as suicide attempt, suicidal thoughts, and self-injury without suicidal intent), these studies have largely focused on adults. Given that development is associated with numerous biological, epigenetic, and psychosocial changes, there is a need to better identify specific DNA methylation risk factors in youth, rather than extrapolating from work in adults. In this project, we aim to conduct epigenome-wide association studies (case-control comparison of methylation at numerous locations in the genome) of suicide ideation; suicide attempt history; and self-injury without suicidal intent; in teenagers who are part of the Avon Longitudinal Study of Parents and Children. We will also be able to make use of methylation measurements taken in childhood and at birth to trace any methylation differences backward, in an attempt to understand when they might emerge. These findings will be essential to identifying youth-specific risk factors for suicide, and ultimately contribute to efforts to better inform risk assessment as well as biologically informed interventions.
B4197 - Early Life Factors and Childhood Metabolomic Profiles with Risk of Non-Alcoholic Fatty Liver Disease Fibrosis in Young Adults - 21/11/2022
Non-alcoholic liver disease (NAFLD) is the most common cause of liver disease among children and adults. NAFLD is a spectrum of disease which includes significant fat deposits in the liver, liver inflammation, and in some cases permanent scarring and cirrhosis. NAFLD is more common among individuals with obesity and metabolic syndrome. Current evidence suggests risk for NAFLD, obesity, and metabolic syndrome can be inherited and influenced by early life exposures. However, there is no framework for identifying who is at greatest risk for more severe liver disease (inflammation, scarring, cirrhosis). We aim to investigate whether development and severity of NAFLD in young adulthood is associated with blood markers of metabolism in childhood and parental factors.
B4189 - Methods to Detect and Adjust for Selection Bias - 14/11/2022
Biomedical research is often hindered by the presence of missing data. For example, missing data can occur due to study participants' unwillingness to disclose sensitive information about themselves (e.g. refusing to answer questions related to their mental health, smoking habits, alcohol consumption or drug use). In our research, we will develop novel statistical methodologies to assess the impact of missing data in epidemiologic studies, understand under which conditions the presence of missing data will bias an applied analysis, and overcome this form of bias.
B4192 - Assessing the robustness of multiple imputation strategies in practice - 14/11/2022
Around 14,000 children initially participated in ALSPAC. Over time, many children have been lost to follow-up (“drop-out”) or have participated at some time-points and not at others (“sporadic non-response”). Missing data due to non-response can lead to bias when estimating associations. Multiple imputation (MI) is an analysis strategy that can correct this bias, by recovering information about the missing values using observed variables (“predictors”). However, there are methodological challenges with the correct application of MI. The aim of this project is to assess their impact in practice, and develop an automated expert system to guide researchers through the multiple decisions required when using MI.
B4193 - Examining the aetiology of alcohol use in autistic adults - 14/11/2022
Alcohol use is a major issue for the UK healthcare system. Little is known about the link between autism and alcohol use, but preliminary research suggests that autistic adults who drink are twice as likely to become dependent as their neurotypical counterparts (1; 2). This does not seem to be the case for autistic adolescents (but existing studies are limited methodologically by small sample sizes and cross-sectional study designs) (3). Using longitudinal population-based studies to understand alcohol use in autistic adolescents going into young adulthood could address these issues. Doing this while controlling for potential confounders will help us understand what influences the development of this association over time.
Further, it is unclear whether genetics influence this association. Exposure-outcome associations are often estimated without accounting for genetic confounding in epidemiological studies, leading to potential inaccuracies (4). A genetic variant in the autism susceptibility candidate 2 gene (AUTS2) has been found to be associated with alcohol consumption (5), but it is unclear whether there are other genetic variants associated with autism that influence alcohol use. To assess this, we could calculate polygenic risk scores for autism and explore their association with alcohol use. This will help us ascertain whether genetic overlap plays a role in the aetiology of this association and potentially improve the accuracy of future causal estimates.
(1) Bowri, M., Hull, L., Allison, C., Smith, P., Baron-Cohen, S., Lai, M. C., & Mandy, W. (2021). Demographic and psychological predictors of alcohol use and misuse in autistic adults. Autism, 25(5), 1469–1480. https://doi.org/10.1177/1362361321992668
(2) Butwicka, A., Långström, N., Larsson, H., Lundström, S., Serlachius, E., Almqvist, C., Frisén, L., & Lichtenstein, P. (2017). Increased Risk for Substance Use-Related Problems in Autism Spectrum Disorders: A Population-Based Cohort Study. Journal of Autism and Developmental Disorders, 47(1), 80–89. https://doi.org/10.1007/s10803-016-2914-2
(3) Arnevik, E. A., & Helverschou, S. B. (2016). Autism spectrum disorder and co-occurring substance use disorder - A systematic review. In Substance Abuse: Research and Treatment (Vol. 10, pp. 69–75). Libertas Academica Ltd. https://doi.org/10.4137/SART.S39921
(4) Pingault, J. B., Rijsdijk, F., Schoeler, T., Choi, S. W., Selzam, S., Krapohl, E., O’Reilly, P. F., & Dudbridge, F. (2021). Genetic sensitivity analysis: Adjusting for genetic confounding in epidemiological associations. PLOS Genetics, 17(6), e1009590. https://doi.org/10.1371/JOURNAL.PGEN.1009590
(5) Schumann, G., Coin, L. J., Lourdusamy, A., Charoen, P., Berger, K. H., Stacey, D., Desrivières, S., Aliev, F. A., Khan, A. A., Amin, N., Aulchenko, Y. S., Bakalkin, G., Bakker, S. J., Balkau, B., Beulens, J. W., Bilbao, A., de Boer, R. A., Beury, D., Bots, M. L., … Elliott, P. (2011). Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7119–7124. https://doi.org/10.1073/PNAS.1017288108
B4190 - Social behaviour and communication in context A multivariate genomic study of precursors and later-life outcomes - 21/11/2022
Background
Mastering motor milestones and social personal skills may lead to a developmental transition that initiates a cascade of developmental changes, including social interaction and language learning(1). For example, the onset of walking(1,2) and sitting skills(3) but also social-personal skills can predict children's vocabulary size, which may potentially affect literacy-related abilities in later life. Similarly, early abilities to distinguish prosody and rhythm may affect children’s progress in learning language and (social) communication. For example, musical rhythmicity is strongly linked to cognition due to the synchronization of the partner's language expression in social communication(4).
Various studies have shown the genetic overlap between interpersonal milestone development and neurodevelopmental disorders. For example, individuals diagnosed with Autism Spectrum Disorder (ASD) show delayed development of cognitive and social functioning and, therefore, may reach early developmental milestones later (smiling, walking, spoon feeding themselves, crawling) or not at all(5).
This project will use data from ALSPAC and other large cohorts to investigate the genetic architecture of early social/communicative/language abilities as well as social /social communication abilities during the life course within large consortia (e.g. meta-Genome Wide Association Analyses (GWAS) within the EAGLE consortium) including in-depth structural models of genetic factors. The study will biologically annotate the genetic architecture of early social/communicative abilities as well as social abilities through genetic enrichment and variance partitioning analyses. Once social behaviour has been modelled genetically, we will derive genetic tools to identify genetic overlap with neuro-developmental disorders and other health-related, educational and (social) behavioural outcomes in later life, as well as brain-related encodings (e.g. brain structure and function). The project will finally assess evidence for correlation and causal mechanisms linking precursors of social/communicative abilities (e.g. musicality, motor behaviour and temperament) to social performance and, in turn, social behaviour and social communication skills to later-life outcomes (e.g. health, education, behaviour).
1. Walle, E. A. Infant Social Development across the Transition from Crawling to Walking. Front. Psychol. 7, (2016).
2. Walle, E. A. & Campos, J. J. Infant language development is related to the acquisition of walking. Dev. Psychol. 50, 336–348 (2014).
3. Libertus, K. & Violi, D. A. Sit to Talk: Relation between Motor Skills and Language Development in Infancy. Front. Psychol. 7, (2016).
4. Ravignani, A., Honing, H. & Kotz, S. A. Editorial: The Evolution of Rhythm Cognition: Timing in Music and Speech. Front. Hum. Neurosci. 11, 303 (2017).
5. Kuo, S. S. et al. Developmental Variability in Autism Across 17 000 Autistic Individuals and 4000 Siblings Without an Autism Diagnosis: Comparisons by Cohort, Intellectual Disability, Genetic Etiology, and Age at Diagnosis. JAMA Pediatr. 176, 915–923 (2022).
B4195 - What makes clocks tick Mapping determinants of epigenetic age acceleration in early life - 15/11/2022
DNA methylation, the binding of a methyl-group to the DNA structure, can affect gene transcription and is related to aging. So strongly, in fact, that DNA methylation at specific sites (i.e. ‘CpGs’) can be used to estimate a persons’ age through the use of so-called ‘epigenetic clocks’. Not only do the age estimates produced by epigenetic clocks relate highly to chronological age, but the extent to which they deviate from chronological age is an important predictor of health: in adults, epigenetic age acceleration (i.e. being epigenetically older than one’s age) relates to greater disease risk and mortality, whereas conversely, deceleration relates to better health and longevity.
Research from our group suggests that an individual’s epigenetic age acceleration might be determined early on. We brought together the world’s largest developmental datasets with repeated epigenetic assessments to map how DNA methylation patterns change over the first two decades of life. We found that sites that make up epigenetic clocks already show substantial differences between individuals in early life, sometimes even from birth. This raises the possibility that longevity differences apparent in old age may already be influenced by factors occurring at a young age, opening new opportunities for early detection and intervention.
Here, we aim to identify the early origins of epigenetic aging, by examining the contribution of genetic and environmental influences, beginning in pregnancy. To do so, we use individual-level DNA methylation patterns of change at clock CpGs, already created. In addition, we will study early outcomes of inter-individual variation in early epigenetic age acceleration at the molecular and system-level.
B4187 - Inter-generational transmission of intimate partner violence and abuse IPVA influence of IPVA measures patterns and timing - 08/11/2022
Around one-quarter of young people in the UK report intimate partner violence and abuse (IPVA, that is, physical or sexual violence, or emotional abuse) among their parents by age 16. Research in US student samples suggests that for these young people, they are more likely to be victimised in their own intimate relationships as adolescents and young adults, this association my vary according to the timing of exposure to parental IPVA, and may be even higher for those with other adverse childhood experiences, such as maltreatment or parental mental illness. However, this has rarely been studied in a general population sample, or in the UK. Further, little is known about the burden
of continued IPVA over the life-course on later health, that is, witnessing IPVA among parents to then experiencing IPVA in one’s own relationship. However, IPVA among parents does not guarantee future IPVA, and many go on to not to experience this in their own intimate relationships. Understanding what factors (e.g. parent-child relationships, school, peers) help to break the cycle of intimate partner violence, can inform policies and interventions to prevent further violence and improve quality of life in these families.
B4194 - Genetic Determinants of Longitudinal Changes in Anthropometric Traits - 09/11/2022
This project aims to identify and characterize the contribution of genetic variation to growth-related traits. One part of this project will be conducted in collaboration with international consortia to identify genetic variants associated with height and body mass index (BMI) variation across childhood. The other part of the project will focus on genetic variants already associated with adult traits (height and BMI) and will characterise the critical time periods in childhood development when these variants start and stop to exert their effects.
B4021 - longitudinal modeling of high-dimensional molecular measurements in birth cohort studies - 07/11/2022
Our group at the Singapore Institute for Clinical Sciences and the University of Manchester have received funding from the Wellcome Trust to investigate the machine learning modelling techniques for high-dimensional measurements from population studies. Recently, high-throughput 'omics technologies have allowed us to collect large numbers of molecular measurements from a single sample. Analysing these large datasets poses a problem, because existing techniques do not allow us to analyse all measurements jointly as outcomes. We will develop a statistical technique for jointly analysing large numbers of molecular measurements, using recent advances in statistical inference, as well as applying prior knowledge to reduce the number of relationships between measurements that needs to be explored. Additionally, we will develop a method for designing longitudinal studies to gain optimal information about these high-dimensional outcomes. The benefits of our approach will be two-fold: First, in allowing us to gain additional information about the relationships between longitudinal measurements, and second in improving the design of future studies, which will lead to time and cost savings.
B4178 - Validation of selected candidate blood metabolites biomarkers for age at menopause - 07/11/2022
Female reproductive longevity, controlled by the timing of menarche and menopause, can vary greatly depending on genetics, lifestyle, and environmental exposures. While variations in age at menarche (AAM) and age at natural menopause (ANM) have a complex multi-factorial aetiology, the biological mechanisms underlying these variations are still not fully understood. Identifying biomarkers allows for a better understanding of the pathophysiology underpinning variations in AAM and ANM and their interconnection, while the same molecules could represent potential targets to pharmacologically modify timing of these events. High-throughput metabolomics studies have led to the discovery of a number of candidate biomarkers for a variety of traits. However, simultaneous measurement of hundreds of circulating metabolites in case-control studies is cost prohibitive and subject to confounding and reverse causation. Large genome-wide association studies (GWAS) have become available for both metabolites and AAM and ANM, advancing our knowledge on the genetic determinants of these traits. Mendelian randomisation (MR) is an established method in genetic epidemiology that explores whether a modifiable exposure is causally linked to an outcome by using genetic variants for this exposure as instrumental variables. The MR design can avoid potential bias from confounding that are typical in conventional observational studies by taking advantage of the fact that inherent genetic variants are not susceptible to environmental risk factors and reverse causation. In a setting known as two-sample MR, GWAS data for an exposure and an outcome measured in independent populations can be used to test causality of risk factors on complex health outcomes.
By employing two-sample MR, we screened hundreds of previously measured circulating metabolites for causal association with AAM and ANM. Genetic variants associated with each metabolite were extracted from four large metabolomic GWAS and effects of these variants on AAM and ANM were retrieved from the largest GWAS conducted for AAM (N = 329,345), and ANM (N = 200,000). We discovered 12 blood metabolites with evidence of a causal relationship with the AAM and 114 metabolites associated with ANM. Using multivariable MR, we found that the majority of these metabolites affect the timing of AAM or ANM regardless of body mass index (BMI). These molecules cluster in specific pathways, such as that of amino acid synthesis and glycerophosphocholine synthesis. We identified two of the candidate metabolites for AAM as significantly associated with ANM in ALSPAC participants (data requested as part of a separate project [B3667], aiming to predict AAM using a combination of genetic and non-genetic risk factors). Specifically we found an association between higher phosphatidylcholine levels and a later onset of AAM, and a link between lower isoleucine levels and an earlier onset of AAM, and the magnitude of the effects were comparable with those of the MR study. In this proposal, we request data on metabolites levels and AAM of ALSPAC mothers, in order to seek validation for a portion of the 114 candidate metabolites for ANM prioritized by our MR study, which have been measured in ALSPAC. This validation will provide further support to our MR findings, suggesting a causal role of the above metabolites in ANM.
B4174 - Better understanding the inter-generational transmission of intimate partner violence and abuse - 07/11/2022
Around one-quarter of young people in the UK report intimate partner violence and abuse (IPVA, that is, physical or sexual violence, or emotional abuse) among their parents by age 16. Research in US student samples suggests that for these young people, they are more likely to be victimised in their own intimate relationships as adolescents and young adults, this association my vary according to the timing of exposure to parental IPVA, and may be even higher for those with other adverse childhood experiences, such as maltreatment or parental mental illness. However, this has rarely been studied in a general population sample, or in the UK. Further, little is known about the burden of continued IPVA over the life-course on later health, that is, witnessing IPVA among parents to then experiencing IPVA in one’s own relationship. However, IPVA among parents does not guarantee future IPVA, and many go on to not to experience this in their own intimate relationships. Understanding what factors (e.g. parent-child relationships, school, peers) help to break the cycle of intimate partner violence, can inform policies and interventions to prevent further violence and improve quality of life in these families.
B4188 - Parental Type 2 Diabetes and Cardiovascular disease polygenic risk scores by offspring birthweight and placental weight - 14/11/2022
Birth weight (BW) and placental weight (PW) have been associated with adult health outcomes, and a genetic component for this relationship has been established. Similar associations between offspring BW and PW and parental health have been found in observational studies. We aim to investigate the association of parental diabetes and cardiovascular disease risk variants with offspring BW and PW.
B4182 - Neurodevelopmental characteristics of children with genetic risk for epilepsy - 31/10/2022
Epilepsy is the most common primary neurological disorder worldwide, with 10% of people experiencing a seizure during their life. Seizures often occur in combination with other neurological or behavioural traits indicating altered brain development. Seizures might also themselves negatively impact the neurocognitive development in early life. Understanding the links between epilepsy and other neurodevelopmental and neurological conditions is key to understanding the mechanism and impact of the disease. Large genome-wide association studies of epilepsy have found specific genes that are linked to brain function and might therefore explain the vulnerability of specific brain circuits in people experiencing seizures. It is not clear though how these genetic predispositions to epilepsy would affect other brain properties, for instance neurocognitive development. Therefore, we propose to investigate the molecular, neurodevelopmental and cognitive outcomes of having a genetic predisposition for epilepsy in the ALSPAC children.
B4185 - To investigate pathways relating to environmental risk factors immune markers and mental health outcomes in early adulthood - 31/10/2022
We and others have identified numerous factors that influence mental health in young adults and early adulthood. These include obstetric complications, adversity, cannabis use, population density, immigrant status (PMID: 29352556, 12091183, 31563981) and most recently exposure to COVID (PMID: 35987197). Additionally, in the ALSPAC cohort, we recently identified that suicidal ideation at age 17 is associated with 7-fold increased odds of psychotic disorder, and with depressive disorder and generalised anxiety disorder at age 24. Indeed, over 40% of those with psychotic disorder in early adulthood had experienced this symptom in late adolescence (Mongan et al, 2022, unpublished).
We and others have also identified evidence for inflammatory marker dysregulation both preceding and in association with psychiatric disorders including psychosis, depression and recently, long COVID (PMID: 36085284 , 35472304). Dysregulation of acute inflammatory markers [such as Interleukin (IL)-6 and C-Reactive Protein] and complement proteins has been reported prior to and in association with these outcomes (PMID: 25133871, PMID: 32857162). Using ALSPAC data we identified for the first time the cross-sectional association of suPAR (soluble urokinase plasminogen activator receptor- an established marker of chronic inflammation) and IL-6 (an established marker of primarily acute inflammation) with psychotic disorder in young adults (Mongan et al 2022, under review). We previously found an inverse association between the antiinflammatory marker n-3 fatty acid docosahexaenoic acid (DHA) at age 17 and psychotic disorder at age 24 in the ALSPAC cohort (PMID 34059620). Using ALSPAC data we have also shown for the first time that elevated suPAR is associated cross-sectionally with cannabis exposure, itself a marker for mental illhealth (Power et al 2022 (under review)). We now seek to expand our knowledge to mental health outcomes in early adulthood (at age 24 and also at age 30 (when available)). We wish to examine not only associations between risk factors and inflammation in relation to clinical thresholds of psychiatric disorders, but also in relation to specific symptoms and symptom severity.
We hypothesise that exposure to environmental risk factors and early-life adversity is associated with chronic inflammatory dysregulation, in line with recent evidence (PMID: 31682707, 26033244, 34990745). We also hypothesise that inflammatory dysregulation will be more common in those who go on to report mental disorders in adulthood (PMID: 25133871, PMID: 32857162). Crucially, we hypothesise that inflammatory dysregulation mediates the relationship between environmental exposures and adult mental disorders, which could provide evidence for a biological mechanism by which environmental exposures influences the risk of adult mental disorder. Alternatively, environmental exposures and biological risk factors may operate independently, but have a cumulative effect on the risk of mental disorders.
We propose to investigate this using a combination of existing ALSPAC data, and new data derived from assays undertaken by us which assessed levels of the robust marker of chronic inflammation, suPAR, in age 24 plasma samples donated by ALSPAC participants.
Only data from B4168 will be used.