Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B4169 - Predictors of blood mercury levels during pregnancy - 24/10/2022

B number: 
B4169
Principal applicant name: 
Sarah Lewis | Population Health Sciences, IEU (United Kingdom)
Co-applicants: 
Kyle Dack, Caroline Taylor, Dheeraj Rai
Title of project: 
Predictors of blood mercury levels during pregnancy
Proposal summary: 

This project aims to improve our understanding of which factors are predictive of mercury levels in pregnant women. Many factors have been reported in isolation, but little work has previously been done to compare them and identify their relative importance. Fish consumption is likely to be a primary source, but there may be a role of social factors (eg job) and genetic makeup.

Impact of research: 
The results would be novel, as mercury predictors have not been compared in this way before. It will improve our understanding of their relative importance.
Date proposal received: 
Wednesday, 12 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4173 - From Suicide Ideation to Suicide Attempt Clarifying the Role of Painful and Provocative Events - 24/10/2022

B number: 
B4173
Principal applicant name: 
Alexis Edwards | Virginia Commonwealth University (United States)
Co-applicants: 
Mallory Stephenson
Title of project: 
From Suicide Ideation to Suicide Attempt: Clarifying the Role of Painful and Provocative Events
Proposal summary: 

Several leading theories of suicide propose that capability for suicide is acquired across development, in part through exposure to physically painful and/or fear-inducing experiences, collectively referred to as painful and provocative events (PPEs). However, studies investigating the association between exposure to PPEs and risk for suicide attempt are usually cross-sectional (the exposure and outcome are measured at the same time) and do not employ a genetically-informed approach. In this project, we will use data from the ALSPAC study to further characterize the association between PPE exposure and risk for suicide attempt. First, we will test whether the association between genetic liability and risk for suicide attempt is mediated by impulsivity and exposure to PPEs, such as aches and pains, injuries, accidents, and traumatic events. Second, we will investigate whether the magnitude of the association between PPE exposure and risk for suicide attempt in adolescence varies based on parenting behaviors, as positive parenting behaviors may buffer risk associated with exposure to PPEs.

Impact of research: 
These analyses will clarify the relationships between painful and provocative events, genetic risk for suicide attempt, impulsivity, parenting, and suicidal behavior, while also considering differences in the development of suicide attempt based on biological sex. We anticipate that our findings will yield insight into the predictive utility of ideation-to-action theories of suicide and highlight relevant risk factors for the transition from suicide ideation to attempt in adolescence.
Date proposal received: 
Tuesday, 18 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Social Science, Mental health, Biological samples -e.g. blood, cell lines, saliva, etc., Genetics, Injury (including accidents), Parenting, Sex differences

B4177 - CAMCOG Data processing - 24/10/2022

B number: 
B4177
Principal applicant name: 
Ian Penton-Voak | University of Bristol, UK (United Kingdom)
Co-applicants: 
Rumeysa Kuruoglu, Kate Northstone
Title of project: 
CAMCOG: Data processing
Proposal summary: 

This project will process the data that ALSPAC has collected from participants using CAMCOG (cogntive tests)

Impact of research: 
TBC
Date proposal received: 
Friday, 21 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Epidemiology, Cognitive impairment, Cognition - cognitive function

B4168 - Investigating pathways relating to environmental risk factors immune markers and mental health outcomes in early adulthood - 27/10/2022

B number: 
B4168
Principal applicant name: 
David Cotter | Royal College of Surgeons in Ireland (Ireland)
Co-applicants: 
Professor Stan Zammit, Professor Mary Cannon, Dr Colm Healy, Dr David Mongan, Dr Subash Raj Susai, Dr Melanie Focking, Jennifer Murphy, Jonah Byrne
Title of project: 
Investigating pathways relating to environmental risk factors, immune markers and mental health outcomes in early adulthood.
Proposal summary: 

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 anti-inflammatory 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 ill-health (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.

Impact of research: 
This research will allow us to further elucidate the relationship between risk factors for mental disorders, biological markers of inflammation, and psychiatric and functional outcomes
Date proposal received: 
Wednesday, 12 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4171 - Biopsychosocial stress in pregnancy birth outcomes motor mental health trajectories in childhood - 27/10/2022

B number: 
B4171
Principal applicant name: 
Mary Clarke | Royal College of Surgeons Ireland (RCSI) (Ireland)
Co-applicants: 
Miss Emma Butler, Dr Linda O Keeffe, Dr Michelle Spirtos
Title of project: 
Biopsychosocial stress in pregnancy, birth outcomes & motor & mental health trajectories in childhood
Proposal summary: 

Stress in pregnancy has been linked with adverse cognitive, motor and mental health outcomes in the offspring. In previous research studies stress has been represented by major life events, maternal mental health, economic hardship or stress biomarkers. Due to the wide variability in how stress has been quantified to date we do not know what types of stress or how much stress matters for whom and for which specific developmental outcomes. In addition, far less research has focused on sensorimotor outcomes despite the fact that the central nervous system is most vulnerable as it develops earliest in gestation and for the longest duration in-utero. Furthermore, adequate sensorimotor development may be a protective factor for later mental health. This study aims to quantify stress across biopsychosocial domains both independently and cumulatively, examining its influence on specific adverse birth outcomes (e.g. gestational age, birthweight, mode of delivery and neonatal complications), fine and gross motor trajectories in early childhood and mental health trajectories in middle/late childhood. Moderators such as infant sex, post-natal environment and activity engagement will also be considered.

Impact of research: 
Hopefully to identify which types of women and in turn which types of children are most at-risk of adverse development outcomes not just categorised as a binary clinical need but across the spectrum of outcomes. This may illuminate new factors which need to be considered in practice to quantify risk e.g. giving consideration to poly social risk as well as polygenic risk and to allow intervention to be provided to promote optimum development rather than waiting to intervene once a clinical threshold has been reached.
Date proposal received: 
Friday, 14 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Sex differences

B4170 - Assessing the impact of missing data in auxiliary variables on multiple imputation estimates - 02/11/2022

B number: 
B4170
Principal applicant name: 
Paul Madley-Dowd | University of Bristol (United Kingdom)
Co-applicants: 
Professor Kate Tilling, Dr Jon Heron, Dr Rachael Hughes, Elinor Curnow
Title of project: 
Assessing the impact of missing data in auxiliary variables on multiple imputation estimates
Proposal summary: 

Data are frequently missing in observational cohorts which can lead to bias in estimates of effect sizes between exposure and outcome. We use a method called multiple imputation to try to correct for this. Auxiliary methods are often essential for removing bias in multiple imputation analyses, but are frequently missing themselves. We aim to apply simulations and an empirical example (using ALSPAC data) to assess how missing data in auxiliary variables can impact multiple imputation analyses.

Impact of research: 
We aim to improve current practice of the implementation of multiple imputation.
Date proposal received: 
Friday, 14 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Statistics/methodology, Cognitive impairment, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B4172 - Understanding pathways from environmental risk to internalising problems for autistic young people - 21/11/2022

B number: 
B4172
Principal applicant name: 
Will Mandy | UCL (UK)
Co-applicants: 
Prof Eirini Flouri, Dr Emily Midouhas, Dr Kate Cooper
Title of project: 
Understanding pathways from environmental risk to internalising problems for autistic young people
Proposal summary: 

This project will investigate the role of the social and physical environment in the development of internalising problems (i.e., anxiety and depression) in autistic young people (AYP), thereby contributing new insights to inform prevention and treatment. Internalising problems are common in autistic people, with a lifetime prevalence around four times that of non-autistic people. They typically arise by adolescence, persist across the lifespan and have substantial negative effects on wellbeing, functioning, physical health and mortality. The need for work that informs care for internalising problems has been highlighted by the autism community as their top priority for autism research. This reflects the fact that evidence-based interventions for autistic internalising problems are lacking because, currently, our understanding of how and why these difficulties develop and persist is limited. In particular, we lack understanding of how features of the social and physical environment influence the development of internalising problems of AYP.

Across the whole project, we take an ecological approach to understanding the development of internalizing problems in AYP. We seek to understand the development of mental health problems by modelling the dynamic interplay of environmental and personal factors and elucidating how diverse factors at different levels operate over time.

By enhancing understanding of autistic mental health, the study will help improve the wellbeing and life chances of autistic people by informing the development of interventions to treat and prevent their mental health problems. Our focus on environmental risk is especially likely to yield practical results, as it promises the identification of modifiable risk factors (e.g., parenting, peer victimisation, neighbourhood built environment) as putative targets for intervention.

Impact of research: 
By enhancing understanding of autistic mental health, the study will help improve the wellbeing and life chances of autistic people by informing the development of interventions to treat and prevent their mental health problems. Our focus on environmental risk is especially likely to yield practical results, as it promises the identification of modifiable risk factors (e.g., parenting, peer victimisation, neighbourhood built environment) as putative targets for intervention.
Date proposal received: 
Monday, 17 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Developmental disorders - autism, Statistical methods, Childhood - childcare, childhood adversity

B4175 - Exploring bidirectional associations between menstrual symptoms and socioeconomic disadvantage - 07/11/2022

B number: 
B4175
Principal applicant name: 
Laura Howe | MRC Integrative Epidemiology Unit at the University of Bristol (United Kingdom)
Co-applicants: 
Gemma Sawyer, Gemma Sharp
Title of project: 
Exploring bidirectional associations between menstrual symptoms and socioeconomic disadvantage.
Proposal summary: 

Problematic menstrual symptoms, such as pain, heavy bleeding, and irregular cycles, impact a high proportion of women and people who menstruate and are associated with multiple adverse physical and mental health outcomes, as well as reduced attendance and productivity at school/work. Despite this, little research has sought to identify the causes and risk factors associated with such menstrual symptoms. Socioeconomic disadvantage is one factor that has been associated with worse menstrual symptoms; however, the current evidence is mixed and unable to understand causality. It is possible that socioeconomic position (SEP) causally impacts menstrual symptoms due to early life stressors and associated lifestyle factors adversely impacting the development of the brain, the nervous system, and hormone production systems. Additionally, menstrual symptoms could negatively impact SEP through their impacts on school and work thus restricting the ability of women suffering with such symptoms to reach their fully academic and career potential. Therefore, this project aims to understand the causal, bidirectional relationship between SEP and menstrual symptoms by combining observational and genetic methods in multiple UK-based cohorts. Robust evidence that SEP and menstrual symptoms are causally related may support the need for additional support or treatment for individuals from disadvantaged backgrounds and/or provide rationale for improving school and work environments to enable women to better manage problematic menstrual symptoms.

Impact of research: 
This research will improve understanding of the prevalence and patterns of problematic menstrual symptoms for which there is limited research. It will also increase understanding of the complex relationship between menstrual symptoms and socioeconomic disadvantage, which could possibly contribute to building rationale for providing additional support to disadvantaged women and improving school and work environments to help women better manage problematic menstrual symptoms.
Date proposal received: 
Wednesday, 19 October, 2022
Date proposal approved: 
Monday, 24 October, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc.

B4167 - Long-term Impacts of Childhood Head Injuries and Conduct Problems on Executive Function - 21/10/2022

B number: 
B4167
Principal applicant name: 
Valerie Brandt | University of Southampton
Co-applicants: 
Hannah Carr, Dr. Yuning Zhang
Title of project: 
Long-term Impacts of Childhood Head Injuries and Conduct Problems on Executive Function
Proposal summary: 

There appears to be a sensitive period from ages 7 to 11 whereby conduct problems and head injuries promote one another. Individually, both have been associated with poor executive functioning such as disinhibition, poor working memory, and deficits in emotion recognition. However, what is not yet known is how this bidirectional association between ages 7 to 11 may affect executive function in adulthood. To address this gap in the literature, we plan to estimate how executive function at age 24 may be predicted by childhood head injuries and conduct problems from ages 7 to 11.

Impact of research: 
Our research will provide novel insight into the long-term outcomes of childhood conduct problems and head injuries. If this study highlights executive dysfunction into adulthood, it will further stress the need for future research into appropriate treatment and preventions for both conduct problems and head injuries between ages 7 and 11.
Date proposal received: 
Tuesday, 11 October, 2022
Date proposal approved: 
Friday, 21 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function

B4161 - Environmental and socioeconomic influences on pubertal development an international comparative study - 18/10/2022

B number: 
B4161
Principal applicant name: 
Ahmed Elhakeem | MRC IEU
Co-applicants: 
Ana Gonçalves Soares
Title of project: 
Environmental and socioeconomic influences on pubertal development: an international comparative study
Proposal summary: 

Puberty and adolescence is an important period in human development characterized by rapid transformations in anatomy, physiology, and behaviour, and the establishment of social and economic resources to maintain health and wellbeing across the life course. Despite the importance of puberty, little is known on the patterns of various developmental changes during puberty. Early life environmental exposures and socioeconomic position are thought to influence later health but whether they influence pubertal development is unclear. This study will describe the timing of different markers of pubertal development in 3 cohorts from the UK, USA, and Denmark, and examine early life environmental and socioeconomic influence on the timing of puberty.

Impact of research: 
The study will provide new evidence on the patterns of pubertal growth and development and their early life influences. this will be of interest to families, clinicians, researchers and policy makers. The analysis code will be made available which will help researchers to build skills in advanced methodological approaches to analysis of repeated measures
Date proposal received: 
Wednesday, 12 October, 2022
Date proposal approved: 
Tuesday, 18 October, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Development

B4163 - Longitudinal Blood Pressure GWAS - 18/10/2022

B number: 
B4163
Principal applicant name: 
Kari E. North | University of North Carolina Chapel Hill (USA)
Co-applicants: 
Dr. Samson Okello, Assist. Prof. Heather Highland, Misa Graff
Title of project: 
Longitudinal Blood Pressure GWAS
Proposal summary: 

Blood pressure increases with aging and individuals with elevated blood pressure during adolescence and early adulthood are more likely to have hypertension and heart disease later in life. Knowledge of genetic factors associated with blood pressure during adolescence and early adulthood may help in the development of strategies to control blood pressure and prevent heart disease.

Impact of research: 
We anticipate insights into mechanistic pathways leading to hypertension, identifying novel targets for early prevention and pharmaceutical intervention to reduce CVD-related morbidity. By addressing BP in a life course approach, our work will contribute to the understanding of CVD risk in early life.
Date proposal received: 
Friday, 14 October, 2022
Date proposal approved: 
Tuesday, 18 October, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Hypertension, GWAS, Blood pressure

B4166 - GWAS of longitudinal subtypes of atopic dermatitis - 19/10/2022

B number: 
B4166
Principal applicant name: 
Ashley Budu-Aggrey | MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School (United Kingdom)
Co-applicants: 
Dr Lavinia Paternoster, Raquel Granell, Dr Sadia Haider
Title of project: 
GWAS of longitudinal subtypes of atopic dermatitis
Proposal summary: 

We plan to identify genetic markers across the genome for subtypes of childhood eczema across the course of disease. These phenotypes include "no eczema", early transient eczema", "late-onset eczema", "intermittent eczema" and "persistent eczema", which have been generated using information from 5 points in times throughout childhood. These time points include age 6 months to 1 year; 2-3 years; 4-5 years; 8-10 years and 14-18 years of age. This study will help us understand the genetic and environmental factors that may differ between different disease subtypes, and will help inform the definition of eczema and how it is treated.

Impact of research: 
This study will help us understand the genetic and environmental factors that may differ between different disease subtypes, and will help inform the definition of eczema and how it is treated.
Date proposal received: 
Friday, 7 October, 2022
Date proposal approved: 
Tuesday, 18 October, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Eczema, GWAS, Genome wide association study

B4164 - The bidirectional relationships among physical activity sedentary behaviour weight status and depression - 19/10/2022

B number: 
B4164
Principal applicant name: 
Rodrigo Antunes Lima | Parc Sanitari Sant Joan de Déu (España)
Co-applicants: 
Josep Maria Haro, PhD, Albert Sanchez Niubo, Joan Domènech Abella, PhD, Elena Condominas
Title of project: 
The bidirectional relationships among physical activity, sedentary behaviour, weight status and depression
Proposal summary: 

This project will evaluate how physical activity, sedentary behaviour, obesity and depression influence one another during adolescence (age 12 to 18 years). We will use data from the ALSPAC study, which has been following these adolescents since their birth in 1991-1992. This project will support practitioners, researchers and policy makers in designing effective public health interventions that target the increasing rates of obesity, depression and physical inactivity by understanding the complexity of their relationships during adolescence.

Impact of research: 
This project will support researchers and practitioners in understanding the complex relationships among sedentary behaviour, physical activity, weight status and depression during adolescence and how these relationships develop over time. For example, this project might indicate that it might be more appropriate to focus on increasing physical activity level in early adolescence or to target adiposity in middle adolescence because of the strength of the relationships that might be observed. Therefore, providing support on the best interventional approaches to target low levels of physical activity and higher rates of obesity and depression in the adolescent population.
Date proposal received: 
Friday, 7 October, 2022
Date proposal approved: 
Tuesday, 18 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Obesity, Physical innactivity, Statistical methods, BMI, Physical - activity, fitness, function

B4165 - Association between SNPs in candidate genes for good motor skills and childrens motor coordination - 24/10/2022

B number: 
B4165
Principal applicant name: 
Hideki Moriyama | Kobe University (Japan)
Co-applicants: 
Mr. Shota Inoue
Title of project: 
Association between SNPs in candidate genes for “good motor skills” and children's motor coordination
Proposal summary: 

Physical abilities are complex traits that are influenced by both genetic and environmental factors. Genetic factors account for 20-80% of muscle strength, endurance capacity, speed, and flexibility. Physical abilities depend on motor coordination, which is defined as the dexterity to coordinate movements of multiple body parts. Well-developed coordination allows people to control their body parts in space and time quickly, efficiently, and accurately; so-called "good motor skills”. Motor coordination was commonly thought to be more influenced by environmental factors. However, recent twin studies have shown the heritability of motor coordination, suggesting the involvement of genetic factors in “good motor skills”.

Recently, we have demonstrated the heritability of “motor skills” by selective breeding in mice for good and poor coordination. Our comprehensive genomic and gene functional analyses in these mouse lines also identified candidate genes responsible for “good motor skills” in the cerebellum and cerebral cortex. The goal of this study is to determine whether the candidate genes for “good motor skills” identified by animal studies are involved in human motor coordination. To reach our goal, we investigated the association of SNPs in 11 candidate genes with children’s motor coordination using ALSPAC data.

Impact of research: 
The sports genomics approach has provided many insights into genomic associations of endurance- and power-based exercise performance. This research will lead to a better understanding of the relationship between motor coordination and genetic factors, opening up a new field of research for “good motor skills”.
Date proposal received: 
Friday, 7 October, 2022
Date proposal approved: 
Tuesday, 18 October, 2022
Keywords: 
Genetics, Developmental disorders - autism, DNA sequencing, GWAS, Development, Genetics, Genomics, Physical - activity, fitness, function

B4157 - Associations between polygenic risk scores reaction time variability and ADHD-traits during adolescence - 11/10/2022

B number: 
B4157
Principal applicant name: 
Christian Krog Tamnes | University of Oslo
Co-applicants: 
Ingrid Anna Ørstavik Dissen, Rosa Catherine Gillespie Cheesman, Dr., Alexandra Havdahl, Dr., Iroise Dumontheil, Dr.
Title of project: 
Associations between polygenic risk scores, reaction time variability and ADHD-traits during adolescence
Proposal summary: 

The current project is a student project that is linked to the already approved project: B3840 Developmental pathways to mental health problems. All needed data are available through B3840.

Attention deficit/hyperactivity-disorder (ADHD) is a highly heritable and heterogenous neurodevelopmental disorder associated with a range of cognitive deficits and functional outcomes. The complex pathways in which genetic risk gives rise to traits associated with ADHD remains to be specified. One cognitive phenotype associated with ADHD is Intraindividual Variability (IIV), usually measured as Reaction Time Variability (RTV). How RTV relates to behavioural symptoms of ADHD, and whether it constitutes a specific marker of ADHD or represents a marker of psychopathology in general, is currently debated. A deeper understanding of how genetic risk for ADHD relates to RTV and how RTV in turn relates to ADHD symptoms may have implications for understanding the links between genetic risk, cognition, and behavioural manifestations of ADHD.

Impact of research: 
Date proposal received: 
Friday, 30 September, 2022
Date proposal approved: 
Tuesday, 11 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, ADHD, Polygenic scores Behavioural task, Cognition - cognitive function

B4159 - Genome-wide association study GWAS of blood pressure in adults - 11/10/2022

B number: 
B4159
Principal applicant name: 
Qian Yang | University of Bristol
Co-applicants: 
Prof Deborah A Lawlor, Prof Nicholas J Timpson
Title of project: 
Genome-wide association study (GWAS) of blood pressure in adults
Proposal summary: 

The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium invites ALSPAC and Bristol researchers to take part in a large GWAS of blood pressure traits, which include systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP, i.e. SBP-DBP). The main aims of CHARGE's GWAS are to (1) identify novel loci for BP traits separately by sex; (2) identify gene-sleep interaction effects on BP traits by sex. These analyses will follow the most recent analysis plan (currently 'Phase II analysis plan for sleep and blood pressure' version 4.3) provided by CHARGE. Only summary statistics will be shared with CHARGE. Based on the final GWAS results, subsequent analyses (e.g. Mendelian randomization) would be conducted by CHARGE based on the summary statistics.

Impact of research: 
This study will help identify novel genetic variants involved in BP traits and genetic variants affect these traits taking into account potential interaction with a lifestyle factor.
Date proposal received: 
Monday, 3 October, 2022
Date proposal approved: 
Tuesday, 11 October, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Hypertension, GWAS, Blood pressure

B4160 - Novel implementation of vaccinations against adult respiratory infection and respiratory pathogen surveillance - 04/11/2022

B number: 
B4160
Principal applicant name: 
Catherine Hyams | University of Bristol
Co-applicants: 
Title of project: 
Novel implementation of vaccinations against adult respiratory infection and respiratory pathogen surveillance
Proposal summary: 

Vaccination is currently underutilised in adults, despite the potential for this public health intervention to improve patient outcomes, and reduce healthcare usage and expense. Pre-licensure randomised controlled trials demonstrate vaccine safety and efficacy, but fail to evaluate the impact of these interventions in real-world settings, providing limited insight into outcomes for healthcare systems. Current post-implementation surveillance and safety studies lack detailed clinical outcomes and are limited by methodological constraints. There is therefore an urgent need to undertake well-conducted post-licensure pre-rollout (i.e. vaccine incorporation into national programmes) interventional implementation studies to provide such evidence.

This fellowship will aim to develop the methodology used within this field and undertake research that provides critical evidence for national and international public health decision making. Initially, I aim to undertake this research through an exemplar study of PCV20 (20-valent pneumococcal conjugate vaccine), which may extend into a post-implementation effectiveness study if PCV20 is implemented nationally. This would then provide a pre-existing platform to study RSV or novel influenza vaccine effectiveness.

Impact of research: 
The research proposed in this fellowship aims to improve understanding of human infectious disease and translating these insights into health benefits, thereby ensuring that the UK has the infrastructure, skills and expertise it needs. As such, it falls within the scope of the Infection and Immunity Board. Specific areas of strategic focus covered include: Global Health; Preparedness; Immunity and Infection throughout life; Chronic infection, comorbidity, immunomodulation.
Date proposal received: 
Tuesday, 4 October, 2022
Date proposal approved: 
Tuesday, 11 October, 2022
Keywords: 
Health Economics, Infection, Qualitative study, Cohort studies - attrition, bias, participant engagement, ethics

B4150 - A Network Approach to Understanding Co-Occurring Mental Health Conditions in People with Autism and High Autistic Traits - 03/10/2022

B number: 
B4150
Principal applicant name: 
Matthew Hollocks | King's College London
Co-applicants: 
Dr Anat Zaidman-Zait, Prof Will Mandy
Title of project: 
A Network Approach to Understanding Co-Occurring Mental Health Conditions in People with Autism and High Autistic Traits
Proposal summary: 

Autism spectrum disorder is a neurodevelopmental condition characterised by difficulties with reciprocal social communication, restricted interests, repetitive behaviours, and sensory difficulties. In addition to these core features autistic people are at extremely high risk of developing additional mental health difficulties. For example, between 40% to 78% of children with autism have at least one anxiety disorder, almost four times the rate observed in children without the diagnosis. In addition, rates of depression and ADHD are extremely high. Adding to this complex picture is the fact that an autistic person will often experience more than one of these additional diagnoses. Current statistical approaches to the study of the co-occurrence of mental health conditions in autism fail to consider of important associations at a symptom level both within and between conditions, potentially preventing vital insights into key problem areas which could be targeted by interventions. To address this, we plan to apply an alternative and novel approach (Network analysis) to understanding the underlying structure of co-occurring conditions in this highly complex and heterogeneous population.

Impact of research: 
The main outcome of this research will be a novel understanding of the nature of co-occurring mental health conditions in autism. Our approach will allow us to identify key symptoms or clusters of symptoms which will guide future research on the assessment, prevention and treatment of the mental health difficulties experienced by autistic people.
Date proposal received: 
Wednesday, 28 September, 2022
Date proposal approved: 
Monday, 3 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity, Development, Psychology - personality, Statistical methods

B4154 - The role of genetics in food allergy - 03/10/2022

B number: 
B4154
Principal applicant name: 
Annette Peters | Helmholtz Munich and Ludwig Maximilian University of Munich (Germany)
Co-applicants: 
Lisa Maier
Title of project: 
The role of genetics in food allergy
Proposal summary: 

The prevalence of food allergies has steadily increased in recent decades. This highlights the contribution of environmental and lifestyle factors, which act on the background of individual genetic susceptibility to shape the responsiveness of the immune system to allergenic triggers. A few genetic regions associated with food allergy have been identified but the number of genome-wide association studies (GWAS) on food allergy to date is limited and often restricted to one specific food allergen. Therefore, we aim to conduct a large-scale meta-analysis of GWAS on food allergies.

Impact of research: 
This project aims in particular to identify new risk loci for food allergy, as only a few genes have been identified so far in studies with small sample sizes. Conducting a GWAS meta-analysis on food allergy will expand and improve the understanding of genetic mechanisms of food allergies, which is an essential prerequisite for developing hypothesis-generating approaches to food allergy prevention and therapy.
Date proposal received: 
Thursday, 22 September, 2022
Date proposal approved: 
Monday, 3 October, 2022
Keywords: 
Genetics, Allergy, GWAS, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Cohort studies - attrition, bias, participant engagement, ethics, Genetic epidemiology, Genetics, Genome wide association study, Immunity, Statistical methods

B4158 - An investigation of the developmental symptom course of chronic pain and mental health Using genetically informative and causal - 03/10/2022

B number: 
B4158
Principal applicant name: 
Ellen Thompson | KCL (United Kingdom)
Co-applicants: 
Title of project: 
An investigation of the developmental symptom course of chronic pain and mental health: Using genetically informative and causal
Proposal summary: 

Chronic pain impacts multiple aspects of the lives of people who experience it with up to 10% of young people experiencing chronic pain into early adulthood, including symptoms of musculoskeletal pain, recurrent abdominal pain, and headaches. Importantly, it is estimated that up to 72% of those who experience chronic pain also experience significant levels of depression and anxiety (also referred to as common mental health problems hereafter). Despite these shocking estimates, few studies have sought to understand the causes, mechanisms, and longitudinal relationship between symptoms of chronic pain and common mental health problems.

The overarching aim of this project is to investigate the direction of the relationship between chronic pain and common mental health across a developmental period, from childhood to young adulthood, and explore potential mechanisms which may elucidate individual differences in the development of symptoms. To do this I will apply advanced statistical methods to large, genetically informative, longitudinal population-based studies to test the relationship between chronic pain symptoms including headaches, backache, and abdominal pain and common mental health problems, including anxiety and depression. Findings will provide a deeper understanding into the causal relationship between symptoms of chronic pain and common mental health across a key developmental period.

Impact of research: 
During the course of my project, I will produce and disseminate academic papers. I will aim to publish, in an open-access form, in high impact journals such as Nature Human Behaviour, The British Journal of Psychiatry, Lancet Psychiatry and Journal of Child Psychology and Psychiatry, which will reach a broad audience. Furthermore, I will address academic and clinical audiences in national and international conferences and departmental seminars across the UK and internationally. Additionally, I will engage public audiences in dialogue about my research and foster public understanding of chronic pain in the development of mental health symptoms and their environmental and genetic underpinnings
Date proposal received: 
Monday, 3 October, 2022
Date proposal approved: 
Monday, 3 October, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Pain, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

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