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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B4077 - Using metabolomic data statistics and machine learning to predict severe COVID-19 and long COVID - 30/05/2022

B number: 
B4077
Principal applicant name: 
Milla Kibble | University of Bristol (United Kingdom)
Co-applicants: 
Dr Francisco Perez-Reche, Dr Joshua Bell, Prof. Nicholas Timpson
Title of project: 
Using metabolomic data, statistics and machine learning to predict severe COVID-19 and long COVID
Proposal summary: 

The central idea of the proposed research is to use metabolic biomarkers to predict the severity of COVID-19 and the likelihood of long COVID for individuals that have not necessarily been diagnosed with a pre-existing health condition. To this end, we will use pre-pandemic data from several cohort studies which, in addition to basic information on age, sex, ethnicity, etc, contain hundreds of metabolic biomarkers for thousands of individuals. To understand the link between these characteristics and the impact of COVID-19, we will use symptoms data for those individuals in the cohort studies that had COVID-19. The data will be analysed with statistical methods to identify associations between the characteristics of individuals before the pandemic and the severity of the disease. This analysis will be complemented with computer programs developed to predict if the infection of an individual will have serious effects based on his/her characteristics before the pandemic. Machine learning techniques will be used to train computer programs to automatically recognise metabolic features that represent a risk for severe COVID-19.

Impact of research: 
Date proposal received: 
Tuesday, 24 May, 2022
Date proposal approved: 
Monday, 30 May, 2022
Keywords: 
metabolomics, Infection, Computer simulations/modelling/algorithms, Metabolic - metabolism

B4080 - Does LCT predict milk consumption - 30/05/2022

B number: 
B4080
Principal applicant name: 
David A Hughes | University of Bristol MRC-IEU (UK)
Co-applicants: 
Professor Nicholas Timpson
Title of project: 
Does LCT predict milk consumption
Proposal summary: 

A single genetic variant (rs4988235) found in the intron of a the gene MCM6 and located -13,910 base pairs from the gene LCT controls the expression of LCT and the production of lactase, an enzyme required to digest lactose sugar commonly found in fresh milk products. In the ancestral state once infants are weened from breast milk the expression of LCT stops, but in some global human populations, including Europeans, the expression of LCT persists into adulthood and throughout one's life leading to what is commonly referred to as lactase persistence. Here we wish to ask if the genetic variant rs4988235 perviously associated with lactase persistence influences milk consumption in ALSPAC mothers.

Impact of research: 
It will help inform on the direct effect that genotype has on phenotype, a genotype that has been the topic of a great deal of discussion given it is perhaps the best example of local positive selection in humans to date.
Date proposal received: 
Thursday, 26 May, 2022
Date proposal approved: 
Monday, 30 May, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), lactose intolerance, Statistical methods, Genetic epidemiology, Genetics

B4075 - Anxiety and depression in young people who do they affect who seeks treatment and who responds to treatment - 30/05/2022

B number: 
B4075
Principal applicant name: 
Alexandra Pike | University of York (United Kingdom)
Co-applicants: 
Ritwik Niyogi, Toby Wise, Lei Zhang
Title of project: 
Anxiety and depression in young people: who do they affect, who seeks treatment, and who responds to treatment?
Proposal summary: 

Anxiety and depression are common mental health conditions, and represent a major cause of distress and disability in young people. We do not yet understand a) which factors predict vulnerability in young people, b) what predicts who seeks treatment, or c) what characterises young people who respond to treatments compared to those who do not. We need to understand risk factors to allow us to target preventative efforts more effectively. Furthermore, understanding what determines who seeks treatment might allow greater outreach and support to be given to underserved populations, and understanding the factors determining treatment response may allow future research into novel treatments to be targeted, and greater clinical monitoring of those at risk of non-response. Performing this research in young people specifically is important: not only are young people at a critical point in life where they are forming relationships and making decisions about education and careers, but successful treatment access and response might also determine their future mental health. We propose to analyse data from the ALSPAC study, among others, to understand the factors affecting all these parts of young people’s mental health pathways. We also aim to produce an online, interactive, browser-based application that a) researchers, educators, clinicians and policy-makers can use to understand who to target prevention efforts towards, and b) so that young people and their families can have access to the same knowledge as those involved in treating them.

Impact of research: 
We aim to create a digital tool that young people, their families, clinicians, policymakers and researchers can use to understand how to minimise anxiety and depression in young people. We aim to address key unanswered questions that currently limit how effectively we can improve young people’s mental health. In particular, understand the relevant risk factors will allow for greater targeting of preventative efforts, ensuring that we can encourage treatment seeking in underserved populations, and understanding who might need closer clinical monitoring will allow us to use the treatments we already have to better effect, and will hopefully point us in the direction of future treatments.
Date proposal received: 
Thursday, 26 May, 2022
Date proposal approved: 
Monday, 30 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Chronic fatigue, Cognitive impairment, Eating disorders - anorexia, bulimia, Mental health, Computer simulations/modelling/algorithms, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Psychology - personality

B4083 - Social connection as an active ingredient to prevent depression and anxiety in youth - 30/05/2022

B number: 
B4083
Principal applicant name: 
Josefien Breedvelt | National Centre for Social Research
Co-applicants: 
Dr Isabel Taylor
Title of project: 
Social connection as an active ingredient to prevent depression and anxiety in youth
Proposal summary: 

The different types of social connections that young people have when they grow up can affect their mental health. Yet we know very little about how these social factors interact with each other and how they impact the development of depression and anxiety in children and young people. We set out to study how, when and for whom social connections work as an active ingredient for the prevention of common mental health problems (depression and anxiety) in children and young people. We use data collected from ALSPAC to investigate how the development of depression and anxiety was impacted by different types of social connections at different stages of their life. We will use data collected about different types of social relationships experienced by the children and young people at different points in time (such as connections with their family, community, online, teachers and friends) to investigate how these affect development of depression and anxiety over time. We will also analyse data collected from respondents when they were children to see if there is evidence to suggest that social connections in early life affect the development of depression and anxiety at later time points.

Impact of research: 
The impact of this research will be for young people at risk of depression and possibly anxiety, (1) the bivariate estimates can help to identify key social connections to target in the prevention of depression and anxiety, (2) the growth curve analysis can identify which connections matter most at which point they should be addressed (3) interactive visualisation of the non-disclosive results of the modelling can inform researchers, policy makers about the social connections that matter most and further utilise social connections as an active ingredient for preventing depression and anxiety.
Date proposal received: 
Friday, 27 May, 2022
Date proposal approved: 
Monday, 30 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistics, psychology, public mental health

B4082 - Sex stratified acne GWAS meta-analysis - 27/05/2022

B number: 
B4082
Principal applicant name: 
Josine Min | MRC IEU, University of Bristol (United Kingdom)
Co-applicants: 
Dr. Jake Saklatvala, Professor Michael Simpson, Professor Catherine Smith
Title of project: 
Sex stratified acne GWAS meta-analysis
Proposal summary: 

Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Family and twin studies indicate a substantial genetic contribution to acne susceptibility with heritability estimates of 78 and 81%. Genome-wide association studies (GWAS) have made a substantial contribution to the understanding of the genetic basis of several common cutaneous inflammatory disorders. Here we perform a genomewide association analysis, comparing severe cases of acne with controls in females and males separately to identify and replicate genetic determinants.

Impact of research: 
Date proposal received: 
Friday, 27 May, 2022
Date proposal approved: 
Friday, 27 May, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Skin diseases - acne vulgaris, GWAS, Dermatology

B4067 - Adverse Childhood Experiences and the onset of mental health symptom stages - 27/05/2022

B number: 
B4067
Principal applicant name: 
Aswin Ratheesh | Orygen and The University of Melbourne (Australia)
Co-applicants: 
Ms Yufan Chan
Title of project: 
Adverse Childhood Experiences and the onset of mental health symptom stages
Proposal summary: 

Adverse childhood experiences (ACEs), such as abuse, threaten individuals’ life-long
well-being. A growing body of research has supported ACEs’ negative influence on long-term
mental health; however, many existing studies measured ACEs by retrospective self-report, that
is, by adults recalling their childhood experiences. However, there is a need to study
prospectively followed cohorts in order to minimise biases in participant selection and
measurement of ACEs. Examining the impact of ACEs on symptom outcomes conceptualised as
stages could help improve our understanding of the staging model in psychiatry. Therefore, this project proposes to explore the prospective impact of ACEs on the progressive stages of mental disorders in adulthood,

Impact of research: 
This project would provide evidence of ACEs’ prospective impact on adulthood mental health. It would the inform the general public, especially families with children and child protection agencies, of risk and protective factors of the progression of mental disorders. Potential findings would also inform intervention programs; development, protecting children experiencing adverse events from suffering life-long harm.
Date proposal received: 
Wednesday, 25 May, 2022
Date proposal approved: 
Friday, 27 May, 2022
Keywords: 
Epidemiology, Mental health, Statistical methods, Symptoms, stages, onset

B4078 - Genome-wide association study GWAS of lipid traits in adults - 26/05/2022

B number: 
B4078
Principal applicant name: 
Qian Yang | MRC IEU (UK)
Co-applicants: 
Prof Deborah A Lawlor, Prof Nicholas J Timpson
Title of project: 
Genome-wide association study (GWAS) of lipid traits 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 lipid traits (incl. high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides). The main aims of CHARGE’s GWAS are to (1) identify novel loci for lipids trait separately by sex; (2) identify gene-sleep duration interaction effects on lipid traits separately by sex. These analyses will follow the ‘Phase II Analysis Plan for Sleep and Lipids’ version 7.4 provided by CHARGE. Only GWAS summary statistics will be shared with CHARGE. Based on the GWAS results, subsequent analyses (e.g. validation of the gene-by-environment effects using longitudinal data of lipid traits, and Mendelian randomization) would be suggested by CHARGE.

Impact of research: 
This study will help identify novel genetic variants involved in lipid traits and how genetic variants affect these traits taking into account potential interaction with a lifestyle factor, i.e. sleep.
Date proposal received: 
Wednesday, 25 May, 2022
Date proposal approved: 
Thursday, 26 May, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), lipid disorder, GWAS, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4074 - Optimising outcomes in children of depressed parents identification of modifiable promoters of mental health resilience - 26/05/2022

B number: 
B4074
Principal applicant name: 
Stephan Collishaw | Cardiff University (UK)
Co-applicants: 
Ms Egle Padaigaite, Professor Frances Rice, Dr Gemma Hammerton
Title of project: 
Optimising outcomes in children of depressed parents: identification of modifiable promoters of mental health resilience
Proposal summary: 

Parental depression is associated with various mental health conditions and other difficulties in offspring. Nevertheless, some individuals do not develop mental health difficulties or do so only temporarily. It indicates that certain protective factors may buffer risks associated with being raised by a depressed parent. Individual, family, social, and lifestyle protective factors were identified in previous research to be relevant for mental health resilience in adolescence. However, as people mature, different protective factors may be relevant in young adulthood - a peak period for the emergence of mental health problems.

Therefore, this study will aim to understand if various protective factors could explain why some individuals do not develop mental health problems or recover from them despite being at higher risk due to genetic and environmental influences. Furthermore, we will aim to test the causal role of the identified protective factors and potential biological, psychosocial and environmental mechanisms that could explain protective factors’ joint contribution to mental health resilience in children of depressed parents.

We expect to identify modifiable protective factors that could be targeted to develop prevention and intervention strategies that could potentially interrupt the transmission of mental health problems from parents to offspring. In this way, the research could improve the lives of both depressed parents and their offspring.

Impact of research: 
Adolescence and young adulthood is a critical developmental period for developing mental health difficulties that may have long-lasting adverse effects. These difficulties may impact social relationships and education and contribute to poor long-term prognosis. The study will help to better understand mental health resilience and why some individuals do not develop mental health problems or recover from earlier problems despite being at high familial risk. The findings are also expected to identify modifiable targets for evidence-based prevention and intervention strategies, thus improving the lives of both depressed parents and their offspring.
Date proposal received: 
Thursday, 19 May, 2022
Date proposal approved: 
Thursday, 26 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, GWAS, Statistical methods, Development, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B4073 - Mental health trajectories following mental health treatments - 24/05/2022

B number: 
B4073
Principal applicant name: 
Alex Kwong | IEU, PHS
Co-applicants: 
Professor Kate Tilling, Dr Ahmed Elhakeem, Dr Richard Parker
Title of project: 
Mental health trajectories following mental health treatments
Proposal summary: 

Mental health treatments, including antidepressant treatment such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Cognitive Behavioural Therapy (CBT) are effective interventions for depression and anxiety in young people. However, the short and long term effects of one or both of these forms of treatment are unknown in longitudinal population studies. There remains a paucity in how these treatments work, what combination of treatments work, what works best for whom, whether some symptoms are treated better than others and how variable mental health responses are following treatment. We will use data recently collected in ALSPAC on mental health treatments and examine mental health responses to address those research gaps. We will develop a longitudinal research tool which highlights these results which will be made freely available to researchers to apply to other research questions.

Impact of research: 
measuring efficacy of mental health treatment and development of a longitudinal research tool
Date proposal received: 
Wednesday, 18 May, 2022
Date proposal approved: 
Monday, 23 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B4071 - Childhood adversity DNA methylation risk scores and risk for depression across development - 20/05/2022

B number: 
B4071
Principal applicant name: 
Alexandre Lussier | Massachusetts General Hospital (United States)
Co-applicants: 
Dr. Erin C. Dunn
Title of project: 
Childhood adversity, DNA methylation risk scores, and risk for depression across development
Proposal summary: 

Childhood adversity (e.g., abuse or maltreatment, family disruption or dysfunction, poverty, etc.) is one of the most potent life experiences linked to depression, nearly doubling the risk for a first onset. Emerging evidence also suggests that the effects of adversity on depression may vary based on when in the lifespan it occurs. In other words, there may be sensitive periods when the brain is “plastic” and experiences can impart more enduring effects field. However, the biological mechanisms linking childhood adversity to long-term vulnerability for depression remain poorly understood. One possibility is that adversity reprograms the epigenome through DNA methylation (DNAm), epigenetic modifications that do not change the sequence of the genome, but can alter gene expression. Recent evidence also suggests that DNAm risk scores (MRS) generated from large-scale studies of early-life exposures and/or mental outcomes may help predict and interpret risk for depression and other mental disorders.

To this end, we recently completed the largest analysis of time-varying childhood adversity and genome-wide DNAm in childhood, analyzing the impact of five types of adversity across seven longitudinal birth cohorts (N=2,347-3,279). Through these analyses, we identified distinct epigenetic signatures for five types of childhood adversity, as well as further evidence of sensitive periods for the effects of adversity on DNAm. However, it remains unknown whether DNAm risk scores generated from these data can accurately explain and predict depression risk across development.

As such, we seek to extend this research, which included data from the ALSPAC cohort, to further investigate the relationship between childhood adversity, DNAm, and depressive symptom trajectories across development. The central hypothesis we will test is that DNA methylation patterns linked to childhood adversity can be used as predictors of both prior exposures to adversity and future depressive outcomes, with measurable effects on depressive symptom trajectories.

Impact of research: 
By testing our central hypothesis, we will determine whether composite measures of childhood adversity can be identified through epigenetic alterations and whether these biological measures can predict the onset and severity of psychopathology. As the first longitudinal investigation of DNA methylation risk scores for childhood adversity and depression, this research the stage for a broader research program aimed at determining how epigenetic mechanisms can be used to predict and interpret risk for mental illness across the life course. Importantly, this work will help identify the molecular mechanisms that drive risk for depression across development, as well as delineate the periods when childhood adversity and DNA methylation have greater effects on depression risk, which will help guide optimally-timed interventions to reduce the burden of depression. Such efforts will help target prevention and treatment efforts to people who are at higher risk for mental illness and ultimately, will help improve the overall well-being of youth and adults affected by depression.
Date proposal received: 
Friday, 13 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Computer simulations/modelling/algorithms, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Epigenetics, Genetics

B4069 - Autistic traits anxiety and eating behaviours Longitudinal trajectories across child development - 20/05/2022

B number: 
B4069
Principal applicant name: 
Moritz Herle | Kings College London (United Kingdom)
Co-applicants: 
Dr Helena Zavos , Dr Virginia Carter Leno
Title of project: 
Autistic traits, anxiety, and eating behaviours: Longitudinal trajectories across child development
Proposal summary: 

Recent empirical work suggests the prevalence of eating disorders may be raised in autistic individuals, however, questions remain as to whether the co-occurrence of autism and eating disorders could be due to selective samples and/or difficulties disentangling symptoms of autism as compared to symptoms of eating disorders. An alternative explanation is that autism, or high levels of autistic traits, in childhood, may causally increases risk for eating disorders later in development. In addition, autistic children often experience high level of anxiety, and might use overeating or binge eaitng as a coping strategy to sooth and calm themselves down, which might put them on increased risk for later eating disorders. Further research into the pathways and potential mediators of the link between autism, anxiety,and eating disorders is needed to illuminate underpinning mechanisms, which in turn will highlight targets for prevention/intervention.

Impact of research: 
Date proposal received: 
Friday, 20 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Eating disorders - anorexia, bulimia, Mental health, Statistical methods, Statistical methods

B4072 - Subtypes of persistent developmental stammering - 20/05/2022

B number: 
B4072
Principal applicant name: 
Michel Belyk | Edge Hill University (United Kingdom)
Co-applicants: 
Title of project: 
Subtypes of persistent developmental stammering
Proposal summary: 

There are speech therapies that can help them to cope, but most children will recover on their own. However, about one person in every hundred keeps stammering into adulthood. Stammering is tends to run in families, which means that it is genetic. There are also markers in the brain that help us to understand how stammering happens. However, they don’t seem to be very consistent across people. This project proposes to use a big data base of Magnetic Resonance Imaging (MRI) and genetics data covering thousands of parents and children, many of whom will have stammered. These data will be used to understand both how the brains of people who stammer are different from fluent speakers, and how they are different from each other. With a greater understanding of what makes some brains stammer, it is hoped that we can inform the development of better speech therapies. People who stammer also have a strong interest in understanding why they are the way they are and are growing community advocacy movements around the idea of neurodiversity. These advocacy groups will benefit as we learn just how diverse their brain can be.

Impact of research: 
Stammering may be amenable to a personalised medicine approach to speech-therapy. Speech and language therapists train people who stammer to use techniques that either enhance fluency or enable stammering in a more controlled manner, usually by changing some aspect of the way that they speak. This may include interventions related to muscle tension, speech timing, auditory feedback, as well dealing with anxiety about the prospect of stammering. These therapies have good efficacy when measured at the clinic, but high rates of relapse (~70%) as patients frequently discontinue the techniques learned in therapy when faced with real-world communication. Understanding variability in the underlying causes of stammering is an initial step towards a personalised medicine approach to speech therapy. Understanding individual differences in the underlying neurobiology of stammering may be used to generate testable predictions about which treatments connect with the mechanisms underlying an individual patient’s condition – matching patients with the treatments that most closely address underlying causes of their stammer. The stammering community are beginning to understand and reference their condition as a form of neurodiversity, in line with contemporary trends that have improved quality of life for people on the Autism Spectrum. In addition to the implications of the proposed research for understanding aetiology and improving treatment, the proposed research aligns directly with the broader advocacy interests of people who stammer.
Date proposal received: 
Tuesday, 17 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Speech/language problem, Medical imaging, Speech and language

B4068 - Understanding the mechanisms linking the urban environment to mental health in childhood adolescence and early adulthood - 25/05/2022

B number: 
B4068
Principal applicant name: 
Joanne Newbury | University of Bristol
Co-applicants: 
Prof Stan Zammit
Title of project: 
Understanding the mechanisms linking the urban environment to mental health in childhood, adolescence, and early adulthood
Proposal summary: 

Individuals who are raised in urban (versus rural) settings are around twice as likely to develop a psychotic disorder such as schizophrenia. Research also suggests that risk for other mental health problems, in particular depression, anxiety and conduct problems, is elevated in urban settings. Given that 70% of the world’s population will live in urban areas by 2050, it is essential that we uncover the pathways linking cities and psychosis so that we can inform intervention efforts.
Air and noise pollution are among the biggest environmental health risks that the world faces, and are particularly problematic in cities. Growing evidence also suggests that air pollution may contribute to the development of mental health problems. However, it is currently unknown whether air and noise pollution might partly explain the elevated risk for mental health problems found in cities. In addition, there has been a lack of longitudinal research, including that using pollution spanning the early years of development. Studies have also often been inadequately controlled for potential confounders.
This project will examine 1) the longitudinal associations of air pollution exposure from pregnancy to age 15 with psychotic experiences at age 12, 18, and 24; and examine specificity by repeating analyses with anxiety, depression, and conduct problems as outcomes; 2) explore the interplay between neighbourhood social characteristics (crime and social fragmentation) and air pollution in the emergence of psychotic experiences, and 3) examine two potential biopsychological mechanisms linking urban neighbourhood exposures with mental health, namely inflammation and cognition.

Impact of research: 
This research will serve a range of stakeholders, including researchers, industry, policymakers, and the general public. Air pollution is a known cause of physical disease, but very little is known about the impact of air pollution on mental health problems. My research will contribute to the evidence base on air pollution and mental health, which is essential for policymakers to make the economic case for tightening air pollution restrictions. Though a major global challenge, urban expansion nevertheless provides a unique opportunity for promoting healthy urban design. My research will also be useful to industry and policymakers to provide evidence for targets in the urban environment that could be modified to improve mental health. By identifying modifiable targets in the urban environment, this research has the strong potential to improve the mental health of urban residents now and for years to come. My plan for maximising impact of the findings is as follows: 1) I expect that the research proposed will lead directly to at least four publications in highly regarded journals with a broad readership. 2) I will disseminate findings via oral presentations at six international psychiatry/epidemiology conferences that attract a wide audience such as MQ Mental Health Science Meeting. 3) I will liaise with press teams such as the Science Media Centre to maximise the impact of the findings through press releases and press briefings. 4) I will ensure that findings are clearly presented to the public by preparing blogs and podcasts, and by participating in interactive open workshops and talks. 5) I will share my findings with policymakers by holding a policy lab with support from Policy Bristol.
Date proposal received: 
Wednesday, 11 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Cognitive impairment, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4040 - CADSET proposal Obstructive lung function phenotypes and early life - 20/05/2022

B number: 
B4040
Principal applicant name: 
Raquel Granell | MRC Integrative Epidemiology Unit (MRC-IEU) (United Kingdom)
Co-applicants: 
Prof Anna Hansell, Miss Katie Eminson, Professor John Gulliver, Miss Yoni van Dijk
Title of project: 
CADSET proposal: Obstructive lung function phenotypes and early life
Proposal summary: 

It is crucial to understand which early-life factors influence lung function development, since impaired lung function has been associated with respiratory, cardiovascular and metabolic anomalies, and even all-cause mortality. This project will focus on further understanding how lung function develops and what early life factors are key at imparing its development.

Impact of research: 
It is intended to publish results in high impact journals at the end of the project, which might contribute to policy decision-making and/or future follow-up studies.
Date proposal received: 
Thursday, 5 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B4062 - C-section Delivery and blood DNA Methylation at Birth and in Childhood - 20/05/2022

B number: 
B4062
Principal applicant name: 
Giulia Mancano | University of Bristol (United Kingdom)
Co-applicants: 
Ms Fernanda Morales Berstein, Dr Hannah Elliott, Dr Gemma Sharp, Dr Rebecca Richmond, Dr Marie-France Hivert , Joanne Sordillo
Title of project: 
C-section Delivery and blood DNA Methylation at Birth and in Childhood
Proposal summary: 

Emerging evidence suggests that babies born by C-section (Cesarean section) have different hormonal, physical, bacterial, and medical exposures, and that these exposures can subtly alter neonatal physiology. (Sandall et la, 2018) C-section delivery has been associated with a number of chronic disease outcomes in children, including metabolic risk phenotypes and asthma. One of the potential mechanisms through which C-section delivery may increase risk of adverse health outcomes is via epigenetic alterations. (Dahlen et al, 2013)

Dahlen, HG et al. “The EPIIC hypothesis: intrapartum effects on the neonatal epigenome and consequent health outcomes.” Med Hypotheses. 2013. May; 80(5):656-62.

Sandall, J et al. “Short-term and long-term effects of caesarean section on the health of women and children.” Lancet. 2018. Oct 13; 392(10155):1349-1357.

Impact of research: 
This research will contribute to the identification of novel differentially methylated CpG sites in the offspring, and therefore, to our understanding of epigenetic mechanisms underlying observed associations between mode of delivery and adverse offspring health outcomes.
Date proposal received: 
Friday, 20 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., DNA methylation, Birth outcomes, Epigenetics, Microbiome, Offspring

B4064 - Associations of diabetic traits blood pressure general and central adiposity with COVID-19 and long COVID a prospective study - 20/05/2022

B number: 
B4064
Principal applicant name: 
Nic Timpson | MRC-IEU
Co-applicants: 
Fergus Hamilton
Title of project: 
Associations of diabetic traits, blood pressure, general and central adiposity with COVID-19 and long COVID: a prospective study
Proposal summary: 

COVID-19 patients with high BMI and waist to hip ratio (WHR), diabetes and hypertension showed a higher risk of dying and severe disease in the early pandemic (1-3), but the role in susceptibility for COVID-19 and long COVID and the extent to which associations are due to confounding is still mostly unclear (4-7). Previous analysis on infection and long Covid risk mainly used binary measures of obesity or overweight, known diabetes status and hypertension, which could introduce measurement error, reduce statistical power, and does not allow to disentangle whether an association is related to treatment or due to the disease itself. Using pre-pandemic diabetes, measured blood glucose and HbA1c, BMI, WHR, body fat and blood pressure could improve measurement quality by identifying disease control, severity, and those with prediabetes.

Impact of research: 
Help understand impact of BMI, weight, height, and other linked variables on long covid.
Date proposal received: 
Tuesday, 17 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Immunology, Infection, GWAS, Biological samples -e.g. blood, cell lines, saliva, etc.

B4066 - Exploring the pathways between mental health symptom stages from early adolescence to young adulthood - 20/05/2022

B number: 
B4066
Principal applicant name: 
Aswin Ratheesh | Orygen and The University of Melbourne (Australia)
Co-applicants: 
Ms Sarah Walmsley
Title of project: 
Exploring the pathways between mental health symptom stages from early adolescence to young adulthood
Proposal summary: 

Early adolescence is a sensitive period of significant social and physiological growth, and represents the time when symptoms of mental disorders commonly emerge. Clinical staging models have been proposed to provide framework for identifying early risk factors and symptoms in adolescence and young adulthood, that may predict future progression to mood disorders and psychosis. It has been suggested that sub-threshold symptoms may be predictive of later stages of more serious mental disorders. We propose to examine the associations between parent rated sub-threshold mental health symptoms in early adolescence and mental health symptom stages in young adulthood. This will help determine which of these symptoms could represent risk of progression to stages associated with need for care. Parents offer unique insight into early mental health symptoms, observing their children in a home environment. It is important to understand the trajectories associated with parental accounts. If specific parent rated sub-threshold symptoms in early adolescence can be identified, that are predictive of progression to later stages of mood, anxiety and psychotic symptom stages in young adulthood, this could provide understanding of prognosis and intervention needs to adolescents and their families. Cannabis use, alcohol use and negative life events may mediate the relationship between parent rated symptoms in early adolescence and mental health difficulties in young adulthood. We propose to analyse these pathways in order to understand whether these factors are associated with increased risk of progression to later clinical stages. This project will contribute to understanding the validity of clinical staging models for psychotic and mood disorders in youth mental health, in particular contributing to understanding of early risk factors in these models, and could provide opportunities for targeted intervention and prevention.

Impact of research: 
If parent rated sub-threshold symptoms in early adolescence can be identified that are predictive of progression to later clinical stages in young adulthood, this could assist in the understanding of prognosis and early intervention needs for adolescents and their parents and treating teams. Additionally, if risk factors can be identified that are associated with worse outcomes, including cannabis use, alcohol use and negative life events, this could provide opportunity for targeted intervention to reduce or prevent progression from early sub-threshold stages to later clinical stages and increased need for care.
Date proposal received: 
Wednesday, 11 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Epidemiology, Mental health, Statistical methods, Staging, symptoms, onset

B4070 - Rapid evaluation of interventions for close contact infectious diseases - 31/05/2022

B number: 
B4070
Principal applicant name: 
Ellen Brooks Pollock | University of Bristol (United Kingdom)
Co-applicants: 
Dr Leon Danon, Dr Amy Thomas, Dr Emily Nixon, Prof Nicholas Timpson, Dr Kate Northstone
Title of project: 
Rapid evaluation of interventions for close contact infectious diseases
Proposal summary: 

During the COVID-19 pandemic, ALSPAC ran a rapid survey of risk mitigation behaviours. We used the data to inform a transmission model of the SARS-CoV-2 Omicron-variant wave. We would like to develop the methods we started during the COVID-19 pandemic to create a public health decision-making tool. We propose to work with the ALSPAC cohort to characterise infection prevention practices and to understand the trade-offs between measures.

Impact of research: 
We are developing a tool for public health decision makers to use. The impact will be an increased evidence-base for public health decisions.
Date proposal received: 
Tuesday, 17 May, 2022
Date proposal approved: 
Friday, 20 May, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Infection, Mathematical/infectious disease modelling, Infectious diseases

B4065 - The Impact of Early Child Development on Social Mobility in the UK - 13/06/2022

B number: 
B4065
Principal applicant name: 
Matt Dickson | University of Bath (United Kingdom)
Co-applicants: 
Mrs Rachel Ambler
Title of project: 
The Impact of Early Child Development on Social Mobility in the UK
Proposal summary: 

The main research question that this project will address is: how do parental investments and parenting practices in the pre-school years influence the formation of human capital in children and contribute to the transmission of socio-economic status between generations.

During the pre-school years, though there are many outside influences on children, it is parents that have the greatest impact on their offspring. Parental investments before the age of three are likely to be as important, if not more, than what happens from age three onwards, given the dynamic complementarity between early and later skill development.

The project aims to extend our understanding of how (and when) gaps in attainment across socio-economic status emerge. We will map the relationships between measures of parental investment in the early years and long-term socio-economic outcomes and investigate the extent to which these are mediated through educational attainment. The empirical analysis will use data from the Avon Longitudinal Study of Parents and Children (ALSPAC) with linkage to the National Pupil Database. The data will be used to empirically investigate the extent of differences in early child investments and parenting practices between children/parents and how any differences relate to the later life outcomes of the children.

Impact of research: 
This project will identify the key parental investments in the very earliest years of life which lead to long-term economic success. The over-arching aim is to increase social mobility. To date, research in this domain has focused on experience from pre-school (age 3) onwards, neglecting the role of the very earliest years for human capital formation. We will add to the literature and policy understanding by more precisely quantifying how early-life investments and experiences help, or hinder, social mobility. We will quantify the relative size of the well-documented achievement gaps at school entry between advantaged and disadvantaged children, identifying when and, importantly, why they start to increase. The research will help to inform policy by uncovering which everyday parenting practices during infancy enhance outcomes later in life so we can make robust policy recommendations regarding the timing of targeted interventions in the earliest years of life, and even pre-birth. We will argue that early childhood should be an integral part of policy decisions; using this analysis to show that the role of the earliest phase of life for human capital formation is pivotal in understanding, and overcoming, the inequality and disadvantage that persist for many families. The force of this argument will be underpinned by data from four generations, uniquely available in the ALSPAC, which presents an exciting opportunity to expand our understanding of intergenerational mobility. Our findings will be of interest to policymakers in the Dept. for Education, the Dept. for Health and Social Care, and the Office of the Children’s Commissioner, as well as the Social Mobility Commission and we will actively engage with them. Understanding the role of the earliest interactions between parents and their children in the transmission of socio-economic status from one generation to the next will help in the design of policies aimed at increasing social mobility and widening opportunity, with the potential for significant long-term impact.
Date proposal received: 
Monday, 9 May, 2022
Date proposal approved: 
Monday, 16 May, 2022
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Intelligence - memory, Linkage, Parenting, Social science, Statistical methods

B4063 - Determinants of breastfeeding success and health inequalities - 10/05/2022

B number: 
B4063
Principal applicant name: 
Nancy McBride | MRC IEU (United Kingdom)
Co-applicants: 
Dr Luisa Zuccolo, Dr Carolina Borges, Emma Benham
Title of project: 
Determinants of breastfeeding success and health inequalities
Proposal summary: 

Breastfeeding is sustainable, the biological norm, and potentially life-saving, particularly for premature babies. Evidence-based strategies to support breastfeeding have been successful, but inequalities in breastfeeding rates are proving difficult to reduce, affecting the most vulnerable of mothers and babies. Successfully establishing and sustaining breastfeeding can be facilitated by both removing structural and cultural barriers, and overcoming individual challenges. Common factors such as obesity and depression/anxiety could play an important part in explaining some of the variability (and inequality) in breastfeeding duration. Conversely, maternal factors reflecting good mental and physical health could increase resilience to contexts with low systemic and cultural support for breastfeeding, such as the UK. However, the evidence on the individual determinants causally influencing successful and sustained breastfeeding is of poor quality. The identification of causal determinants of early cessation will improve breastfeeding support activities.

Impact of research: 
We hope to identify causal determinants of early cessation - this can then be used to improve breastfeeding support activities.
Date proposal received: 
Wednesday, 4 May, 2022
Date proposal approved: 
Tuesday, 10 May, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Birth outcomes

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