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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B3703 - Development of mental illness and cardiometabolic comorbidities - 25/01/2021

B number: 
B3703
Principal applicant name: 
Rona J Strawbridge | University of Glasgow (Scotland)
Co-applicants: 
Professor Daniel J Smith, Dr Breda Cullen, Dr Donald Lyall, Dr Joey Ward
Title of project: 
Development of mental illness and cardiometabolic comorbidities
Proposal summary: 

It is well known that severe mental illness (such as schizophrenia, bipolar disorder and major depressive disorder) gives an increased risk for cardiometabolic diseases (including obesity, type 2 diabetes and heart disease). Recent evidence suggests that there are biological mechanisms that are shared by mental illness and cardiometabolic disease. This project will explore whether the associations between genetics, mental illness and cardiometabolic disease that we have reported in adults are already apparent in adolescents. Mental illness frequently presents during adolescence, with cardiometabolic diseases typically being diagnosed decades later. If the associations between genetics, mental illness and cardiometabolic diseases that we have observed in adults are detectable in adolescents, this research could pave the way for improved treatment of mental illness as well earlier prevention of cardiometabolic disease. Improving symptoms and slowing down progression to long term complications of mental illness has the potential to greatly enhance quality of life as well as reducing health inequalities and the healthcare costs associated with severe mental illness.

Impact of research: 
If the associations between genetics, mental illness and cardiometabolic diseases that we have observed in adults are detectable in adolescents, this research could pave the way for improved treatment of mental illness as well earlier prevention of cardiometabolic disease. Improving symptoms and slowing down progression to long term complications of mental illness has the potential to greatly enhance quality of life as well as reducing health inequalities and the healthcare costs associated with severe mental illness.
Date proposal received: 
Tuesday, 19 January, 2021
Date proposal approved: 
Monday, 25 January, 2021
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Diabetes, Hypertension, Mental health, Obesity, Pain, cardiovascular disease psychiatric illness, Computer simulations/modelling/algorithms, GWAS, Statistical methods, polygenic risk scores Mendelian randomisation Linkage disequilibrium score regression, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Blood pressure, Genome wide association study, Intelligence - memory, Mendelian randomisation, Metabolic - metabolism, Psychology - personality, Physical - activity, fitness, function, Sex differences, Sleep, Statistical methods, BMI, Cardiovascular, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Genetic epidemiology, Genetics, Genomics

B3705 - Predictors for biological age and age-associated diseases - 25/01/2021

B number: 
B3705
Principal applicant name: 
Jennifer Harris | Norwegian Institute of public health (Norge)
Co-applicants: 
Øyvind Helgeland, PhD, Håkon Bøås, Astanand Jugessur, Arne Vasli Lund Søraas, MD, PhD, Espen Riskedal, MSc, Karl Trygve Kalleberg, MD, PhD, Cathrine Lund Hadley, MD, PhD
Title of project: 
Predictors for biological age and age-associated diseases
Proposal summary: 

We want to better understand why some people develop certain disease as they age, while others don’t. We think that by looking at how our genes change their behavior as the body grows older, we can gain new insights into how the aging process leads to disease, and into the aging process itself. This is not only relevant to the typical diseases of the elderly (e.g. rheumatoid arthritis, heart disease, diabetes, dementia and cancer), but also to younger people who develop diseases that are occur at specific age intervals (e.g. MS, infertility, certain cancers).
The project will perform advanced mathematical analyses of the regulation of genes, to develop new computer methods that can predict and explain the development of disease. Our goal is to eventually make new diagnostics, such as blood tests, that can be used to catch age-related diseases earlier and more accurately, so that patients will receive earlier and better treatment.

Impact of research: 
Better and earlier diagnosis of rheumatoid arthritis
Date proposal received: 
Sunday, 24 January, 2021
Date proposal approved: 
Monday, 25 January, 2021
Keywords: 
Epigenomics, Bone disorders - arthritis, osteoporosis, Cancer, Cognitive impairment, Fertility/infertility, Hypertension, Infection, Computer simulations/modelling/algorithms, DNA sequencing, Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Bones (and joints), Epigenetics

B3698 - Longitudinal associations between physical activity and sleep in early adolescence - 20/01/2021

B number: 
B3698
Principal applicant name: 
Dr. Russell Pate | University of South Carolina (United States of America)
Co-applicants: 
Agnes Bucko, MS
Title of project: 
Longitudinal associations between physical activity and sleep in early adolescence
Proposal summary: 

Meeting physical activity, sleep and sedentary behavior guidelines is associated with better cardiometabolic health and adiposity outcomes among children and youth. Unfortunately, recent estimates suggest that only 25.4% of adolescents in the US meet sleep guidelines, 26.1% meet physical activity guidelines, and only 5% meet guidelines for sleep, physical activity and sedentary behavior. Although some evidence indicates that there is a positive association between physical activity levels and sleep duration, findings among children and adolescents are not consistent and are limited by a predominantly cross-sectional study design. Although low income and minority youth are at a higher risk of not meeting both sleep and physical activity recommendations, it is unclear whether the sleep and physical activity relationship varies by racial, ethnic or socioeconomic group. Furthermore, exercise intensity appears to have a strong, positive relationship with sleep, although more research is needed to determine whether exercise at a light or moderate intensities can lead to improvements in sleep outcomes. This study aims to examine the association between physical activity and sedentary behavior, measured objectively at 11, 13 and 15 years of age, with subjectively-measured sleep at age 15. Furthermore, this study aims to understand whether the sleep and physical activity relationship varies by demographic characteristics and measures of adiposity.

Impact of research: 
This project is significant because it will utilize a longitudinal study design to assess the relationship between sleep and physical activity, which will aid in understanding whether physical activity interventions can be utilized to improve sleep outcomes in adolescents. Furthermore, this study will expand our knowledge on the association between sleep and sedentary behavior. Although some research supports an inverse association between sleep and sedentary behavior, the lack of longitudinal studies on this association makes it difficult to discern whether sedentary behavior has a negative effect on sleep outcomes, or if children who are poorer sleepers are less active as a result of increased tiredness during the day. This study will go beyond current research addressing the sleep and physical activity/sedentary behavior relationship by assessing sleep quality, and not just sleep duration, and will consider whether these associations vary by different demographic characteristics.
Date proposal received: 
Tuesday, 12 January, 2021
Date proposal approved: 
Wednesday, 20 January, 2021
Keywords: 
Exercise Science , Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Physical - activity, fitness, function

B3682 - NCS Cohort Project ARQ2 COVID-19 and long COVID - 20/01/2021

B number: 
B3682
Principal applicant name: 
Ruth Mitchell | University of Bristol (United Kingdom)
Co-applicants: 
Dr Kate Northstone, Dr Jazz Croft, Dr Alex Kwong, Dr Gareth Griffith, Professor Nic Timpson
Title of project: 
NCS Cohort Project, ARQ2, COVID-19 and long COVID
Proposal summary: 

For some people, coronavirus (COVID-19) can cause symptoms that last weeks or months after the infection has gone. This has been called post-COVID-19 syndrome or "long COVID". Common symptoms include fatigue, shortness of breath, chest pain or tightness, difficulty sleeping, joint pain, problems with memory and concentration ('brain fog'). Little is known about what causes long COVID and very little about how to treat long COVID. This project aims, in a first instance, to investigate risks and determinants that make an individual more likely to have long COVID, and then to understand the health consequences of long COVID. This is of critical public health importance in helping to treat, prevent and mitigate consequences of long COVID.

Impact of research: 
Findings will contribute to the evidence base of risk factors for long COVID. It will help target prevention measures at the vulnerable groups.
Date proposal received: 
Thursday, 14 January, 2021
Date proposal approved: 
Wednesday, 20 January, 2021
Keywords: 
Epidemiology, COVID-19, Statistical methods, COVID-19

B3700 - Maternal Lifestyle Score during Pregnancy and Child Internalizing and Externalizing Problems - 20/01/2021

B number: 
B3700
Principal applicant name: 
Jordi Julvez | ISGLOBAL (Spain)
Co-applicants: 
MSc Raquel Garcia Esteban
Title of project: 
Maternal Lifestyle Score during Pregnancy and Child Internalizing and Externalizing Problems
Proposal summary: 

Maternal life style factors during pregnancy has been related to child neurodevelopment and behavioral problems. However, there is a need to further study them in combination as a general score and perform the analyses in a consortium of several European cohorts. The harmonization of mental health problems in several population-based birth cohorts will allow us to perform trajectory analyses with specific mental health domains. In this study, we will study the association of a maternal lifestyle score during pregnancy and the trajectories of internalizing and externalizing problems. These are the main domains in child neurobehavioral development. The creation of the lifestyle score will be based on different lifestyle variables reported during pregnancy: Smoking, Alcohol consumption, DASH diet, folic acid supplement, pre-pregnancy weight/height, sleep duration, physical activity and tv watching. We will create a maternal healthy lifestyle score (CHLS) using the dichotomous variables. The final summation of these variables will be used as the main exposure variable.

Impact of research: 
The impact of this study will be important because there is not much scientific literature assessing lifestyle score factors during pregnancy and joining different European cohorts together.
Date proposal received: 
Friday, 15 January, 2021
Date proposal approved: 
Wednesday, 20 January, 2021
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development

B3702 - Understanding pathways from social transitions in emerging adulthood to later health outcomes - 25/01/2021

B number: 
B3702
Principal applicant name: 
Annie Herbert | University of Bristol (United Kingdom)
Co-applicants: 
Prof. Laura Howe, Dr. Jon Heron
Title of project: 
Understanding pathways from social transitions in emerging adulthood to later health outcomes
Proposal summary: 

There are key transitions that often occur when adolescents become adults, such as leaving full-time education, starting a full-time job, living with a partner, or becoming a parent. In previous generations, when these transitions happen early or happen close together, they have been shown to be related to poorer health and related behaviours, for example, weight gain or increased smoking. However, there is little evidence available on what typical transition patterns look like for today’s young people, which patterns are the most harmful to health, or the reasons that these patterns cause poorer health (for example, is weight gain in those who have made lots of these transitions early in life explained more by the extra stress or by lack of time to eat healthily or exercise). Using data from two recent UK birth cohorts, and sophisticated methods of analysis, we will try to answer these questions. Where possible, we will see if findings differ for sex, ethnic minority, and LGBTQ+ groups. This information can help us understand the best way to support young people moving from adolescence to young adulthood, to help optimise their health later in life.

Impact of research: 
The findings will better inform policymakers and the transitions research community as to whether AST patterns have changed in recent generations, given changing cultures in educational policy and other initiatives and trends over time e.g. preventing teenage pregnancy, closing the gender gap in employment, cohabitation over marriage. We aim to identify high-risk groups for sub-optimal AST patterns in terms of health, and modifiable risk factors, particular pathways, and critical time-points, where intervention to prevent secondary poor health outcomes may be particularly effective.
Date proposal received: 
Monday, 18 January, 2021
Date proposal approved: 
Wednesday, 20 January, 2021
Keywords: 
Epidemiology, Diabetes, Mental health, Obesity, Respiratory - asthma, GWAS, Statistical methods, Genome wide association study, Injury (including accidents), Linkage, Mendelian randomisation, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Sex differences, Social science

B3253 - Inclusion of ALSPAC samples in Psychiatric Genomics Consortium PGC for ED - 14/01/2021

B number: 
B3253
Principal applicant name: 
nadia Micali | University of geneva, Switzerland; UCL, UK
Co-applicants: 
Cynthia Bulik, Gerome breen, Mohamed Abdulkadir, Jonathan Coleman, Melissa Anne Munn-Chernoff, Jet Termorshuizen, Sang Hyuck Lee
Title of project: 
Inclusion of ALSPAC samples in Psychiatric Genomics Consortium (PGC) for ED
Proposal summary: 

Eating disorders (ED) such as anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) are common psychiatric disorders with life-long health impacts. Additionally, current treatment options have limited effectiveness, highlighted by the observation that only 30% of adult patients with AN fully recover. The development of EDs is highly complex and driven by environmental and genetic factors. Previous research has suggested that EDs run in families, but the specific genetic variants associated with risk for EDs are not well understood. Twin studies have shown that the heritability for EDs ranges from 40%-70%. Similarly, to other psychiatric disorders, such as depression or schizophrenia, many genetic variants with relatively small effect underlie the overall genetic risk for EDs. Due to the nature of these effects, extremely large sample sizes are necessary which can only be amassed by international efforts. For AN previous large scale genetic studies, comparing patients with healthy controls, have been successful in pinpointing genetic variants associated with the illness (Duncan et al., 2017). However, no such attempts have been made regarding BN or BED and the field of EDs is lacking behind the genomic discovery of other psychiatric disorders. The success of these studies, which search across the entire genome to find associated genetic markers, is highly dependent on the number of patients and controls included in the research because the sample sizes defines the statistical power to detect significant associations. Thus, worldwide joint forces are necessary to combine datasets to boost sample sizes. Therefore, we propose to include ALSPAC participants in the international approach: Using the rich database of ALSPAC to identify patients diagnosed with AN, BN or BED and add them to international cohorts examining the genetic architecture of EDs. The findings may provide a better understanding of the development of EDs and may help to identify or new treatment strategies including potential targets for pharmaceutical treatment.

Impact of research: 
The identification of genomic variants associated with EDs may enable researcher to understand the underlying biology and may ultimately inform the development of new treatments. Only one FDA-approved medication targets the core symptoms of an eating disorder (in this case binge eating) and mortality is high. An international collaboration lead by the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) with the Anorexia Nervosa Genetics Initiative (ANGI) and iPsych (Denmark) has found eight loci for anorexia nervosa with promising single gene loci being potential druggable targets. We also see that anorexia has strong psychiatric and metabolic genetics, suggesting a reconceptualization of the illness is needed. We seek to perform a meta-analysis of our GWAS results with ALSPAC to extend genomic discovery in all eating disorders. We aim to improve detection, prevention, and ultimately to develop cures to reduce and ultimately eliminate mortality from eating disorders.
Date proposal received: 
Monday, 21 December, 2020
Date proposal approved: 
Thursday, 14 January, 2021
Keywords: 
Genetics, Eating disorders - anorexia, bulimia

B3684 - NCS Cohort Project ARQ5 COVID-19 and historical health - 20/01/2021

B number: 
B3684
Principal applicant name: 
Ruth Mitchell | University of Bristol (United Kingdom)
Co-applicants: 
Dr Kate Northstone, Dr Jazz Croft, Dr Alex Kwong, Dr Gareth Griffith, Professor Nic Timpson, Dr Dylan Williams
Title of project: 
NCS Cohort Project, ARQ5, COVID-19 and historical health
Proposal summary: 
Impact of research: 
Findings will contribute to the evidence base of risk factors for COVID prognosis. It will help target prevention measures at the vulnerable groups.
Date proposal received: 
Tuesday, 12 January, 2021
Date proposal approved: 
Thursday, 14 January, 2021
Keywords: 
Epidemiology, COVID-19, Statistical methods, Immunity

B3699 - The use of nurseries in the age of COVID - 15/01/2021

B number: 
B3699
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Professor Nic Timpson, Dr Ellen Brooks Pollock, Dr Amy Thomas
Title of project: 
The use of nurseries in the age of COVID
Proposal summary: 

There is mounting pressure on the government to close nurseries in the current COVID lockdown. There is little data available to assist policy makers in making this decision. ALSPAC is a unique position with our second generation of children, many of whom will be of pre-school age. In the first instance this project will determine whether COVID cases are more or less likely in the parents of children of nursery age. Depending on the results we may approach parents to complete a brief questionnaire on whether their children are currently attending nursery and what the consequences might be if their current provieer were to close.

Impact of research: 
provide evidence for policy makers to assist with the decision whether or not to close nurseries during the current lockdown
Date proposal received: 
Tuesday, 12 January, 2021
Date proposal approved: 
Wednesday, 13 January, 2021
Keywords: 
Epidemiology, COVID

B3696 - Impact of immune sex differences in the first 1000 days of life - 12/01/2021

B number: 
B3696
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Co-applicants: 
Philip Goulder, Professor
Title of project: 
Impact of immune sex differences in the first 1000 days of life
Proposal summary: 

Substantial differences exist between the immune reponses made by males and females that critically impact health and survival. Typically, females make stronger immune responses to vaccines and infections and achieve superior outcomes throughout life. For example, females achieve the same levels of neutralizing antibodies from half the dose of influenza vaccine as males from the full dose. However, this more exuberant immune response leads to greater susceptibility to immunopathology and autoimmune diseases and more adverse events from immunizations. To complicate matters, there are exceptions; as fetuses, females have a 2-fold greater susceptibility to mother-to-child transmission of both HIV and HCV infection, and to IFN-I-resistant viruses. To better understand the mechanisms responsible for these complex observations, we propose to compare the epigenetic and hormonal responses in males and females to immunization and vaccination in early life. We hypothesize that life-long immune sex differences are established early through the interplay of host genetics, sex-specific steroid biosynthesis, epigenetics and the environment, and that early-life epigenetic changes in response to sex-specific steroid modulation and infection and immunization play a dominant role in this process.

Impact of research: 
In the short-term, we hope to better understand the mechanism responsible for sex-specific immune responses. In the long-term, improved understanding of these mechanisms should provide the rationale to tailor vaccines and treatments and improve patient outcomes.
Date proposal received: 
Thursday, 7 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Immunology, Infection, Microarrays, Proteomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Environment - enviromental exposure, pollution, Epigenetics, Immunity, Sex differences

B3688 - Mapping Neurodevelopmental Trajectories for Adult Psychiatric Disorder A focus on Autism and Psychosis - 20/01/2021

B number: 
B3688
Principal applicant name: 
Anthony David | UCL
Co-applicants: 
Miss Sarah Ashley
Title of project: 
Mapping Neurodevelopmental Trajectories for Adult Psychiatric Disorder: A focus on Autism and Psychosis
Proposal summary: 

This project will investigate neurodevelopmental trajectories for psychiatric disorders, in particular autism and subclinical autistic traits and their overlap with psychosis and psychotic experiences, using longitudinally acquired MRI data from the ALSPAC-MRI-I + II datasets. Analyses will explore the influence of environmental (perinatal and postnatal) and genetic exposures on behaviour. Multi-modal brain imaging scans will be used to illuminate possible interactions between the brain, behaviour, genetics and environmental exposures.

Impact of research: 
This research may impact the scientific field by enhancing our understanding of behavioural and biological pathology associated with autism and the potential links to other psychiatric conditions such as psychosis. This research may encourage further research into biomarkers and interventions for autism and overlapping conditions. This work may also inform clinicians and the general public about the presence of autism-related traits in subclinical populations.
Date proposal received: 
Friday, 18 December, 2020
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Mental health, Medical imaging, Statistical methods, Birth outcomes, Development, Equipment - MRI, Environment - enviromental exposure, pollution, Epigenetics, Genetics

B3687 - Sensation-Seeking Related DNA Methylation and the Development of Delinquency A Longitudinal Epigenome-Wide Study - 12/01/2021

B number: 
B3687
Principal applicant name: 
Edward Dylan Barker | King's College London (United Kingdom)
Co-applicants: 
Jacintha Tieskens | PhD-student
Title of project: 
Sensation-Seeking Related DNA Methylation and the Development of Delinquency: A Longitudinal Epigenome-Wide Study
Proposal summary: 

Experiences of childhood maltreatment is suggested as an important risk factor for the development of delinquent behaviour. Heightened sensation-seeking is related to the development of delinquency. Moreover, sensation-seeking, or biological correlates of sensation-seeking, are suggested as factors linking childhood maltreatment to delinquency. More specifically, it is hypothesized that epigenetic correlates of sensation-seeking might function as a mechanism for translating environmental signals into biological changes that may subsequently lead to maladaptive behavior development. In this study we will try to identify the epigenetic correlates of sensation-seeking in children and investigate whether these epigenetic correlates are influenced by earlier experiences of childhood maltreatment and may impact subsequent development of delinquency in early adolescence.

Impact of research: 
Important information will become available on possible mechanisms of how adverse social experiences may become ‘under the skin’ and lead to maladaptive behavioural outcomes, such as delinquency. In addition, the role of sensation-seeking in the development of delinquency will become clearer and this information may help prevention programs to focus on important precursors of delinquent behaviour instead of intervene when delinquent symptoms are already present.
Date proposal received: 
Thursday, 17 December, 2020
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Epigenetics

B3695 - Genetic risk for Alzheimers disease and the metabolome across the life course - 12/01/2021

B number: 
B3695
Principal applicant name: 
Emma Anderson | University of Bristol
Co-applicants: 
Ms Hannah Compton, Dr Joshua Bell
Title of project: 
Genetic risk for Alzheimer’s disease and the metabolome across the life course
Proposal summary: 
Impact of research: 
informing other scientists about potential mechanisms of genetic risk for alzheimer's disease
Date proposal received: 
Tuesday, 5 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Epidemiology, Alzheimer's disease, Statistical methods, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B3679 - A Negative Control Analysis Investigating Maternal Smoking Alcohol consumption and BMI on Molar-Incisor Hypomineralisation - 12/01/2021

B number: 
B3679
Principal applicant name: 
Tom Dudding | University Hospitals Bristol (honorary: University of Bristol) (United Kingdom)
Co-applicants: 
Qui-Yi Lim, Kurt Taylor, Professor Deborah Lawlor
Title of project: 
A Negative Control Analysis Investigating Maternal Smoking, Alcohol consumption and BMI on Molar-Incisor Hypomineralisation.
Proposal summary: 

Molar-incisor Hypomineralisation (MIH) is a tooth condition specifically affecting the enamel (outer layer of the tooth) of one or more of the child’s first adult molars (back teeth) and in some cases the incisors (front teeth). MIH affected teeth appear discoloured, and vary in presentation; cream, yellow or brown. Teeth are commonly very sensitive, painful and in severe cases crumbly. Furthermore, affected teeth often have a poor prognosis and are more susceptible to dental decay meaning the teeth are often extracted before adulthood. It is usually diagnosed when the adult molars and incisors erupt in the mouth at around 6-7 years of age. In some cases, it can also affect the primary teeth, which is known as hypominersalised second primary molars (HSPM) and is seen around 2-3 years of age.

MIH has a high prevalence; approximately 13.1% globally (95% CI 11.8-14.5%) and 15.9% in the UK (95% CI 14.5-17.1%). The literature suggests MIH is caused by disturbances during tooth development. This is influenced by genetics and environmental factors, particularly during pregnancy, time of birth and in the first few years of life. Some of the environmental factors investigated include breastfeeding, environmental toxins (dioxins and Bisphenol A), problems occurring at birth and childhood illnesses. However, the literature concludes that the aetiology of MIH is unclear. Currently, there is little research on maternal factors and MIH, particularly the common environmental risk factors; maternal smoking (7 studies – the most recent suggesting a significant association) and alcohol consumption (2 studies), both in which the strength of evidence is weak and conflicting. Furthermore, much of the research conducted is retrospective and therefore prone common biases such as recall bias. There is a need for high-quality prospective studies. Other studies suggest that maternal smoking and alcohol consumption are associated with offspring HSPM. The embryological development of the second primary molars and first permanent molars are similar, and therefore may share the same environmental influences.

We propose to conduct a prospective study looking at the association between common maternal pregnancy characteristics and MIH. These include maternal smoking, alcohol consumption and body mass index (BMI). We will assess for the presence of residual confounding by including a negative parental exposure control. This involves comparing the confounder adjusted associations of maternal pregnancy exposures with the offspring outcome of interest to similarly adjusted associations of the same characteristics (negative controls) in the father. Similarly, we will use offspring dental trauma as a negative control outcome. Triangulating results from conventional multivariable regression, negative exposure controls and negative outcome controls provides scope to improve causal understanding.

Impact of research: 
Our results should help to improve our understanding on whether maternal smoking, alcohol consumption and BMI have an effect on MIH. This may help to provide accurate and non-stigmatised public health advice about maternal exposures and the dental health of children. As MIH affected teeth have been reported to have very poor prognosis and accounts for a significant proportion of childhood decay, diagnosing and intervening as early as possible can affect outcomes significantly. Understanding the risk factors may help to identify at-risk children and provide early intervention.
Date proposal received: 
Tuesday, 5 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Dentistry, Molar-incisor Hypomineralisation, Negative control, BMI, Development, Dental

B3697 - Investigating predictors of risk behaviours in adolescence and early adulthood - 12/01/2021

B number: 
B3697
Principal applicant name: 
Hannah Sallis | MRC IEU
Co-applicants: 
Prof. Marcus Munafo, Dr Zoe Reed, Dr Caroline Wright, Miss Agnes Kessling, Miss Ruby Richards
Title of project: 
Investigating predictors of risk behaviours in adolescence and early adulthood
Proposal summary: 

Identifying and understanding predictors of risky behaviour can help to inform prevention and intervention strategies for related outcomes. For example, alcohol consumption may have an influence on risky sexual behaviour, understanding this relationship could inform prevention and interventions for sexually transmitted diseases, unplanned pregnancies, abortions, and general sexual health. Another risk factor is for subsequent risk behaviours is adverse childhood experiences (ACEs). Individuals with histories of multiple ACEs are found to be more likely to engage in risk behaviours such as smoking, excessive drinking, risky sexual behaviour, illicit drug use and suicidal behaviour than those without.
This project will use longitudinal data from the ALSPAC study to identify predictors of risk behaviours in adolescence and early adulthood.

Impact of research: 
Date proposal received: 
Monday, 11 January, 2021
Date proposal approved: 
Tuesday, 12 January, 2021
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Sexually transmitted diseases, chlamydia, gonorrhoea, Statistical methods, Childhood - childcare, childhood adversity, Offspring, Statistical methods

B3689 - An individual participant data meta-analysis examining the associations between mode of delivery and respiratory outcomes - 06/01/2021

B number: 
B3689
Principal applicant name: 
Theodosia Salika | MRC LEU, University of Southampton (United Kingdom)
Co-applicants: 
Professor Hazel Inskip
Title of project: 
An individual participant data meta-analysis examining the associations between mode of delivery and respiratory outcomes.
Proposal summary: 

Systematic reviews and meta-analyses using aggregate data have indicated an increased risk of childhood asthma for women undergoing caesarean section, but the results were subject to moderate heterogeneity, potential residual confounding and publication bias1-4. We aim to use the EU child cohort network to re-examine the associations with different types of delivery using IPD MA to produce a more reliable pooled meta-analytic estimate. Potential mediators such as respiratory tract infections and allergic sensitization will be examined for the associations between different types of mode of delivery and asthma.

Impact of research: 
This will provide information about the association between mode of delivery and childhood asthma to inform policy about caesarean section usage.
Date proposal received: 
Friday, 18 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B3686 - LifeCycle How do early years risk factors mediate inequalities in child mental health and cognitive development - 06/01/2021

B number: 
B3686
Principal applicant name: 
David Taylor-Robinson | University of Copenhagen; University of Liverpool
Co-applicants: 
Dr Daniela Schlüter, Dr Katrine Strandberg-Larsen, Dr Angela Pinot de Moira, Anne-Marie Nybo Andersen, Gabriella Melis
Title of project: 
LifeCycle: How do early years risk factors mediate inequalities in child mental health and cognitive development?
Proposal summary: 

Reducing inequalities in child mental health is a public health priority, yet the pathways that link social conditions to mental health outcomes in the early years are unclear. Few studies have compared the social distribution and prevalence of mental health problems across countries, or have compared pathways to any inequalities. Understanding these pathways is critical in order to guide public policy to improve child health and reduce inequalities. In Life Cycle cohort families we aim to assess how early years risk factors mediate the relationship between childhood SECs and subsequent inequalities in child mental health and cognitive development.

Impact of research: 
Reducing inequalities in child mental health is a public health priority, yet the pathways that link social conditions to mental health outcomes in the early years are unclear. Few studies have compared the social distribution and prevalence of mental health problems across countries, or have compared pathways to any inequalities. Understanding these pathways is critical in order to guide public policy to improve child health and reduce inequalities.
Date proposal received: 
Tuesday, 5 January, 2021
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Epidemiology

B3694 - Epigenome-wide association study of handedness - 06/01/2021

B number: 
B3694
Principal applicant name: 
Matthew Suderman | University of Bristol (United Kingdom)
Co-applicants: 
Veronika Odintsova
Title of project: 
Epigenome-wide association study of handedness
Proposal summary: 

Hand preference is only weakly determined by genetics. Consequently, environment likely plays a role by modifying the expression of certain genes during early development. In this study, we will ask to what extent DNA methylation, a well-known regulator of genes, is associated with hand preference in ALSPAC children and their parents beyond known genetic associations.

Impact of research: 
Improved understanding of the relationship between DNA methylation and handedness.
Date proposal received: 
Monday, 4 January, 2021
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Developmental biology, hand preference, Microarrays, Development, Epigenetics, Handedness

B3690 - Epigenetic prediction of pubertal timing - 06/01/2021

B number: 
B3690
Principal applicant name: 
Peter Tanksley | University of Texas at Austin (United States)
Co-applicants: 
Kathryn Paige Harden, PhD, Elliot Tucker-Drob, PhD, Laurel Raffington, PhD
Title of project: 
Epigenetic prediction of pubertal timing
Proposal summary: 

Puberty is a time of sweeping biological and social change. Boys and girls who experience early and/or rapid puberty are at elevated risk for psychiatric and physical health problems, including substance use disorders, suicide, polycystic ovary syndrome (in females), and cardiovascular disease. Psychiatric disorders like major depressive disorder also become much more prevalent at puberty and may impede cognitive skill development . Considering the many negative implications of departures from the normal pubertal development, understanding the genetic and environmental regulators of puberty has become a topic of increasing urgency. Our research aims to identify specific and potentially modifiable environmental factors that influence pubertal timing and examine its association with children’s cognitive development and mental health, and we view genetic and epigenetic data as essential tools for accomplishing that goal.

Scientific progress on understanding genetic influences and epigenetic changes (including DNA methylation) at puberty has moved slowly. Previous studies looking at changes in DNA methylation across puberty have been conducted in very small samples; nevertheless, this previous work support the potential to develop an epigenetic clock for pubertal age, analogous to epigenetic clocks that exist for aging. However, generating a clock that is highly accurate and robust requires longitudinal DNA methylation data spanning the pubertal transition. We will substantially improve the rigor and reproducibility of previous research on the epigenetics of pubertal age by using a discovery sample that is substantially better-powered (the Texas Twin project) and by replicating results in an independent sample (ALSPAC). We can then examine potential environmental (e.g., family socioeconomic background) and genetic predictors (e.g., polygenic scores of reproductive phenotypes) of our epigenetic clock for pubertal age, as well as the cognitive and mental health sequelae of advanced epigenetic pubertal age.

Impact of research: 
We believe this research will have impact in at least three ways. First, this research will create a better understanding of how environments, genetics, and epigenetics work together to shape pubertal development. Second, this research will provide a biomarker of pubertal age that will be a useful resource for future research. Third, this research will contribute to a better understand of the mechanisms underlying and modifying adverse experiences around the pubertal transition.
Date proposal received: 
Friday, 18 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Puberty

B3692 - Pregnancy complications menopausal symptoms and cardiovascular health - 06/01/2021

B number: 
B3692
Principal applicant name: 
Abigail Fraser | MRC IEU (United Kingdom)
Co-applicants: 
Title of project: 
Pregnancy complications, menopausal symptoms and cardiovascular health
Proposal summary: 

The link between women's reproductive and cardiovascular health is increasingly recognised. Some, but not all studies have shown that women who experience night sweats and/or hot flushes as part of the menopausal transition are more likely to have heart disease. We also know that women who have complications during pregnancy are at greater risk of heart disease later in life. Here we would like to investigate the associations between all of pregnancy complications, menopausal symptoms and cardiovascular health in a general population of women, the ALSPAC mothers. We will also use genetics data to examine whether genetic risk for for more adverse cardiovascular health are associated with pregnancy complications and/or vasomotor symptoms.

Impact of research: 
This study will improve our understanding of the nature of the relationship between pregnancy complications, VMMS and women's cardiovascular health.
Date proposal received: 
Tuesday, 22 December, 2020
Date proposal approved: 
Wednesday, 6 January, 2021
Keywords: 
Epidemiology, DNA sequencing, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cardiovascular, Genetic epidemiology, Mothers - maternal age, menopause, obstetrics

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