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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B4222 - Early-life vitamin D status and lung function in childhood and adolescence observational and mendelian randomization analyses - 19/12/2022

B number: 
B4222
Principal applicant name: 
Raquel Granell | MRC Integrative Epidemiology Unit (IEU)
Co-applicants: 
Dr Maribel Casas Sanahuja, Júlia Sangüesa Boix
Title of project: 
Early-life vitamin D status and lung function in childhood and adolescence: observational and mendelian randomization analyses.
Proposal summary: 

In this study we aim to analyse whether or not vitamin D levels during pregnancy influence lung development and, consequently, the occurrence of asthma and lung function performance in childhood and adolescence. To analyse these associations, we will use two methodologies. First, we will look at whether or not vitamin D levels measured in blood during pregnancy are associated with the onset of asthma and lung function parameters at 8-9 years and 15-16 years in the ALSPAC cohort. Since this association may be influenced by many confounding factors such as lifestyle, socio-economic status, the season of the year when the blood was obtained, we will use Mendelian Randomisation to overcome this limitation. We will analyse whether or not genetic variants that predispose to having low levels of vitamin D are associated with a greater predisposition to having asthma and poorer lung function in childhood and adolescence. We will use data from 4 different European cohorts and one Australian cohort and, after doing all the analysis separately, we will collect the results and do a meta-analysis using all data.

Impact of research: 
High impact publication
Date proposal received: 
Tuesday, 13 December, 2022
Date proposal approved: 
Monday, 19 December, 2022
Keywords: 
Genetics, Respiratory - asthma

B4225 - Polygenic risk score of asthma COPD and lung function and association with lung function outcomes - 19/12/2022

B number: 
B4225
Principal applicant name: 
Raquel Granell | MRC Integrative Epidemiology Unit
Co-applicants: 
Prof Erik Melén, Dr Natalia Hernandez-Pacheco , Dr Christina Dardani
Title of project: 
Polygenic risk score of asthma, COPD and lung function, and association with lung function outcomes
Proposal summary: 

Genetic variants associated with lung function and susceptibility to airway diseases such as asthma or COPD might be implicated in lung function development from birth to adulthood. Here, we would be able to assess whether very low and low lung function trajectories are primarily associated with asthma, COPD, or lung function genetics, and related mechanisms. Disentangling the genetic factors derived from asthma, COPD, and lung function studies underlying the trajectory of poor pulmonary capacity across the lifespan could contribute to identifying new lung function biomarkers and to early prevent the development of chronic airway diseases. By using a PRS approach, we anticipate having better power to evaluate asthma and COPD mechanisms in lung function trajectories compared to a standard GWAS approach.

Impact of research: 
Date proposal received: 
Wednesday, 14 December, 2022
Date proposal approved: 
Monday, 19 December, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B4226 - Religiosity Confounders Mediators and Bidirectional Causality - 19/12/2022

B number: 
B4226
Principal applicant name: 
Dan Major-Smith | Population Health Sciences, University of Bristol
Co-applicants: 
Prof Jean Golding, Prof Kate Northstone
Title of project: 
Religiosity: Confounders, Mediators and Bidirectional Causality
Proposal summary: 

Key to causal inference from observational data is adequate adjustment for confounders (i.e., factors which cause both the exposure and outcome). However, knowing whether a variable is a confounder (requiring statistical adjustment) or a mediator (i.e., a variable caused by the exposure which in turn causes the outcome; not requiring statistical adjustment) is often difficult to establish with certainty and often relies upon potentially-debatable assumptions. By making use of the repeated data collected by ALSPAC - both in terms of religiosity and data on other covariates which may be plausible confounders and/or mediators - it is possible to make reasonable inferences as to whether religiosity causes the covariate, the covariate causes religiosity, or indeed whether there is bidirectional causation (i.e., religiosity causes the covariate and the covariate also causes religiosity). If data permit adjustment for baseline confounders, prior exposure and prior outcomes, then it may be possible to infer causality using longitudinal observational data (VanderWeele 2021; VanderWeele et al., 2016). We intend to apply these methods in ALSPAC to explore potential bidirectional causation between religiosity and a range of covariates to better understand these patterns and to help inform future work using these data.

References:
VanderWeele, T. J. (2021). Can sophisticated study designs with regression analyses of observational data provide causal inferences?. JAMA psychiatry, 78(3), 244-246.
VanderWeele, T. J., Jackson, J. W., & Li, S. (2016). Causal inference and longitudinal data: a case study of religion and mental health. Social psychiatry and psychiatric epidemiology, 51(11), 1457-1466.

Impact of research: 
We hope this research will provide a better understanding of the causes and consequences of religion, and help inform future work in this area using ALSPAC's religion data.
Date proposal received: 
Thursday, 15 December, 2022
Date proposal approved: 
Monday, 19 December, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Statistical methods

B4184 - Gender-based violence over the life course using cohort data from the Avon Longitudinal Study of Parents and Children - 19/12/2022

B number: 
B4184
Principal applicant name: 
Emmanuela Gakidou | Institute for Health Metrics and Evaluation, University of Washington (USA)
Co-applicants: 
Caroline Stein, Jack Cagney, Mariam Khalil, Cory N Spencer, Molly E Herbert, Alejandra Arrieta, Julia Hon
Title of project: 
Gender-based violence over the life course using cohort data from the Avon Longitudinal Study of Parents and Children
Proposal summary: 

Gender-based violence (GBV) is a global public health problem. It is present in all ages and socioeconomic statuses. However, a better understanding of GBV over the life course and the long-term impact of violence exposure on health outcomes is still required. Therefore, the objective of this project is to evaluate and understand gender-based violence over the life course and the many factors involved in this violation of women's and children's human rights. To do this, we will use the ALSPAC cohort study, which include among others a range of both parent and self-reported questions related to gender-based violence, such as data on physical, psychological, and sexual violence occurring during different periods of life. Using this data, it will be possible to estimate (i) cumulative exposure to GBV; (ii) the intergenerational exposure to GBV; (ii) the differences in GBV considering gender, age, education, and income level; and (iv) the impact of violence exposure on health outcomes.

Impact of research: 
This research can impact future public health policies, providing a longitudinal perspective on gender-based violence. The results from this analysis can inform decision-makers on creating public health policies and implementing interventions in the community to prevent and stop gender-based violence in our society.
Date proposal received: 
Thursday, 8 December, 2022
Date proposal approved: 
Monday, 19 December, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, Statistical methods, Childhood - childcare, childhood adversity, Gender-based violence, physical violence, sexual violence, psychological/emotional violence, life-course (multiple time series), perpetrator, location of violence

B4212 - Improving treatment of menopausal symptoms by using genomics to understand aetiology - 22/12/2022

B number: 
B4212
Principal applicant name: 
Anna Murray | University of Exeter (UK)
Co-applicants: 
Dr Kate Ruth, Dr Julia Prague, Professor Abigail Fraser, Professor Martha Hickey
Title of project: 
Improving treatment of menopausal symptoms by using genomics to understand aetiology
Proposal summary: 

Menopausal symptoms affect around 70% of women as they go through the menopause, but we don't know very much about what causes the various symptoms. It is not clear how different symptoms might be linked and who is at risk of developing them. We will use genomics to find the causes of a range of menopausal symptoms, including; hot flushes, sleep disturbance, mood changes and sexual dysfunction. We will develop a questionnaire to distribute to study participants to collect information about their symptoms and combine this with genomic data previously collected.

Impact of research: 
We anticipate that our genomic studies will identify novel potential drug targets to treat the often debilitating symptoms of the menopause transition.
Date proposal received: 
Wednesday, 7 December, 2022
Date proposal approved: 
Wednesday, 14 December, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Menopause, Gene mapping, GWAS, Statistical methods, Endocrine - endocrine disrupters, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Mothers - maternal age, menopause, obstetrics, Whole genome sequencing

B4211 - Genetic architecture of feeling loved in childhood GWAS and genetic correlations - 14/12/2022

B number: 
B4211
Principal applicant name: 
Hannah Sallis | Bristol Medical School, University of Bristol
Co-applicants: 
Ms Amy Campbell, Professor Marcus Munafò, Professor Rebecca Pearson
Title of project: 
Genetic architecture of feeling loved in childhood: GWAS and genetic correlations
Proposal summary: 

Research has shown that adults who look back on their childhood and say that they had a positive relationship with their parents, or felt loved by their parents, have better mental health. Indeed, these emotional memories can be more important for mental health than memories of specific behaviours that parents engaged in. However, we don’t know how the relationship between feeling loved in childhood and mental health actually comes about.
In this study, we will firstly look at how genetics relates to people saying they felt loved in childhood. People who took part in a large research study answered a question about whether they felt loved in childhood and provided a blood sample, so that we can look at their genetics. Genetic material (DNA) is made up of millions of tiny units called base pairs. At each base pair, a person can have one of two alleles. We will look at whether the allele that a person has at each base pair increases or decreases their likelihood of reporting that they felt loved in childhood. We will then look at whether there are similarities in how genetics contributes to feeling loved in childhood and depression, anxiety, and wellbeing.
This will help us to understand some of the reasons people are more or less likely to say they felt loved in childhood. It can also provide a better understanding of how feeling loved in childhood relates to mental health. All of this is important for how we understand the causes of mental health problems.

Impact of research: 
This research will contribute to our understanding of the aetiology of mental health disorders, particularly depression and anxiety. It will also provide important information for future research - using the results of this study we can generate a genetic risk score for feeling loved in childhood, allowing future research to use this as a proxy for the phenotype in causal instrumental variable analyses.
Date proposal received: 
Wednesday, 7 December, 2022
Date proposal approved: 
Wednesday, 14 December, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, GWAS, Parenting

B4213 - Does religious practice moderate the association between adverse childhood experiences and weight trajectories in adult women - 09/01/2023

B number: 
B4213
Principal applicant name: 
Jimmy Morgan | Population Health Sciences, University of Bristol
Co-applicants: 
Professor Jean Golding, Professor Deborah Lycett, Cain Clark
Title of project: 
Does religious practice moderate the association between adverse childhood experiences and weight trajectories in adult women?
Proposal summary: 

We aim to explore the associations between adverse childhood events (ACEs) and weight trajectory (diet change, alcohol consumption, and change in physical activity) amongst the G0 Mothers in ALSPAC. Also investigating whether religious beliefs and behaviours (and changes thereof) moderate this relationship and whether depression score mediates this relationship. In these analyses we will adjust for relevant confounders such as demographic characteristics, smoking status, and age.

Impact of research: 
Further the resources available on the impact in adulthood of adverse childhood events and targets for intervention development.
Date proposal received: 
Friday, 9 December, 2022
Date proposal approved: 
Wednesday, 14 December, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Eating disorders - anorexia, bulimia, Mental health, Obesity, Statistical methods, BMI, Childhood - childcare, childhood adversity, Mothers - maternal age, menopause, obstetrics, Nutrition - breast feeding, diet, Physical - activity, fitness, function, Statistical methods

B4214 - The joint effect of blood lead and vitamin D on preterm birth in the Avon Longitudinal Study of Parents and Children - 20/12/2022

B number: 
B4214
Principal applicant name: 
Mandy Fisher | Health Canada (Canada)
Co-applicants: 
Dr. Bruce Lanphear, Dr. Caroline Taylor , Ms. Leonora Marro, Dr. Ahmed Elhakeem, Dr. Beth Potter, Dr. Jillian Ashley-Martin, Dr. Michael Borghese, Mr. Ryan Iverson
Title of project: 
The joint effect of blood lead and vitamin D on preterm birth in the Avon Longitudinal Study of Parents and Children
Proposal summary: 

Preterm birth, the leading cause of death in children younger than five, is a risk factor for brain-based disorders, asthma, and ischemic heart disease. Lead is a toxic chemical and a known risk factor for preterm birth. Vitamin D may modify this relationship due to its probable antioxidant properties.

In a recent pan-Canadian study examining 1,851 live births from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort, prenatal exposure to low concentrations of lead increased the risk of preterm birth and spontaneous preterm birth, and the risks were stronger among mothers with insufficient vitamin D levels, suggesting that they might be more susceptible to the toxic effects of lead. However, average blood lead concentrations among mothers were low among a modest sample size, and replication of these findings is warranted.

We aim to estimate the joint association of blood lead and vitamin D with preterm birth the Avon Longitudinal Cohort of Parents and Children.

Impact of research: 
Preterm birth is the leading cause of death in children younger than five and a risk factor for brain-based disorders, asthma, and ischemic heart disease. In Canada, approximately 7 to 8% of births are preterm (Abitbol and Rodriguez 2012; Sonnenschein-Van Der Voort et al. 2014; Sutton and Darmstadt 2013) This approach will confirm whether the association between lead and preterm birth is stronger in women with insufficient 25OHD concentrations, which suggests that a considerable proportion of preterm births can be prevented by adequate vitamin D supplementation. Widespread exposures to subtle risk factors can have substantial impacts on the prevalence of preterm birth. The implications of our study extend beyond preterm birth. Lead is a risk factor for preeclampsia and ischemic heart disease (Lanphear et al. 2018; Poropat et al. 2018). UB investigators found that low vitamin D was not a significant risk factor for preeclampsia in the ALSPAC cohort, but it was a risk factor for pre-eclampsia in their meta-analysis (Hyppönen et al. 2014). Examining the joint effect of blood lead and vitamin D may clarify these results. The joint effects of blood lead, air pollution and vitamin D on cardiometabolic health could also be explored in the ALSPAC cohort. These types of studies raise intriguing questions about the joint effect of diet and toxic chemicals, especially for low-income communities burdened by air pollution, toxic chemicals, and inadequate nutrition. References: Abitbol, Carolyn L., and Maria M. Rodriguez. 2012. “The Long-Term Renal and Cardiovascular Consequences of Prematurity.” Nature Reviews Nephrology. Hyppönen, Elina et al. 2014. “Vitamin D and Pre-Eclampsia: Original Data, Systematic Review and Meta-Analysis.” Annals of Nutrition and Metabolism 63(4). Lanphear, Bruce P et al. 2018. “Low-Level Lead Exposure and Mortality in US Adults: A Population-Based Cohort Study.” The Lancet Public Health 3(4). Poropat, Arthur E et al. 2018. “Blood Lead and Preeclampsia: A Meta-Analysis and Review of Implications.” Environmental Research 160. Sonnenschein-Van Der Voort, Agnes M.M. et al. 2014. “Preterm Birth, Infant Weight Gain, and Childhood Asthma Risk: A Meta-Analysis of 147,000 European Children.” Journal of Allergy and Clinical Immunology. Sutton, Perri S., and Gary L. Darmstadt. 2013. “Preterm Birth and Neurodevelopment: A Review of Outcomes and Recommendations for Early Identification and Cost-Effective Interventions.” Journal of Tropical Pediatrics.
Date proposal received: 
Friday, 9 December, 2022
Date proposal approved: 
Wednesday, 14 December, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Environment - enviromental exposure, pollution

B4221 - Identifying clusters of COVID-19 and Long Covid symptoms - 13/12/2022

B number: 
B4221
Principal applicant name: 
Charlotte James | UoB
Co-applicants: 
Title of project: 
Identifying clusters of COVID-19 and Long Covid symptoms
Proposal summary: 

Information can be obtained from ALSPAC (B number folder) or the UK LLC on request

Impact of research: 
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
Date proposal received: 
Tuesday, 13 December, 2022
Date proposal approved: 
Tuesday, 13 December, 2022
Keywords: 
Epidemiology, Infection

B4220 - UKLLC Mental health and COVID-19 vaccine outcomes - 13/12/2022

B number: 
B4220
Principal applicant name: 
Ru Jia | University of Nottingham
Co-applicants: 
Title of project: 
UKLLC: Mental health and COVID-19 vaccine outcomes
Proposal summary: 

Information can be obtained from ALSPAC (B number folder) or the UK LLC on request

Impact of research: 
Information can be obtained from ALSPAC (B number folder) or the UK LLC on request
Date proposal received: 
Tuesday, 13 December, 2022
Date proposal approved: 
Tuesday, 13 December, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition

B4210 - Cross-ancestry Epigenome Wide Association study EWAS of objectively measured physical activity in pregnancy - 14/12/2022

B number: 
B4210
Principal applicant name: 
Nancy McBride | MRC IEU (United Kingdom)
Co-applicants: 
Dr Paul Yousefi, Professor Deborah Lawlor, Dr Christine Sommer, Nicolas Fragoso Bargas
Title of project: 
Cross-ancestry Epigenome Wide Association study (EWAS) of objectively measured physical activity in pregnancy
Proposal summary: 

Physical activity (PA) during pregnancy reduces the risk of gestational diabetes mellitus (GDM) and excessive weight gain. DNA methylation (DNAm) - changes to DNA sequence but not the structure - is a potential molecular mechanism through which physical activity (PA) mediates the effects on the transcriptome. Original discovery analyses were run in a cohort from Norway (EPIPREG) and we want to replicate their findings to see if these CpG sites are associated with PA.

Impact of research: 
If we can replicate these findings, it may help understand more about DNA methylation (DNAm) as a potential molecular mechanism through which physical activity (PA) mediates the effects on the transcriptome. Whilst we can only look in ALSPAC adolescents and not pregnant women [because we don't have accelerometer data], these still have implications.
Date proposal received: 
Tuesday, 6 December, 2022
Date proposal approved: 
Thursday, 8 December, 2022
Keywords: 
Epidemiology, Obesity, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc.

B4209 - PhD project on Placentas adverse pregnancy outcomes and cardiometabolic health - 20/12/2022

B number: 
B4209
Principal applicant name: 
Abigail Fraser | Population Health Sciences, Bristol Medical School
Co-applicants: 
Genevieve Monaghan, Dr Carolina Borges, Dr Rachael Freathy
Title of project: 
PhD project on Placentas, adverse pregnancy outcomes, and cardiometabolic health
Proposal summary: 

The placenta is a crucial organ of mammalian pregnancy, connecting mother and fetus. Impaired placentation and placental development and function are associated with common pregnancy complications including preeclmapsia, fetal growth restriction and preterm delivery.
Here we will investigate associations between placental weight, dimensions and number of cotyledons and pregnancy outcomes as well as the long term health of both mothers and their offspring. We will also use the genetic data in order to identify determinants of the placental traits.

Impact of research: 
A better understanding of the role of the placenta and its determinants in pregnancy and lifelong health
Date proposal received: 
Wednesday, 30 November, 2022
Date proposal approved: 
Thursday, 8 December, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Cardiovascular, Mothers - maternal age, menopause, obstetrics, Nutrition - breast feeding, diet, Offspring

B4207 - School lunch choices at age 13 years in persistent picky eaters in a longitudinal birth cohort study - 23/11/2022

B number: 
B4207
Principal applicant name: 
Dr Caroline Taylor | University of Bristol (United Kingdom)
Co-applicants: 
Abigail, Dr Pauline Emmett
Title of project: 
School lunch choices at age 13 years in persistent picky eaters in a longitudinal birth cohort study
Proposal summary: 

The aim of the project is to look at foods and food group choices in school meals and snacks by children aged 13 years who were persistent picky eaters in the early years. The data were collected via questionnaires that the children completed themselves. Children with persistent picky eating habits during their early years have already been identified. Their choices will be compared with those of children who were not picky eaters.

Impact of research: 
Greater insight into long-term effects of early picky eating and transitions to self-directed eating in teenage years
Date proposal received: 
Wednesday, 23 November, 2022
Date proposal approved: 
Wednesday, 23 November, 2022
Keywords: 
Nutrition, Child development, Statistical methods, Nutrition - breast feeding, diet

B4206 - Intergenerational Cohort Consortium ICC - 28/11/2022

B number: 
B4206
Principal applicant name: 
Craig Olsson | Deakin University Australia (Australia)
Co-applicants: 
Dr Chris Greenwood
Title of project: 
Intergenerational Cohort Consortium (ICC)
Proposal summary: 

The primary objective of the Intergenerational Cohort Consortium (ICC) is to maximise the value of some of the most mature multi-generational data to complete a series of analyses (and associated publications) providing new insights into intergenerational pathways that connect parental life histories, from infancy to parenthood, to offspring psychosocial development decades later. Key outcomes include parent psychosocial adjustment and caregiving behaviour, and offspring psychosocial development. The aim is to identify modifiable factors that act to break intergenerational cycles of disadvantage and strengthen families from one generation to the next.

Planned analyses will specifically address questions about intergenerational transmission that cannot be answered in any one cohort. These include questions about the reproducibility and generalisability of findings reported from single studies; questions about intergenerational effects of low prevalence exposures (e.g., histories of illicit drug use and self-harm), and; questions which require contributions from different cohorts to provide a more complete picture of development processes (e.g., piecing together positive pathways from childhood to young adulthood).

Further information can be found in our ICC profile paper:
https://doi.org/10.1332/175795920X15792720930280

The ICC is a consortium within our broader LifeCourse initiative:
https://lifecourse.melbournechildrens.com/
https://doi.org/10.1093/ije/dyac086

Impact of research: 
Our program of research aims to identify major intergenerational pathways important to social and emotional development. Findings from the research have already been cited in policy documents around the world, including WHO, UN and NICE. Findings have also been directly translated into a new Australian Comprehensive Monitoring system that seeks to map intergenerational cycles of risk at the population level, across 8 interconnected surveys spanning early childhood to young adulthood (https://doi.org/10.1332/175795921X16599509057666)
Date proposal received: 
Wednesday, 23 November, 2022
Date proposal approved: 
Wednesday, 23 November, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Ageing

B4205 - The intergenerational links between PRS of ADHD in mothers and childhood maltreatment in their children - 06/12/2022

B number: 
B4205
Principal applicant name: 
Helen Minnis | supervisor (UK)
Co-applicants: 
Evi Bali
Title of project: 
The intergenerational links between PRS of ADHD in mothers and childhood maltreatment in their children
Proposal summary: 

Childhood maltreatment has a profound impact on both the short- and long-term wellbeing of children. Specifically, children with autism and those with attention deficit/hyperactivity disorder have a higher risk to experience maltreatment than those with typical development. However, the reasons why this is happening, are unclear. Two studies will be conducted. The first study will investigate the relationship between childhood maltreatment and ADHD. Studies support an association between ADHD and maltreatment: Children with ADHD have higher risk of experience maltreatment than those without ADHD, as well as people who suffered childhood maltreatment have high levels of ADHD symptoms and diagnosis. Also, parental ADHD and/or experience of maltreatment could influence the strength of this association. So, we will define and analyse how genetic and social factors affect the association between ADHD and childhood maltreatment, and then how this could be developed through generations. Having assessed and display the association between ADHD and childhood maltreatment, the second study will go a step forward searching the experience of physical abuse and harsh parenting in children with ADHD and children with autism. We will conduct a comparison between children with ADHD and children with autism trying to understand how the different traits of each condition may affect different the risk of physical abuse and harsh parenting.

Impact of research: 
The immediate impact of this research will likely be at least 2 peer reviewed publication in a general journal (i.e. PLOS Medicine). We aim to present and discuss results in a way that is robust enough for academics but is accessible and relevant to clinicians and public health practitioners, ultimately encouraging greater attention for the association between ADHD and childhood adverse experience, like maltreatment.
Date proposal received: 
Monday, 21 November, 2022
Date proposal approved: 
Tuesday, 22 November, 2022
Keywords: 
Epidemiology, Developmental disorders - autism, Mental health, GWAS, Statistical methods, Childhood - childcare, childhood adversity, Genetic epidemiology, Parenting

B4203 - UKDS Non-Communicable Disease Risk Factor Collaboration NCD-RisC - 22/11/2022

B number: 
B4203
Principal applicant name: 
Rachel Heap | Imperial College London (UK)
Co-applicants: 
Title of project: 
UKDS: Non-Communicable Disease Risk Factor Collaboration (NCD-RisC)
Proposal summary: 

Please see associated paperwork in relevant B number folder

Impact of research: 
Date proposal received: 
Monday, 21 November, 2022
Date proposal approved: 
Tuesday, 22 November, 2022
Keywords: 
Epidemiology

B4204 - Intelligence and Religion - 22/11/2022

B number: 
B4204
Principal applicant name: 
Dan Major-Smith | Population Health Sciences, University of Bristol
Co-applicants: 
Dr Isaac Halstead, Prof Jean Golding, Dr Jonathan Jong
Title of project: 
Intelligence and Religion
Proposal summary: 

Religion is an important suite of beliefs and behaviours, yet the factors which cause religious beliefs and behaviours are still largely unknown. One such factor believed to shape religion is intelligence, with previous meta-analyses suggesting a negative association between measures of intelligence and religious belief (Zuckerman et al., 2020). However, the majority of this previous research has been cross-sectional and focused predominantly on American undergraduates, meaning results may be biased by confounding and/or not generalisable to the wider population. We therefore need longitudinal data from population-based studies with repeated religiosity and intelligence data to assess whether these associations may be causal in a more representative population. Enter ALSPAC.

References:
Zuckerman, M., Li, C., Lin, S. & Hall, J.A. (2020). The Negative Intelligence–Religiosity Relation: New and Confirming Evidence. Personal. Soc. Psychol. Bull., 46, 856–868.

Impact of research: 
Date proposal received: 
Monday, 21 November, 2022
Date proposal approved: 
Tuesday, 22 November, 2022
Keywords: 
Social Science, Statistical methods, Cognition - cognitive function

B4191 - EWAS of Green Spaces - LifeCycle - 22/11/2022

B number: 
B4191
Principal applicant name: 
Deborah A Lawlor | University of Bristol (UK)
Co-applicants: 
Genevieve Monghan, Dr Ahmed Elhakeem, Dr Kimberley Burrows
Title of project: 
'EWAS of Green Spaces - LifeCycle
Proposal summary: 

PLEASE NOTE ALL OF THE FOLLOWING SECTIONS ARE COPIED AND PASTED FROM A PREVIOUSLY APPROVED PROJECT THAT IS IDEANTICAL TO TO THIS - B3549. WE HAVE HAD TO SUBMIT AS A NEW PROJECT TO ACCOMODATE CHANGE TO THIS NOW BINE A PHS MINI PROJECT
The urban exposome (built environment, air pollution, road traffic noise, meteorological, natural space and road traffic) affects health outcomes. For instance, associations between increasing green space exposure and increased birth weight and decreased term low birth weight in 32,000 mother-child pairs have been previously reported (Nieuwenhuijsen et al. 2019).
Here we aim to investigate the epigenetic mechanisms that might mediate this association. We will evaluate the relationship between exposure to green spaces during pregnancy and offspring cord blood DNA methylation at over 450,000 methylation sites (CpG sites) across the genome. This project will contribute epigenome-wide association study summary results to a meta-analysis as part of an ongoing large consortium.

Impact of research: 
Understanding environmental determinants of variation in DNA mehylation across the life course.
Date proposal received: 
Thursday, 3 November, 2022
Date proposal approved: 
Tuesday, 22 November, 2022
Keywords: 
Epidemiology, Epigenetics Environmental Health, Epigenome Wide Analyses (EWAS); odd GWAS is in the list but EWAS is not, Epigenetics

B4196 - Epigenetic pathways to youth self-injurious thoughts and behaviours dissecting phenotypic heterogeneity and time course - 23/11/2022

B number: 
B4196
Principal applicant name: 
Gabriel Fries | University of Texas Health Science Center at Houston (USA)
Co-applicants: 
Salahudeen Mirza, Becky Mars, Sarah Watkins
Title of project: 
Epigenetic pathways to youth self-injurious thoughts and behaviours: dissecting phenotypic heterogeneity and time course
Proposal summary: 

Suicide is a leading cause of death among youth, but little is known about the associated risk factors. Growing recognition that the existing clinical and psychological measures do not predict suicidal behaviour very strongly has contributed to a focus on the genetic correlates and predictors of suicide risk. Although genotypes do not change across the lifespan, an epigenetic process known as DNA methylation is responsive to environmental experience and can modify the expression of certain genes. Although numerous investigations have cross-sectionally identified a role for DNA methylation changes in self-injurious thoughts and behaviours (such as suicide attempt, suicidal thoughts, and self-injury without suicidal intent), these studies have largely focused on adults. Given that development is associated with numerous biological, epigenetic, and psychosocial changes, there is a need to better identify specific DNA methylation risk factors in youth, rather than extrapolating from work in adults. In this project, we aim to conduct epigenome-wide association studies (case-control comparison of methylation at numerous locations in the genome) of suicide ideation; suicide attempt history; and self-injury without suicidal intent; in teenagers who are part of the Avon Longitudinal Study of Parents and Children. We will also be able to make use of methylation measurements taken in childhood and at birth to trace any methylation differences backward, in an attempt to understand when they might emerge. These findings will be essential to identifying youth-specific risk factors for suicide, and ultimately contribute to efforts to better inform risk assessment as well as biologically informed interventions.

Impact of research: 
This project will kickstart future projects investigating the biological underpinnings of youth SITBs. This will be the first epigenome wide association study of teenage suicide attempt, suicidal thoughts, or non suicidal self harm, and the first to employ longitudinal analyses using childhood or perinatal methylation. Further studies of functional genomics and longitudinal designs, including person-centered analyses, will be able to build on these foundational findings. Additionally, replication efforts in other cohorts will be welcome additions to the growing body of research in youth suicide biology. We anticipate that this will be a very well-received body of work.
Date proposal received: 
Wednesday, 9 November, 2022
Date proposal approved: 
Monday, 21 November, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Methylation wide association study, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Childhood - childcare, childhood adversity, Development, Epigenetics, Genetic epidemiology, Genetics, Genomics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B4197 - Early Life Factors and Childhood Metabolomic Profiles with Risk of Non-Alcoholic Fatty Liver Disease Fibrosis in Young Adults - 21/11/2022

B number: 
B4197
Principal applicant name: 
Stefani Tica | Washington University in Saint Louis School of Medicine (United States)
Co-applicants: 
Yin Cao, ScD, MPH, Phillip Tarr, MD, Xiaoyu Zong, MPH
Title of project: 
Early Life Factors and Childhood Metabolomic Profiles with Risk of Non-Alcoholic Fatty Liver Disease, Fibrosis in Young Adults
Proposal summary: 

Non-alcoholic liver disease (NAFLD) is the most common cause of liver disease among children and adults. NAFLD is a spectrum of disease which includes significant fat deposits in the liver, liver inflammation, and in some cases permanent scarring and cirrhosis. NAFLD is more common among individuals with obesity and metabolic syndrome. Current evidence suggests risk for NAFLD, obesity, and metabolic syndrome can be inherited and influenced by early life exposures. However, there is no framework for identifying who is at greatest risk for more severe liver disease (inflammation, scarring, cirrhosis). We aim to investigate whether development and severity of NAFLD in young adulthood is associated with blood markers of metabolism in childhood and parental factors.

Impact of research: 
We anticipate significant impact from the results of this investigation, as the developmental origins of NAFLD have been insufficiently explored in humans. This project will provide a novel insight into NAFLD development and progression. To our knowledge, this would be the first assessment of NAFLD risk using human maternal, paternal, and offspring data collected prospectively from the perinatal period into adulthood and is likely to robustly add to our current understanding of existing hypotheses. The findings and perspective from this study will be especially critical in identifying and prioritizing potential targets for public health intervention on this increasingly burdensome disease.
Date proposal received: 
Friday, 11 November, 2022
Date proposal approved: 
Monday, 21 November, 2022
Keywords: 
Clinical research/clinical practice, Gastrointestinal, Obesity, Computer simulations/modelling/algorithms, Metabolomics, NMR, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Liver function, Metabolic - metabolism, Nutrition - breast feeding, diet, Offspring, Statistical methods

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