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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B3983 - The effects of maternal antenatal fatigue and stress on maternal and offspring mental health - 17/02/2022

B number: 
B3983
Principal applicant name: 
Tiina Riekki | University of Oulu, Finland (Finland)
Co-applicants: 
MD, PhD Juha Veijola, MSc Martta Kerkelä, MD, PhD Golam Khandaker
Title of project: 
The effects of maternal antenatal fatigue and stress on maternal and offspring mental health
Proposal summary: 

Maternal fatigue is common during pregnancy, but knowledge on predisposing factors is scarce, and research on the effects of maternal antenatal fatigue on maternal mental health and offspring mental health is lacking. We will study factors associated with maternal fatigue in a cross-sectional setting. Secondly, we will study if maternal fatigue associates with mental health in the offspring. In both settings ALSPAC will be used as replication sample for findings in the Northern Finland Birth Cohort 1986 (NFBC1986).

Impact of research: 
The findings of this unique and novel research project will provide new knowledge for clinical professionals and researchers on maternal antenatal fatigue and its' effects on the mental health in the offspring. If maternal antenatal fatigue is significantly associated with adverse maternal or offspring mental health outcomes, systematically identifying women at risk for fatigue before conception or in early pregnancy, in order to prevent or manage maternal fatigue, could eventually reduce psychiatric illness in population level.
Date proposal received: 
Friday, 28 January, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Fatigue, Mental health, Psychiatry, Stress

B3993 - Use of a polygenic risk score to stratify for treatment for extreme short stature - 17/02/2022

B number: 
B3993
Principal applicant name: 
Brent Richards | Five Prime Sciences Incorporated (Canada)
Co-applicants: 
Dr. Vince Forgetta, Dr. Jasmine Chong, Thomas Harrison, Dr. Yossi Farjoun
Title of project: 
Use of a polygenic risk score to stratify for treatment for extreme short stature
Proposal summary: 

Children with idiopathic short stature (ISS) are defined by height below 2 standard deviations (SD) of the mean for age and sex without any endocrine, metabolic or other disease explaining the short stature. Recently the US Food and Drug Administration has approved Vosoritide for individuals with extreme short stature which is caused by a single gene mutation.

However, there are causes of extreme short stature that are not due a single gene mutation. These include polygenic predisposition to disease. We have recently generated a polygenic risk score that can reliably predict adult height, and this was tested in the ALSPAC cohort. We hypothesize that children who are extremely short due to a polygenic cause may also benefit from Vosoritide therapy.

Therefore, we posit that a polygenic risk score can help to identify children at extreme short stature. It could also help to predict if Vosoritide therapy could be helpful, by assessing if genetic changes in the biological pathway that is influenced by Vosoritide influences height. Last, we can use this polygenic risk score to better understand if extreme short stature is associated with other diseases and medically-relevant traits.

Impact of research: 
We hope that our research program will help children overcome the negative medical consequences of extreme short stature due to a polygenic cause. We feel that this is promising because Vosoritide therapy is already approved for monogenic causes of extreme short stature.
Date proposal received: 
Monday, 7 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Bone disorders - arthritis, osteoporosis, Congenital abnormalities, Gastrointestinal, Hypertension, Mental health, Obesity, Respiratory - asthma, GWAS, Proteomics, Blood pressure, BMI, Cardiovascular, Genetic epidemiology

B3974 - The intergenerational transmission of religiosity - 14/02/2022

B number: 
B3974
Principal applicant name: 
Jonathan Jong | Coventry University (United Kingdom)
Co-applicants: 
Peter C. Hill, Daryl R. Van Tongeren, Don E. Davis, Joshua N. Hook, Adam Baimel, Carol Joinson, Isaac Halstead
Title of project: 
The intergenerational transmission of religiosity
Proposal summary: 

Children often—but not always—retain the religious identities, beliefs, and practices of their parents. This project aims to find patterns in what we call “intergenerational religious transmission”, with a particular focus on parents’ religious denominations, their own religious beliefs and behaviours, their intentions to raise their children in their religious traditions, and their children’s religious beliefs, behaviours, and attitudes during childhood. A secondary purpose is to test the “religious residue” hypothesis over time, which contends that religious deidentifiers still maintain aspects (i.e., residue) of their former religious identities.

Impact of research: 
It will provide much-needed longitudinal evidence to the literature on intergenerational religious transmission that currently mostly relies on multi-cohort, cross-sectional, and/or retrospective studies. In addition, it will offer insights into the developmental trajectory of religious change, which is a significant contribution to existing research.
Date proposal received: 
Wednesday, 9 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Social Science, Religiosity, Statistical methods, Psychology - personality

B4001 - The role of parental religiosity in offspring mental health - 14/02/2022

B number: 
B4001
Principal applicant name: 
Isaac Halstead | Bristol university (United Kingdom)
Co-applicants: 
Carol Joinson, Jon Heron
Title of project: 
The role of parental religiosity in offspring mental health
Proposal summary: 

There is limited evidence for the role of parental religious beliefs in offspring mental health, with the existing literature predominantly concerned with American samples, and a limited number of mental health outcomes. This project seeks to examine the role of parental religious beliefs, and how they may predict offspring mental health in childhood and adolescence. This will be done using a broad range of mental health measures, and possible confounding, mediating, or moderating variables.

Impact of research: 
This research will provide an insight into the role of parental religious beliefs in their children's mental health over time.
Date proposal received: 
Monday, 14 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Social Science, Mental health, Statistical methods, Social science

B3997 - Investigating links between regulatory T cell depletion and mood and psychotic symptoms - 14/02/2022

B number: 
B3997
Principal applicant name: 
Evie Stergiakouli | MRC IEU
Co-applicants: 
Miss Freya Shepherd, Dr William Davies
Title of project: 
Investigating links between regulatory T cell depletion and mood and psychotic symptoms
Proposal summary: 

Immune dysregulation is thought to be involved in psychiatric disorders, including psychotic and mood disorders (1). Regulatory T cells (Tregs), an important component of the immune system, may have a role when investigating the causes of disorders such as anxiety, depression and psychosis. For example reduced number of Tregs have been found in individuals with disorders including schizophrenia, postpartum psychosis and major depression (2-4). However, the role of immune dysregulation in mood and psychotic symptoms in the general population has not been investigated. Through ALSPAC, we will investigate whether Treg sensitive genes are more common in individuals who have reported mood and psychotic symptoms, including post-partum depression. In combination with follow up experiments, this project will help us understand whether immune dysregulation is a risk factor for mood and psychotic symptoms.

Impact of research: 
This translational project will use genetic approaches to identify specific human behavioural and psychiatric phenotypes associated with known Treg-sensitive genes. As such, it will enhance our understanding of how Treg levels may impact upon psychiatric disorder risk, and inform future work in rodent models investigating the neurobiological/immunological basis of any observed associations. Polygenic scores may also feed into predictive models for psychiatric risk. It is the intention that this work may be published in peer-reviewed journals and at appropriate national and international conferences; it will be of interest to the psychiatric, genetics, neuroscience, and immunology scientific and medical communities.
Date proposal received: 
Wednesday, 9 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, GWAS, Genetic epidemiology, Genetics

B3932 - Examining the latent structure of ALSPAC RSBB variables - 14/02/2022

B number: 
B3932
Principal applicant name: 
Isaac Halstead | Bristol Medical School (Oxfordshire)
Co-applicants: 
Jean Golding, Carol Joinson, Jon Heron
Title of project: 
Examining the latent structure of ALSPAC RSBB variables
Proposal summary: 

There are a variety of ways to measure religious beliefs. However, there is evidence that some commonly used measures of religiosity function poorly for atheist and spiritual individuals. In the ALSPAC there are a several measures of religiosity based upon pre-existing scales, such as the Duke University Religion Index (DUREL) and the Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS). The aim of the current study is to examine the latent structure of the items taken from these scales, for use in ALSPAC, and to explore whether these items are measurement invariant across religious, atheist and spiritual individuals. This will provide an insight into the way religiosity is measured in ALSPAC and inform future scale construction using these items.

Impact of research: 
By understanding the latent structure of the RSBB variables, we will be able to better estimate relationships between RSBB and a variety of outcomes. It will also validate their use in future papers.
Date proposal received: 
Thursday, 3 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Statistics/methodology

B3989 - Epigenetics of changing traits - individual EWAS linked to B3967 - 14/02/2022

B number: 
B3989
Principal applicant name: 
Andrew Simpkin | NUI, Galway (Ireland)
Co-applicants: 
Vikram Jambunathan
Title of project: 
Epigenetics of changing traits - individual EWAS linked to B3967
Proposal summary: 

The last decade has seen a dramatic improvement in our understanding of how our genes affect our height, body mass index (BMI), mental health, cancer risk, and many other traits. This has been facilitated by technological developments which allow us to measure a persons’ epigenetic data accurately and economically. Almost all epigenetic studies investigate traits collected at a single timepoint (e.g. adult height), and the epigenetic sites associated with these traits are then found using an epigenome wide association study (EWAS). However, some traits such as BMI change over time, and the epigenetics of these repeatedly measured traits remain poorly understood. This project will apply new approaches for epigenetic analysis of longitudinal traits - in particular BMI measured repeatedly from birth to adulthood and depressive symptoms from later childhood through adolescence.

Impact of research: 
This research has major potential. The epigenetic analysis of changing/longitudinal phenotypes has yet to be developed, while methods are available in the GWAS context. Therefore, strong results in this study could lead to discoveries across a range of changing phenotypes, as longitudinal and epigenetic data continue to be collected more regularly. With ALSPAC/ARIES a leading cohort for epigenetic data analysis, these developments will open lots of pathways for research using data from Bristol.
Date proposal received: 
Wednesday, 2 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Obesity, Statistical methods, Development, Epigenetics, Growth, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3988 - Exploring the suicidal drive hypothesis for psychosis - 14/02/2022

B number: 
B3988
Principal applicant name: 
Jamie Murphy | Ulster University (Northern Ireland)
Co-applicants: 
Professor Mark Shevlin, Dr. Philip Hyland, Dr. Sarah Butter
Title of project: 
Exploring the suicidal drive hypothesis for psychosis
Proposal summary: 

A recent suicidal drive hypothesis posits that psychotic experiences (PEs) may serve to externalize internally generated and self-directed threat (i.e., self-injurious/suicidal thought/behavior [SITB]) in order to optimize survival. Preliminary investigations have attempted to demonstrate that such internal threat can both precede and inform PEs. To date findings derived from analyses of cross-sectional epidemiological data, national prospective cohort/service use data, and, prospective twin cohort data have indicated that SITB is indeed predictive of PEs. This study seeks to explore the hypothesis further.

Impact of research: 
If findings were to support the proposed hypotheses they would have the potential to revolutionize how we look at suicidality in the context of psychosis (and vice versa).
Date proposal received: 
Wednesday, 2 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B3787 - The effect of timing and cessation of maternal smoking upon the DNA methylation score - 14/02/2022

B number: 
B3787
Principal applicant name: 
Rae-Chi Huang | Lifecycle (Australia)
Co-applicants: 
Jennie Carson, Dr Phil Melton, Dr Sylvain Sebert, Kimberley Burrows
Title of project: 
The effect of timing and cessation of maternal smoking upon the DNA methylation score
Proposal summary: 

The smoking score was developed in the Raine Study (partner: University of Western Australia/Telethon Kids Institute, Perth, Western Australia) and the Northern Finland Birth Cohorts 1986 and 1966 (partner: University of Oulu, Oulu, Finland). For the score development, DNA methylation data measured with the Illumina HumanMethylation450 BeadChip array was utilized, together with a binary variable, indicating if the study participant’s mother was smoking during pregnancy.

Our hypothesis is that the smoking score captures and quantifies latent information on early life exposure. We also hypothesize that it quantifies the persistent changes that occur systemically in the offspring with maternal smoking exposure in utero.

Impact of research: 
The intention of this research is to identify which trimester of smoking during pregnancy has the greatest impact on the child's smoking score.
Date proposal received: 
Monday, 31 January, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Statistical methods, Epigenetics

B3984 - Long-Term Occupational Implications of Preschool Gender-Related Play Behaviour - 14/02/2022

B number: 
B3984
Principal applicant name: 
Karson T. F. Kung | University of Hong Kong (China)
Co-applicants: 
Title of project: 
Long-Term Occupational Implications of Preschool Gender-Related Play Behaviour
Proposal summary: 

Globally, there are substantial gender gaps in occupations. Men are overrepresented in leadership and managerial positions, as well as in science, technology, engineering, and mathematics (STEM) fields, whereas women are overrepresented in administrative and assistant positions, as well as in education and social welfare fields. Similar gender differences are evident in the UK, where men represented 66% of parliament members in 2019 (UK Parliament, 2020), 67% of leadership board members across the top 350 companies listed on the London Stock Exchange in 2020 (FTSE Women Leaders, 2021), and 73% of the STEM workforce in 2019 (British Science Association, 2020), whereas women represented 72% of school teachers, 86% of nurses, and 92% of secretaries in 2018 (UK Office for National Statistics, 2018).

The developmental approach is underused in existing high-level strategies designed to tackle the gender gaps, although the roots of these gaps can be traced back to early childhood. Crucially, aspects of childhood play show some of the most substantial behavioural gender differences in human development. It has been proposed that male- and female-typical play are qualitatively different and differentially contribute to the development of personal characteristics and gender-related socio-cognitive processes (Kung, 2022). Recently, using ALSPAC data, Kung (2021) has provided the first evidence that preschool gender-related play behaviour longitudinally predicts gender-related occupational interests in adolescence. Nonetheless, it remains unknown whether childhood play contributes to actual occupational choices in adulthood.

This proposed study will test the relationship between preschool gender-related play behaviour and gender-related occupations in adulthood.

KEY REFERENCES

Kung, K. T. F. (2021). Preschool gender-typed play behavior predicts adolescent gender-typed occupational interests: A 10-year longitudinal study. Archives of Sexual Behavior, 50, 843–851.

Kung, K. T. F. (2022). Gender differences in children’s play. In P. K. Smith and C. H. Hart (Eds.), The Wiley-Blackwell handbook of childhood social development (3rd ed.). Chichester, UK: Wiley-Blackwell.

Impact of research: 
Globally, gender segregation in different occupations can be commonly observed. These substantial gender differences in work contribute to the worldwide gender pay gap and lifelong income inequality. The roots of these differences can be traced back to childhood. A more advanced understanding of the relevant mechanisms in early development is needed, so that the developmental roots of the gender gaps can be tackled properly. In the long run, a more gender-balanced workforce across different sectors can reduce income inequality and ensure more diverse perspectives and approaches in different industries. Previously, Kung (2021) found that preschool gender-related play can predict adolescent gender-related occupational interests. The current study will extend Kung (2021) and test if there is a link between preschool gender-related play and gender-related occupations in adulthood. If there is link between the two, parents and educators may facilitate more diverse occupational outcomes amongst boys and girls by encouraging them to engage in a wider range of play activities.
Date proposal received: 
Sunday, 30 January, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Developmental Psychology and Gender Studies, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Development, Psychology - personality, Sex differences

B3987 - Validation of the Our Future Health genotyping assay - 25/04/2022

B number: 
B3987
Principal applicant name: 
Benjamin Cairns | Our Future Health (United Kingdom)
Co-applicants: 
Dr Ryan Arathimos, Dr Michael Cook
Title of project: 
Validation of the Our Future Health genotyping assay
Proposal summary: 

Our Future Health will collect information from up to 5 million volunteers from across the UK to create one of the most detailed pictures we’ve ever had of people’s health. Researchers will be able to use this information to discover more effective ways to prevent, detect and treat diseases. As part of the programme, genetic information will be extracted from blood samples collected from the volunteers, using a new genetic test which will give information on over 600,000 genetic variants (DNA which may vary from person to person). Before it can be used, however, the test will require preliminary accuracy checks and other comparisons on a collection of samples where the correct genetic information is already known. We propose to conduct these checks on a set of 1800 samples from the ALSPAC cohort, which have established cell-lines for DNA extraction and whole genome sequence information as part of the UK10K programme. These samples will be tested by the supplier of the genetic test, and the results sent to Our Future Health for comparison against the reference genetic information. For any genetic variants that do not meet our pre-specified level of accuracy, this part of the test will be re-designed by the supplier and the assessments repeated. This work will help to ensure that the Our Future Health genetic tests are as accurate as possible, and through the Our Future Health programme will contribute to research to prevent, detect and treat disease for decades to come.

Impact of research: 
This performance assessment study of the genotyping assay is vital to the Our Future Health research programme and to the application of the genotyping assay to up to 5 million participant samples. Our Future Health aims to speed up the discovery of new methods of early disease detection, and the evaluation of new diagnostic tools, to help identify and treat diseases early when outcomes are usually better. Building this large resource will facilitate a new generation of discovery and translational research that will advance the development and testing of early diagnostic technologies and preventive (or ‘personalised precision health’) interventions.
Date proposal received: 
Tuesday, 1 February, 2022
Date proposal approved: 
Monday, 7 February, 2022
Keywords: 
Genetics, No specific diseases/conditions - assay validation study to support future large-scale research across a range of diseases., Microarrays, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Cohort studies - attrition, bias, participant engagement, ethics, Genetics, Genomics, Statistical methods

B3981 - Parental age and offspring DNA methylation - 07/02/2022

B number: 
B3981
Principal applicant name: 
Giulia Mancano | University of Bristol (United Kingdom)
Co-applicants: 
Ms Fernanda Morales Berstein , Dr Edwina H Yeung, Dr Rebecca Richmond, Dr Gemma Sharp
Title of project: 
Parental age and offspring DNA methylation
Proposal summary: 

Advanced parental age has been associated with adverse offspring health outcomes, but the biological mechanisms underlying these associations remain unclear. Research suggests that epigenetics may play a role, especially since advanced parental age has been associated with lower levels of offspring DNA methylation, which in turn, have been associated with adverse offspring outcomes. Nevertheless, the association between advanced parental age and epigenetics has only been explored in two studies with relatively small sample sizes. Larger epigenome-wide association studies are required to identify more CpG sites and improve our understanding of epigenetic mechanisms underlying the observed associations between advanced parental age and adverse offspring health outcomes.

References:
1. Adkins RM, Thomas F, Tylavsky FA, Krushkal J. Parental ages and levels of DNA methylation in the newborn are correlated. BMC Med Genet. 2011;12:47.
2. Markunas CA, Wilcox AJ, Xu Z, et al. Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. PLoS One. 2016;11(7):e0156361.
3. Pinheiro RL, Areia AL, Mota Pinto A, Donato H. Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis. Acta Med Port. 2019;32(3):219-226.
4. Ryer EJ, Ronning KE, Erdman R, et al. The potential role of DNA methylation in abdominal aortic aneurysms. Int J Mol Sci. 2015;16(5):11259-11275.

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 advanced parental age and adverse offspring health outcomes.
Date proposal received: 
Wednesday, 26 January, 2022
Date proposal approved: 
Monday, 7 February, 2022
Keywords: 
Epigenetics, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., EWAS, Epigenetics, Fathers, Mothers - maternal age, menopause, obstetrics, Offspring

B3978 - Genome-wide association study of bone mineral density in ALSPAC children and mothers - 04/02/2022

B number: 
B3978
Principal applicant name: 
Monika Frysz | University of Bristol (United Kingdom)
Co-applicants: 
Prof Jon Tobias, Dr Ahmed Elhakeem, John Kemp
Title of project: 
Genome-wide association study of bone mineral density in ALSPAC children and mothers
Proposal summary: 

Osteoporosis is a common age-related condition with a strong genetic component. Osteoporotic fractures significantly contribute to disease burden and costs. Whilst a number of genes responsible have been identified, many gene variants each contribute to the disease but each with subtle effect.
Previous GEnetic Factors for OSteoporosis Consortium (GEFOS) study identified a number of BMD-related loci using a genome-wide association study (GWAS). As part of this collaboration, an ongoing meta-analysis of four DXA-derived BMD traits is being conducted. Cohorts previously involved as well as new and updated cohorts are being invited to take part in this effort.

Impact of research: 
Publication in a high impact journal
Date proposal received: 
Friday, 21 January, 2022
Date proposal approved: 
Friday, 4 February, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Bone disorders - arthritis, osteoporosis, GWAS, Genome wide association study

B3986 - Early Environmental quality and life-course mental health effects - Equal Life - 15/02/2022

B number: 
B3986
Principal applicant name: 
Anna Hansell | University of Leicester, Centre for Environmental Health and Sustainability (United Kingdom)
Co-applicants: 
Miss Yingxin Chen, Professor John Gulliver, Dr Arzu Arat, Professor Charlotte Clark, Professor Jenny Selander, Dr Calvin Jephcote, Professor Irene van Kamp, Dr Tatiana Alvares-Sanches, Ms Kathryn Adams
Title of project: 
Early Environmental quality and life-course mental health effects - Equal Life
Proposal summary: 

Air pollution, road transport noise and other environmental exposures in pregnancy and early life may affect many aspects of a child's development and have long-term effects tracking into adult life. However, there are few studies on the impact of very early life exposures to environmental pollution. This study will focus on effects of environmental exposures in early life on mental health and cognition in childhood. The analyses will form part of a large European study with over 30 participating institutions. The answers will help develop environmental policies to protect children's health and development.

Impact of research: 
The findings of this project would provide new knowledge that will inform UK and European guidelines and policy for the provision of healthy educational environments for children, having relevance for the design and placement of new schools and roads, as well as for air pollution and noise abatement schemes for schools exposed to high levels of noise. 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: 
Monday, 31 January, 2022
Date proposal approved: 
Tuesday, 1 February, 2022
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Learning difficulty, Mental health, Speech/language problem, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Intelligence - memory, Linkage, Speech and language

B3985 - Uncovering novel early life risk factors and molecular markers for cancer prevention - 09/02/2022

B number: 
B3985
Principal applicant name: 
Rebecca Richmond | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdom)
Co-applicants: 
Ms Fernanda Morales Berstein, Dr Tom Richardson, Dr Maria Carolina Borges, Professor Caroline Relton, Professor George Davey Smith
Title of project: 
Uncovering novel early life risk factors and molecular markers for cancer prevention
Proposal summary: 

Cancer is a leading cause of morbidity and mortality worldwide. Its burden is expected to increase in the coming years as populations age and increase their exposure to unhealthy lifestyle factors. Most research on cancer aetiology has been conducted in adult populations. This has led to the identification of well-established risk factors in adulthood, such as smoking and obesity. Nevertheless, it is still unclear whether cancer risk may be influenced by early life exposures. Furthermore, the mechanisms by which early life exposures may influence cancer risk have not been fully elucidated. They possibly involve inflammation, changes in the microbiome, metabolism, insulin resistance, hormonal factors and epigenetic modifications. Therefore, the aim of this project will be to identify novel early life risk factors and molecular markers for the prevention of cancer.

Impact of research: 
This study will contribute to our understanding of causal mechanisms linking early life exposures and the incidence of different types of cancer.
Date proposal received: 
Monday, 31 January, 2022
Date proposal approved: 
Monday, 31 January, 2022
Keywords: 
Epidemiology, Cancer, GWAS, Metabolomics, Microarrays, Proteomics, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Genetic epidemiology, Genome wide association study, Hormones - cortisol, IGF, thyroid, Mendelian randomisation, Metabolic - metabolism

B3976 - Is the Bike Drawing test a useful indicator of brain-related visual function in ALSPAC participants - 31/01/2022

B number: 
B3976
Principal applicant name: 
Cathy Williams | University of Bristol (United Kingdom)
Co-applicants: 
Harry Adams
Title of project: 
Is the Bike Drawing test a useful indicator of brain-related visual function in ALSPAC participants
Proposal summary: 

I am PI for an exsting project (B3770) which uses ALSPAC data to explore whether a seletion of candidate genes (known to influence the brain's ability to respond to injury) are related to the presence or absence of brain-related vision problems.

In this add-on project, a medical student will examine some additional data from ALSPAC, to see whether the results of a task (the Bike Drawing task; BD) the ALSPAC children carried out at age 11 are in agreement with the results of the brain-related vision tests already requested and in use in B3770. The BD task is an adaptation (for ALSPAC) of a standard neuropsychology assesment called the Rey Osterrieth Complex Figure Test (ROCFT), which assesses visuoconstructive skills and visual memory. This project will therefore be a learning exercise for the student and will provide useful preliminary data as to whether the BD task may be useful in clinical paediatric ophthalmology practice.

Impact of research: 
This project will provide the medical student with a good introduction to basic epidemiological and statistcal concepts, using a world-famous resource and the opportunity to submit a paper to a scientific journal. The results will indicate whether this BD task may have a place in clinical practice as an indicator of brain-related visual function as applied to a practical task. This will be of interest to clinical and patient groupd that are interested in cerebral visual impairment (CVI).
Date proposal received: 
Wednesday, 19 January, 2022
Date proposal approved: 
Monday, 31 January, 2022
Keywords: 
Epidemiology, Cognitive impairment, Learning difficulty, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Visual impairment, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3977 - Estimate the causal effect of maternal smoking during pregnancy on offsprings birth weight using ALSPAC data - 04/02/2022

B number: 
B3977
Principal applicant name: 
Qijun Li | University of Michigan (United States)
Co-applicants: 
Prof Xu Shi, Prof Eric Tchetgen Tchetgen, Prof George Davey Smith, Mr. Wes Spiller, Dr. Eleanor Sanderson, Prof Kate Tilling, Prof Wang Miao
Title of project: 
Estimate the causal effect of maternal smoking during pregnancy on offsprings’ birth weight using ALSPAC data
Proposal summary: 

Numerous studies have shed light on the effects of maternal smoking during pregnancy on the offsprings’ health outcomes. In particular, maternal smoking during pregnancy was found to be associated with lower offspring birthweight. Previous studies normally address confounding by adjusting for maternal age, socioeconomic status, breastfeeding and offspring gender. However, concerns about unmeasured confounding biases due to the mother’s lifestyle, the households’ socioeconomic status, and mother’s genotypes still remain.

The negative control method is a recently popularized approach that utilizes measured covariates as proxies of unmeasured confounders, in order to detect, reduce and correct for confounding bias. This method may help eliminate the confounding bias when studying the causal effect of maternal smoking on child birth weight. For example, paternal alcohol consumption during the mother’s pregnancy can serve as a potential negative control variable since it’s a proxy of the household’s socioeconomic status but shouldn’t directly affect the offspring’s birth weight. Therefore, any observed association between paternal alcohol consumption and the child’s birth weight is likely a result of confounding bias. Other negative control variables may include negative control exposures (NCEs) such as mother’s smoking behavior after giving birth, and negative control outcomes (NCOs) such as the child’s injuries since age 9.

In this project, we will utilize multiple negative control variables to obtain a more accurate estimate of the causal effect of maternal smoking during pregnancy on infants’ birthweight with the ALSPAC data.

Impact of research: 
Conferences presentations and combination with other analyses to generate paper in high-impact journal.
Date proposal received: 
Wednesday, 19 January, 2022
Date proposal approved: 
Monday, 31 January, 2022
Keywords: 
Statistics/methodology, Statistical methods, Birth outcomes

B3982 - Maternal metabolic risk factors and prognosticators for offspring affected by congenital heart disease - 07/02/2022

B number: 
B3982
Principal applicant name: 
Massimo Caputo | University of Bristol
Co-applicants: 
Dr Stuart Mires, Dr Clare Skerritt
Title of project: 
Maternal metabolic risk factors and prognosticators for offspring affected by congenital heart disease.
Proposal summary: 

Congenital anomalies complicate over 2% of births, with congenital heart disease (CHD) the most common accounting for approximately one third. However, understanding of potential causes is limited, with only 20% related to known genetic, chromosomal or teratogenic factors. Greater knowledge of maternal risk factors and causative mechanisms is essential. Assessing the maternal metabolome offers an opportunity to achieve these goals. Metabolomics describes the study of small molecules and substances created by the processes of the body. It reflects how the body functions and is influenced by genetics, our environment and other factors such as health conditions and pregnancy. This project will perform large scale metabolomic analysis utilising the Children-OMACp, ALSPAC and Surgical-PEARL cohort studies based in the South-West of England. Firstly, case control study will compare metabolomic profiles of non-pregnant mothers of children with CHD to controls with no congenital anomaly. Further study will then compare metabolomic profiles in pregnant mothers of fetuses with CHD and controls with no congenital anomaly. This research aims to elucidate potential maternal metabolic risk factors and causative pathways for fetal CHD. It will also allow us to greater understand the role the fetus has in influencing maternal metabolomic profiles in pregnancies complicated by CHD. This can be compared to underlying maternal metabolic variation that could represent a causative pathway for fetal CHD. This understanding could revolutionise care for women before and during pregnancy. Furthermore, it offers an exciting opportunity for primary prevention of CHD.

Impact of research: 
It is clear that our understanding of maternal causal risk factors and mechanisms for fetal CHD is limited. The assessment of the maternal metabolome provides the opportunity to change this. This project will perform metabolomic assessment of both non-pregnant and pregnant mothers of children with CHD to identify potentially causative metabolic profiles and pathways. This will reduce the physical and psychological burden on children, families and societies as well as benefiting the NHS. Furthermore, it will improve opportunities for pre-conception counselling, optimising peri-conceptual care. The ultimate goal through greater understanding of causative mechanisms and pathways would be to develop pre- and peri- conceptual management strategies and treatments that could act in the primary prevention of CHD.
Date proposal received: 
Wednesday, 26 January, 2022
Date proposal approved: 
Monday, 31 January, 2022
Keywords: 
Epidemiology, Congenital abnormalities, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Mass spectrometry, Metabolomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Cardiovascular, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism

B3956 - Investigating the effects on happiness life satisfaction and meaning in life following the transition to parenthood - 27/01/2022

B number: 
B3956
Principal applicant name: 
Claire Haworth | University of Bristol (UK)
Co-applicants: 
Ms. Megan Hamilton, Ms. Nina Di Cara
Title of project: 
Investigating the effects on happiness, life satisfaction, and meaning in life, following the transition to parenthood
Proposal summary: 

The project will investigate the impact that the transition to parenthood has on wellbeing. In particular, the project will focus on understanding how becoming a parent impacts individuals’ happiness, life satisfaction and meaning in life using a longitudinal design.
Research investigating the impact of parenthood on wellbeing produces mixed findings. Some findings indicate that parenthood is associated with detrimental effects on wellbeing (Stanca, 2012), whilst others have suggested that parenthood is associated with improved aspects of wellbeing (Nelson et al., 2013). However, the research investigating the effects of parenthood on wellbeing is difficult to summarise, due to the varying definitions of wellbeing that are used within the literature and the different means of operationalising the term. For example, studies have measured wellbeing by examining symptoms of depression, alcohol abuse, happiness, life satisfaction and frequency of positive and negative emotions. Therefore, this study aims to look at how parenthood effects different aspects of wellbeing individually as there may be differential effects of parenthood on happiness, life satisfaction, and meaning in life. Prior studies have found that parents have higher levels of meaning in life than non-parents (Nelson et al., 2013). However, there are more mixed findings regarding happiness and life satisfaction (Umberson & Gove, 1989). Therefore, the findings regarding the relationship between parenthood and wellbeing do not represent one construct and making concluding statements about parenthood and wellbeing would fail to acknowledge the discrepancies among how wellbeing has been measured and defined.
Previous research has suggested that the relationship between parenthood and wellbeing differs depending on gender, relationship status and financial strain on the parent. It has been reported that mothers experience poorer wellbeing in comparison to fathers (Nelson et al., 2019). Parents who are married may have better wellbeing in comparison to single parents because of the proposed benefits such as division of labour in the home and for parenting tasks (Cunningham & Knoester, 2007). Stanca (2012) also reported that parenthood negatively impacts life satisfaction due to a lack of financial satisfaction and increased financial strain associated with parenthood. Whether the individual is a first-time parent may also be important to investigate because experiences of parenting might not match prior expectations with consequences for mental health in new parents (Harwood et al., 2007).

Impact of research: 
The likely impact of this research is that it could allow a clearer insight into how parenthood impacts happiness, life satisfaction, and meaning in life, as distinct aspects of wellbeing. It is hoped that investigating these as distinct aspects of wellbeing will avoid the problem of making generalised conclusions about parenthood and its effects on wellbeing, which obscures the nuances of this relationship. Instead, the research could indicate whether parenthood effects these outcomes in the same way or in different ways. The consequences of poor mental health among parents and the effects it has on their children have been investigated. It has been proposed that for parents suffering with poor mental health, there is an increased risk of negative impacts to their children’s cognitive, emotional, and behavioural functioning and development (Stein et al., 2014). Therefore, investigating the effects of parenthood on wellbeing outcomes is likely to be important because it could help to identify whether aspects of wellbeing are negatively impacted. This could then be used to inform whether investigation is needed into finding interventions to improve the impacted aspect of wellbeing and could be used to investigate how parental wellbeing influences children.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Thursday, 27 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Parenting, Psychology - personality, Social science

B3957 - Investigating the impact of anxiety on coping strategies during a pandemic - 27/01/2022

B number: 
B3957
Principal applicant name: 
Claire Haworth | University of Bristol (UK)
Co-applicants: 
Ms. Amalita Vacher, Ms. Nina Di Cara
Title of project: 
Investigating the impact of anxiety on coping strategies during a pandemic
Proposal summary: 

The unprecedented national lockdowns in 2020/21 in response to the COVID-19 pandemic gave many reasons for people to experience increased levels of stress and anxiety driven by potential factors such as fear of illness or death, social isolation, losing jobs and loss of autonomy. To manage the negative experiences of situations like this, people commonly engage in coping strategies to reduce their perceived stress. Potential coping strategies include engaging in exercise, changes in eating, drinking and smoking patterns, social interaction and engagement with news, media reports and conversation related to the pandemic.
We aim to investigate whether there is a relationship between the level of anxiety experienced early in the first UK lockdown and participants subsequent coping behaviours. Did those with higher levels of anxiety at the start of lockdown engage in different coping strategies to those less anxious? Furthermore, how does engaging in certain coping strategies impact levels of anxiety later in the pandemic? Through this further investigation, inferences can be made about how well certain coping strategies work for individuals with different levels of anxiety.

Impact of research: 
If the patterns of coping can be understood for different levels of anxiety then interventions can be adapted accordingly for those with high, medium and low anxiety levels. There is a need to address the protective coping mechanisms, employed during times of negative affect created by national lockdowns, so that appropriate policies and programs can be developed, whilst mitigating maladaptive strategies. Understanding who is at risk of engaging in maladaptive coping mechanisms will allow for future interventions to be made for those most vulnerable. Not only will this research elucidate patterns of coping during pandemics but also provide a foundation for future research into coping strategies for more general experiences of negative affect.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Thursday, 27 January, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality, Social science

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