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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B4003 - CAMCOG collection of cognitive data - 28/02/2022

B number: 
B4003
Principal applicant name: 
Ian Penton-Voak | UoB
Co-applicants: 
Dr Kate Northstone, Professor Nic Timpson
Title of project: 
CAMCOG: collection of cognitive data
Proposal summary: 

Cognitive data will be collected from both generations of ALSPAC using CamCog (Cambridge Cognition). This will be linked to the next ALSPAC COVID questionniare which is likely to go out just after Easter 2022.

Impact of research: 
Date proposal received: 
Tuesday, 15 February, 2022
Date proposal approved: 
Monday, 21 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Cognitive impairment, Cognition - cognitive function

B4002 - Pathway to psychosis among cannabis users - 28/02/2022

B number: 
B4002
Principal applicant name: 
Marta Di Forti | SGDP, KCL IoPPN (UK)
Co-applicants: 
Robin M Murray, Isabelle Austin-Zimmerman, Diego Quattrone , Giulia Trotta, Edoardo Spinazzola, Chloe Chung Yi Wong, Emma Dempster , Luis Alameda
Title of project: 
Pathway to psychosis among cannabis users
Proposal summary: 

Mendelian randomisation studies have not yet clarified the direction of causality between heavy cannabis use and Schizophrenia. Thus, while cannabis use remains the most preventable risk factor for psychotic disorders, it is still unclear what makes some heavy users more susceptible to develop clinical psychosis. This is a question of global relevance with the spreading of laws legalising cannabis use for medicinal and/or recreational purposes.

Recently, epigenetic processes that regulate where our DNA is expressed, have been implicated in both psychotic disorder and substance use. Indeed, genome wide DNA methylation (DNAm) studies (EWAS), which measures where the DNA is switched on or off, have become a tool to look at the biological effects of environmental exposures.
This proposal, nested within a larger MRC Senior Fellowship project, focuses on the development of a genome wide DNAm score associated with regular cannabis use, taking into account both genetic factors and other environmental exposures. These analyses will run in parallel to mouse model experiment of exposure to both THC and CBD (cannabidiol), the most studied ingredient of cannabis. Finally, we plan to examine overlaps in the effect of cannabis compounds on the brain of mice with the effect in human blood tissue, to begin to understand a) the neurobiology of psychosis in the context of heavy cannabis use and b) to build epigenetic and genetic scores that might help distinguish those cannabis users that come to no harm from those who develop a) sub-clinical psychotic experiences paranoia and b) frank clinical psychosis.

Impact of research: 
Our ambition is to develop, from the work on the genetic pathways and epigenetic scores associated with cannabis use, potential peripheral markers of cannabis associated psychosis-risk. These peripheral biomarkers could be integrated into screening tools to identify individuals at risk of developing psychosis outcome not only among recreational cannabis users but also among those prescribed medicinal cannabis use; the latter would allow them to receive closer monitoring and might increase confidence in the prescription of cannabis-based medication when indicated. The novelty of the comparative analyses of genetic-epigenetic data in the context of cannabis exposure from the human studies and from the mouse model experiment will 1) facilitate closer collaborations between the psychosis and neuroscience research communities and beyond to replicate and build on my findings; 2) inform Pharma companies of potential new drug targets and better understanding of how cannabidiol (CBD) and other potentially cannabinoids could be used in the treatment of cannabis-associated psychosis. All of these impacts are likely to become more important at a time of changes in cannabis legislation across the world.
Date proposal received: 
Monday, 14 February, 2022
Date proposal approved: 
Monday, 21 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, DNAm longitudinal profiling Genetics Pathway analyses, Statistical methods

B3917 - Gene-gene gene-enviroenment interaction and risk prediction of pediatric mental disorders multi-omics data analysis of ALSPAC - 17/02/2022

B number: 
B3917
Principal applicant name: 
Ruyang Zhang | Department of Biostatistics, Nanjing Medical University [https://gwxy.njmu.edu.cn/2017/0718/c8948a98532/page.htm] (China)
Co-applicants: 
Minjun Ji, Hao Chang, Jiajin Chen
Title of project: 
Gene-gene, gene-enviroenment interaction and risk prediction of pediatric mental disorders: multi-omics data analysis of ALSPAC
Proposal summary: 

Growing evidence shows that the environment exposure and molecular level of maternal conditions might affect mental health of children; However, the relationships remained elusive. In this project, we aimed to study the interaction effects between genes and genes (G×G), genes and environments (G×E), as well as environments and environments (E×E). Furthermore, by combining both main effects and interaction effects of genes and environments, we want to construct a prediction model for children depression.

Impact of research: 
The biomarkers of genes and environments (G×E) interactions might provide insight into mechanisms underpinning mental disorders and further substantially contribute to the accuracy of risk prediction model. The prediction model posses the capability to identify children at high risk of mental disorders, and aid physicians in making clinical decisions or guiding adjuvant therapy.
Date proposal received: 
Wednesday, 24 November, 2021
Date proposal approved: 
Thursday, 17 February, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Statistical methods, Childhood - childcare, childhood adversity

B3990 - Understanding developmental trajectories of risk and resilience amongst children who experienced adverse childhood experiences - 21/02/2022

B number: 
B3990
Principal applicant name: 
Lucy Bowes | University of Oxford
Co-applicants: 
Miss Athena Chow, Elise Sellars
Title of project: 
Understanding developmental trajectories of risk and resilience amongst children who experienced adverse childhood experiences
Proposal summary: 

Children who experience adverse childhood experiences (ACEs) are at greater risk for psychiatric disorders, chronic health diseases, and poor educational and social outcomes. Experiencing ACEs such as abuse, neglect or bullying in childhood increases vulnerability to poor developmental outcomes, yet not all children who experience such adversity go on to develop adjustment difficulties. Sources of resilience exist on multiple levels: individual characteristics including biological predisposition and psychological coping styles; physical, economic and social capital offered to children and caregivers; psychosocial interventions by mental health, social welfare, and education providers; and government policies that prioritise or neglect maltreated children. This project will integrate methods from social epidemiology and developmental psychology to understand the trajectories of risk and resilience amongst children who experienced ACEs, by using longitudinal analysis and advanced statistical methods to examine risk and protective factors at the individual, family, school and community level. Findings will inform intervention strategies and policies aimed at promoting resilience amongst vulnerable children.

Impact of research: 
In terms of academic impact, this project will advance overall understanding of the trajectories of risk and resilience across children’s development. In terms of policy impact, findings from this project will contribute to the evidence base and inform early interventions and policies (e.g., protective factors to be implemented during the early years) on how to improve services available for at-risk children and provide vulnerable families with sufficient support. In terms of clinical impact, findings from this project have the potential to inform clinical interventions (e.g., specific neurobiological mechanisms to be targeted) for the treatment of ACEs and subsequent mental illness.
Date proposal received: 
Thursday, 3 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Parenting, Siblings, Speech and language, Statistical methods

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

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

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

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.

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

B3998 - Development of anxiety and depression in young people explaining individual and cross-cohort differences in risk outcomes - 22/02/2022

B number: 
B3998
Principal applicant name: 
Stephan Collishaw | Wolfson Centre for Young People's Mental Health, Cardiff University (Uk)
Co-applicants: 
Dr Foteini Tseliou, Dr Jessica Armitage, Ms Egle Padaigaite, Dr Joanna Martin, Ms Charlotte Dennison, Prof Anita Thapar, Prof Frances Rice, Dr Vicky Powell, Dr Lucy Riglin, Prof Kate Tilling
Title of project: 
Development of anxiety and depression in young people: explaining individual and cross-cohort differences in risk & outcomes
Proposal summary: 

Adolescence is marked by rapid social and biological change and a sharp rise in the incidence of depression and some forms of anxiety. Youth anxiety and depression are typically foreshadowed by earlier childhood difficulties and exposure to multiple adversities; additionally, there are far-reaching consequences for outcomes in adulthood – for education and employment, relationships with others, and physical and mental health. Young people today are also more likely to experience anxiety and depression than previous generations.

There is substantial variability in the developmental course of depression and anxiety, with our own research showing distinct developmental pathways leading to depression, and differences in outcomes. For example, some children show chronic or escalating mental health difficulties; others (even those at high risk) do not develop anxiety and depression. Understanding when, how and in whom to intervene to reduce risk is important to prevent anxiety and depression and to improve outcomes. We aim to identify early predictors of risk (social, clinical and genetic), consider protective mechanisms that build mental health resilience and optimise outcomes, and test the causal role of identified risk and protective factors.

Through comparison with other cohorts, we will test the extent to which findings generalise, and what the reasons are for increases in youth depression and anxiety in more recent generations of young people.

Impact of research: 
Depression and anxiety typically have their origins in childhood and adolescence. They are also associated with substantial burdens for individuals, families and society as a whole. The study will improve our understanding of which young people are most at risk, which risk and protective factors have the potential to delay or prevent onset or improve outcomes, and the reasons behind population-level changes in youth mental health. Findings thus have the potential to inform ongoing and future development of preventive interventions for youth depression and/or anxiety, and to inform policy responses to improve youth mental health. We will work closely with relevant stakeholders (youth advisory groups, policy makers, mental health practitioners, schools and the third sector) through the course of the project to maximise the translational potential of findings from this project. Findings will also inform ongoing development/evaluation of new youth anxiety and depression intervention programmes by our group. These include an intergenerational intervention to prevent depression in young people at high familial risk; a mental health tool kit for use in schools; whole school interventions to promote mental health.
Date proposal received: 
Wednesday, 9 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Development, Genetic epidemiology

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

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

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

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

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

B3991 - Exploring the determinants and consequences of eating architecture - 17/02/2022

B number: 
B3991
Principal applicant name: 
Kaitlin Wade | Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Francisca Ibacache Fuentes, Professor Nic Timpson, Dr Kate Northstone
Title of project: 
Exploring the determinants and consequences of eating architecture
Proposal summary: 

This PhD project aims to study the underlying relationship between eating architecture (initially understood as size, timing and frequency of eating, but intended to be expanded to other aspects of nutrition such as dietary patterns, macronutrients and food preference) and adiposity-related traits in the population.

Exploring the determinants of nutrition-related behaviours, especially related to obesity – currently one of the major public health problems of the westernized world – may contribute to the understanding of the complex interactions between genetics, physiology, environment surrounding people’s eating behaviours.

Impact of research: 
Understanding the complex interactions between genetics, physiology and environment surrounding people’s eating behaviours and its relation to the development of obesity in children, might lead to stratified approaches to its prevention and treatment, which is crucial for dealing with the current obesity epidemic that is known to have a multi-factorial aetiology.
Date proposal received: 
Friday, 4 February, 2022
Date proposal approved: 
Monday, 14 February, 2022
Keywords: 
A combination of genetic epidemiology and epidemiology, behaviour and adiposity measures., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, GWAS, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., BMI, Genetic epidemiology, Genome wide association study, Mendelian randomisation, Nutrition - breast feeding, diet

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

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