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.

Click here to export results in Word format.

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

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

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

B4199 - The impact of command hallucinations and delusions of thought interference on suicidal behaviours - 21/11/2022

B number: 
B4199
Principal applicant name: 
Clara Humpston | University of York (United Kingdom)
Co-applicants: 
Title of project: 
The impact of command hallucinations and delusions of thought interference on suicidal behaviours
Proposal summary: 

Auditory verbal hallucinations are conceptualised as hearing voices or a sense of being communicated to without any external speaker present. Historically viewed as hallmarks of psychosis and other serious mental illnesses, we now know that nonclinical voices can occur with varying intensities and frequencies in the general population too. However, clinical voices such as those of a commanding nature often contribute to severe levels of distress and dysfunction, especially when the voices command the voice-hearer to carry out harmful actions against their will. Related phenomena, called delusions of (thought) interference, include thought insertion and delusion of control, defined as the feeling that someone external is sending or forcing thoughts into a person's mind and being under the influence of an external power, respectively. Command hallucinations, delusion of control and thought insertion breach if not erase the boundary between one's self and other, thus leading to a confusion between internal and external events which can make the commands exceedingly difficult to resist. Sometimes both the distress caused by and the coercive nature of such experiences can lead to suicidal feelings and behaviours including acts of self-harm. This project aims to investigate the relationships between such command hallucinations, inserted thoughts and suicidal behaviours by studying their trajectories, how they develop and change over time, as well as clarifying the impact of these experiences on individuals' mental wellbeing versus diagnoses of mental illness.

Impact of research: 
Better understanding of command hallucinations and thought insertion and their effects on suicidal behaviours in psychoses and related disorders - clinicians need to actively enquire about self-harm in psychotic disorders and any related thought interference symptoms rather than assuming the behaviours are due to a personality disorder when presented with self-harm for example.
Date proposal received: 
Monday, 14 November, 2022
Date proposal approved: 
Monday, 21 November, 2022
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Cognition - cognitive function

B4198 - Revisiting the associations between asthma and psychotic experiences - 21/11/2022

B number: 
B4198
Principal applicant name: 
Golam Khandaker | Head, Immunopsychiatry Programme, MRC IEU, Bristol Medical School (United Kingdom)
Co-applicants: 
Dr Christina Dardani
Title of project: 
Revisiting the associations between asthma and psychotic experiences
Proposal summary: 

Asthma is a chronic condition influencing breathing and characterised by breathlessness, coughing and chest tightness. Asthma can be triggered by exposure to several allergens (e.g., pollen) or infections and is considered predominantly an inflammatory condition. There is increasing evidence suggesting that asthma in childhood may be linked to a number of adverse mental health outcomes including psychotic disorders such as schizophrenia and bipolar disorder. Specifically, previous studies using the ALSPAC resource have found evidence of associations between asthma at age 10 and psychotic experiences at age 13. Furthermore, studies using large nationwide data from Sweden, found that asthma in parents was associated with bipolar disorder in their children. The reasons underlying these associations are largely unknown and several explanations have been hypothesised. For example, it has been proposed that inflammatory mechanisms involved in asthma might be causal for psychotic disorders. Gaining a better understanding on the relationship between asthma and psychotic disorders can have important implications towards uncovering drug targets for these chronic mental health conditions.

Impact of research: 
Date proposal received: 
Monday, 14 November, 2022
Date proposal approved: 
Monday, 21 November, 2022
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, Mendelian randomisation

B4200 - Plant-based diets iodine and neurodevelopmental outcomes - 21/11/2022

B number: 
B4200
Principal applicant name: 
Sarah Bath | University of Surrey
Co-applicants: 
Dr Kathryn Hart
Title of project: 
Plant-based diets, iodine, and neurodevelopmental outcomes.
Proposal summary: 

Iodine deficiency during pregnancy can result in impaired thyroid function and lead to altered brain structure. We have shown that even mild-to-moderate ID in UK pregnant women is associated with lower child IQ and reading scores at age 8-9 years.

Recent dietary recommendations promote plant-based diets for environmental sustainability and such diets are increasingly popular, particularly among young women. Since plant foods have low iodine content and animal foods are the main contributors to iodine intake, plant-based diets may increase the risk of iodine deficiency. Such diets, with high vegetable intake, may also be high in goitrogens (foods that may reduce the absorption and use of iodine in the body). A diet high in goitrogens but low in iodine may increase the risk of ID and its effects on child neurodevelopment, but there is a lack of data in this area.

In this project we plan to investigate whether a dietary risk score that considers both iodine intake and iodine inhibitors can predict mother's iodine status and thyroid function in pregnancy, and also child cognitive outcomes (e.g. IQ).

Impact of research: 
Further evidence of the role of iodine in pregnancy in areas of mild-to-moderate deficiency, building on our previous work with ALSPAC data.
Date proposal received: 
Monday, 21 November, 2022
Date proposal approved: 
Monday, 21 November, 2022
Keywords: 
Nutrition, Statistical methods, Nutrition - breast feeding, diet

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.

B4190 - Social behaviour and communication in context A multivariate genomic study of precursors and later-life outcomes - 21/11/2022

B number: 
B4190
Principal applicant name: 
Beate M St Pourcain | Max Planck Institute for Psycholinguistics (Netherlands)
Co-applicants: 
Professor Simon Fisher, Danielle Admiraal
Title of project: 
Social behaviour and communication in context: A multivariate genomic study of precursors and later-life outcomes
Proposal summary: 

Background
Mastering motor milestones and social personal skills may lead to a developmental transition that initiates a cascade of developmental changes, including social interaction and language learning(1). For example, the onset of walking(1,2) and sitting skills(3) but also social-personal skills can predict children's vocabulary size, which may potentially affect literacy-related abilities in later life. Similarly, early abilities to distinguish prosody and rhythm may affect children’s progress in learning language and (social) communication. For example, musical rhythmicity is strongly linked to cognition due to the synchronization of the partner's language expression in social communication(4).
Various studies have shown the genetic overlap between interpersonal milestone development and neurodevelopmental disorders. For example, individuals diagnosed with Autism Spectrum Disorder (ASD) show delayed development of cognitive and social functioning and, therefore, may reach early developmental milestones later (smiling, walking, spoon feeding themselves, crawling) or not at all(5).

This project will use data from ALSPAC and other large cohorts to investigate the genetic architecture of early social/communicative/language abilities as well as social /social communication abilities during the life course within large consortia (e.g. meta-Genome Wide Association Analyses (GWAS) within the EAGLE consortium) including in-depth structural models of genetic factors. The study will biologically annotate the genetic architecture of early social/communicative abilities as well as social abilities through genetic enrichment and variance partitioning analyses. Once social behaviour has been modelled genetically, we will derive genetic tools to identify genetic overlap with neuro-developmental disorders and other health-related, educational and (social) behavioural outcomes in later life, as well as brain-related encodings (e.g. brain structure and function). The project will finally assess evidence for correlation and causal mechanisms linking precursors of social/communicative abilities (e.g. musicality, motor behaviour and temperament) to social performance and, in turn, social behaviour and social communication skills to later-life outcomes (e.g. health, education, behaviour).

1. Walle, E. A. Infant Social Development across the Transition from Crawling to Walking. Front. Psychol. 7, (2016).
2. Walle, E. A. & Campos, J. J. Infant language development is related to the acquisition of walking. Dev. Psychol. 50, 336–348 (2014).
3. Libertus, K. & Violi, D. A. Sit to Talk: Relation between Motor Skills and Language Development in Infancy. Front. Psychol. 7, (2016).
4. Ravignani, A., Honing, H. & Kotz, S. A. Editorial: The Evolution of Rhythm Cognition: Timing in Music and Speech. Front. Hum. Neurosci. 11, 303 (2017).
5. Kuo, S. S. et al. Developmental Variability in Autism Across 17 000 Autistic Individuals and 4000 Siblings Without an Autism Diagnosis: Comparisons by Cohort, Intellectual Disability, Genetic Etiology, and Age at Diagnosis. JAMA Pediatr. 176, 915–923 (2022).

Impact of research: 
Date proposal received: 
Wednesday, 2 November, 2022
Date proposal approved: 
Monday, 14 November, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), GWAS, Statistical methods, Childhood - childcare, childhood adversity, Communication (including non-verbal), Genetic epidemiology, Genetics, Genomics, Genome wide association study, Speech and language

B4189 - Methods to Detect and Adjust for Selection Bias - 14/11/2022

B number: 
B4189
Principal applicant name: 
Apostolos Gkatzionis | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdom)
Co-applicants: 
Professor Kate Tilling
Title of project: 
Methods to Detect and Adjust for Selection Bias
Proposal summary: 

Biomedical research is often hindered by the presence of missing data. For example, missing data can occur due to study participants' unwillingness to disclose sensitive information about themselves (e.g. refusing to answer questions related to their mental health, smoking habits, alcohol consumption or drug use). In our research, we will develop novel statistical methodologies to assess the impact of missing data in epidemiologic studies, understand under which conditions the presence of missing data will bias an applied analysis, and overcome this form of bias.

Impact of research: 
Our research is of methodological nature and will not have a direct impact on medical practice. However, we hope that it will be helpful to applied researchers working with datasets that contain missing data, or are subject to selection bias. This may include other ALSPAC users.
Date proposal received: 
Wednesday, 2 November, 2022
Date proposal approved: 
Monday, 14 November, 2022
Keywords: 
Statistics/methodology, Diseases/conditions/variables for which data are requested: obesity (body mass index), alcohol consumption, smoking, depression, self-harm. Also pregnancy-related variables. (Listed under "other" as the list does not allow for selecting multiple diseases/conditions), Statistical methods, Birth outcomes

B4192 - Assessing the robustness of multiple imputation strategies in practice - 14/11/2022

B number: 
B4192
Principal applicant name: 
Elinor Curnow | University of Bristol (United Kingdom)
Co-applicants: 
Professor Kate Tilling, Dr Jon Heron, Dr Rosie Cornish
Title of project: 
Assessing the robustness of multiple imputation strategies in practice
Proposal summary: 

Around 14,000 children initially participated in ALSPAC. Over time, many children have been lost to follow-up (“drop-out”) or have participated at some time-points and not at others (“sporadic non-response”). Missing data due to non-response can lead to bias when estimating associations. Multiple imputation (MI) is an analysis strategy that can correct this bias, by recovering information about the missing values using observed variables (“predictors”). However, there are methodological challenges with the correct application of MI. The aim of this project is to assess their impact in practice, and develop an automated expert system to guide researchers through the multiple decisions required when using MI.

Impact of research: 
The likely output of this research will be at least one publication in a peer-reviewed epidemiology journal, the impact of which may be improved practice by researchers when performing analyses with missing data.
Date proposal received: 
Friday, 4 November, 2022
Date proposal approved: 
Monday, 14 November, 2022
Keywords: 
Statistics/methodology, Cognitive impairment, Obesity, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods

B4193 - Examining the aetiology of alcohol use in autistic adults - 14/11/2022

B number: 
B4193
Principal applicant name: 
Evie Stergiakouli | MRC IEU
Co-applicants: 
Miss Stephanie Page
Title of project: 
Examining the aetiology of alcohol use in autistic adults
Proposal summary: 

Alcohol use is a major issue for the UK healthcare system. Little is known about the link between autism and alcohol use, but preliminary research suggests that autistic adults who drink are twice as likely to become dependent as their neurotypical counterparts (1; 2). This does not seem to be the case for autistic adolescents (but existing studies are limited methodologically by small sample sizes and cross-sectional study designs) (3). Using longitudinal population-based studies to understand alcohol use in autistic adolescents going into young adulthood could address these issues. Doing this while controlling for potential confounders will help us understand what influences the development of this association over time.
Further, it is unclear whether genetics influence this association. Exposure-outcome associations are often estimated without accounting for genetic confounding in epidemiological studies, leading to potential inaccuracies (4). A genetic variant in the autism susceptibility candidate 2 gene (AUTS2) has been found to be associated with alcohol consumption (5), but it is unclear whether there are other genetic variants associated with autism that influence alcohol use. To assess this, we could calculate polygenic risk scores for autism and explore their association with alcohol use. This will help us ascertain whether genetic overlap plays a role in the aetiology of this association and potentially improve the accuracy of future causal estimates.
(1) Bowri, M., Hull, L., Allison, C., Smith, P., Baron-Cohen, S., Lai, M. C., & Mandy, W. (2021). Demographic and psychological predictors of alcohol use and misuse in autistic adults. Autism, 25(5), 1469–1480. https://doi.org/10.1177/1362361321992668

(2) Butwicka, A., Långström, N., Larsson, H., Lundström, S., Serlachius, E., Almqvist, C., Frisén, L., & Lichtenstein, P. (2017). Increased Risk for Substance Use-Related Problems in Autism Spectrum Disorders: A Population-Based Cohort Study. Journal of Autism and Developmental Disorders, 47(1), 80–89. https://doi.org/10.1007/s10803-016-2914-2

(3) Arnevik, E. A., & Helverschou, S. B. (2016). Autism spectrum disorder and co-occurring substance use disorder - A systematic review. In Substance Abuse: Research and Treatment (Vol. 10, pp. 69–75). Libertas Academica Ltd. https://doi.org/10.4137/SART.S39921

(4) Pingault, J. B., Rijsdijk, F., Schoeler, T., Choi, S. W., Selzam, S., Krapohl, E., O’Reilly, P. F., & Dudbridge, F. (2021). Genetic sensitivity analysis: Adjusting for genetic confounding in epidemiological associations. PLOS Genetics, 17(6), e1009590. https://doi.org/10.1371/JOURNAL.PGEN.1009590

(5) Schumann, G., Coin, L. J., Lourdusamy, A., Charoen, P., Berger, K. H., Stacey, D., Desrivières, S., Aliev, F. A., Khan, A. A., Amin, N., Aulchenko, Y. S., Bakalkin, G., Bakker, S. J., Balkau, B., Beulens, J. W., Bilbao, A., de Boer, R. A., Beury, D., Bots, M. L., … Elliott, P. (2011). Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7119–7124. https://doi.org/10.1073/PNAS.1017288108

Impact of research: 
To our knowledge, this will be the first ever longitudinal study to look at alcohol use in autistic adolescents going into young adulthood. This will help us understand whether associations emerge at a certain age and the direction of any association. It will also help us understand whether any association is driven by confounders. Further, the second study will help us understand whether genetics influence the association between autism and alcohol use. This could help to improve future causal estimates and thus our understanding of this relationship.
Date proposal received: 
Monday, 7 November, 2022
Date proposal approved: 
Monday, 14 November, 2022
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Developmental disorders - autism, Statistical methods, Statistical methods

B4195 - What makes clocks tick Mapping determinants of epigenetic age acceleration in early life - 15/11/2022

B number: 
B4195
Principal applicant name: 
Charlotte Cecil | Erasmus University Medical Center (the Netherlands)
Co-applicants: 
Rosa Mulder, PhD, Dr Matthew Suderman
Title of project: 
What makes clocks tick? Mapping determinants of epigenetic age acceleration in early life
Proposal summary: 

DNA methylation, the binding of a methyl-group to the DNA structure, can affect gene transcription and is related to aging. So strongly, in fact, that DNA methylation at specific sites (i.e. ‘CpGs’) can be used to estimate a persons’ age through the use of so-called ‘epigenetic clocks’. Not only do the age estimates produced by epigenetic clocks relate highly to chronological age, but the extent to which they deviate from chronological age is an important predictor of health: in adults, epigenetic age acceleration (i.e. being epigenetically older than one’s age) relates to greater disease risk and mortality, whereas conversely, deceleration relates to better health and longevity.
Research from our group suggests that an individual’s epigenetic age acceleration might be determined early on. We brought together the world’s largest developmental datasets with repeated epigenetic assessments to map how DNA methylation patterns change over the first two decades of life. We found that sites that make up epigenetic clocks already show substantial differences between individuals in early life, sometimes even from birth. This raises the possibility that longevity differences apparent in old age may already be influenced by factors occurring at a young age, opening new opportunities for early detection and intervention.
Here, we aim to identify the early origins of epigenetic aging, by examining the contribution of genetic and environmental influences, beginning in pregnancy. To do so, we use individual-level DNA methylation patterns of change at clock CpGs, already created. In addition, we will study early outcomes of inter-individual variation in early epigenetic age acceleration at the molecular and system-level.

Impact of research: 
We think we can identify early genetic and environmental determinants of epigenetic age acceleration and identify early health outcomes. This research would help us understand the mechanism of biological aging and identify potential targets of intervention, to help people age healthily.
Date proposal received: 
Wednesday, 9 November, 2022
Date proposal approved: 
Friday, 11 November, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Allergy, Epilepsy, Hypertension, Infection, Learning difficulty, Mental health, Obesity, Pain, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Respiratory - asthma, Speech/language problem, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cancer, Chronic fatigue, Cognitive impairment, Diabetes, Eating disorders - anorexia, bulimia, Eczema, GWAS, Metabolomics, Microarrays, RNA, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Genomics, Genome wide association study, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Epigenetics, Expression, Genetic epidemiology

B4187 - Inter-generational transmission of intimate partner violence and abuse IPVA influence of IPVA measures patterns and timing - 08/11/2022

B number: 
B4187
Principal applicant name: 
Alexa Yakubovich | Dalhousie University (Canada)
Co-applicants: 
Alexis Bragman, George Kephart
Title of project: 
Inter-generational transmission of intimate partner violence and abuse (IPVA): influence of IPVA measures, patterns, and timing
Proposal summary: 

Around one-quarter of young people in the UK report intimate partner violence and abuse (IPVA, that is, physical or sexual violence, or emotional abuse) among their parents by age 16. Research in US student samples suggests that for these young people, they are more likely to be victimised in their own intimate relationships as adolescents and young adults, this association my vary according to the timing of exposure to parental IPVA, and may be even higher for those with other adverse childhood experiences, such as maltreatment or parental mental illness. However, this has rarely been studied in a general population sample, or in the UK. Further, little is known about the burden
of continued IPVA over the life-course on later health, that is, witnessing IPVA among parents to then experiencing IPVA in one’s own relationship. However, IPVA among parents does not guarantee future IPVA, and many go on to not to experience this in their own intimate relationships. Understanding what factors (e.g. parent-child relationships, school, peers) help to break the cycle of intimate partner violence, can inform policies and interventions to prevent further violence and improve quality of life in these families.

Impact of research: 
Existing research on the intergenerational transmission of IPV is limited because studies tend to only ask participants about their exposure to IPV between their parents once they have already reached adulthood. This retrospective research may be biased because people experiencing IPV in adulthood may be more or less likely to classify their childhood experiences as violent compared to those who are not currently experiencing IPV. Our research will allow us to produce a more robust understanding of the measurement and occurrence of the intergenerational transmission of IPVA in the general population, and the UK population in particular. It will help determine to what extent parental IPVA drives offspring IPVA beyond other co-occurring childhood experiences and whether the timing or chronicity of exposure to parental IPVA is importance to this association. In addition, we will be able to examine the cumulative impacts of exposure to IPVA over the life course on health and wellbeing. Our findings will inform future directions for national and international research on IPVA and the potential effectiveness of intervention strategies focused on early childhood and family environments. This research will thus be of interest to public health practitioners and researchers in the fields of adverse childhood experiences, resilience, and domestic and dating violence.
Date proposal received: 
Tuesday, 1 November, 2022
Date proposal approved: 
Tuesday, 8 November, 2022
Keywords: 
Epidemiology, Intimate Partner Violence and Abuse, Statistical methods

B4194 - Genetic Determinants of Longitudinal Changes in Anthropometric Traits - 09/11/2022

B number: 
B4194
Principal applicant name: 
Loic Yengo | Institute for Molecular Bioscience - The University of Queensland (Australia)
Co-applicants: 
Dr Nicole Warrington, Mr Samuel McEwan, Dr Geng Wang , Dr Christopher Flatley , Professor Kate Tilling, Professor Deborah Lawlor
Title of project: 
Genetic Determinants of Longitudinal Changes in Anthropometric Traits
Proposal summary: 

This project aims to identify and characterize the contribution of genetic variation to growth-related traits. One part of this project will be conducted in collaboration with international consortia to identify genetic variants associated with height and body mass index (BMI) variation across childhood. The other part of the project will focus on genetic variants already associated with adult traits (height and BMI) and will characterise the critical time periods in childhood development when these variants start and stop to exert their effects.

Impact of research: 
Our research will expand knowledge of (i) the genetic determinants of healthy growth and their interplay with the environment and (ii) illuminate how maternal characteristics may impact children's future health.
Date proposal received: 
Tuesday, 8 November, 2022
Date proposal approved: 
Tuesday, 8 November, 2022
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, Hypertension, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Gene mapping, GWAS, Statistical methods, Blood pressure, BMI, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Puberty, Statistical methods, Cardiovascular, Development, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Hormones - cortisol, IGF, thyroid

B4021 - longitudinal modeling of high-dimensional molecular measurements in birth cohort studies - 07/11/2022

B number: 
B4021
Principal applicant name: 
Dennis Wang | Singapore Institute for Clinical Sciences (Singapore)
Co-applicants: 
Dr Mauricio Alvarez, Ai Ling Teh, Dr Arthur Leroy, Dr Pan Hong, Dr Varsha Gupta, Michelle Kee, Dr Evelyn Lau
Title of project: 
longitudinal modeling of high-dimensional molecular measurements in birth cohort studies
Proposal summary: 

Our group at the Singapore Institute for Clinical Sciences and the University of Manchester have received funding from the Wellcome Trust to investigate the machine learning modelling techniques for high-dimensional measurements from population studies. Recently, high-throughput 'omics technologies have allowed us to collect large numbers of molecular measurements from a single sample. Analysing these large datasets poses a problem, because existing techniques do not allow us to analyse all measurements jointly as outcomes. We will develop a statistical technique for jointly analysing large numbers of molecular measurements, using recent advances in statistical inference, as well as applying prior knowledge to reduce the number of relationships between measurements that needs to be explored. Additionally, we will develop a method for designing longitudinal studies to gain optimal information about these high-dimensional outcomes. The benefits of our approach will be two-fold: First, in allowing us to gain additional information about the relationships between longitudinal measurements, and second in improving the design of future studies, which will lead to time and cost savings.

Impact of research: 
The benefits of our approach will be two-fold: First, in allowing us to gain additional information about the relationships between longitudinal measurements, and second in improving the design of future studies, which will lead to time and cost savings for future population studies.
Date proposal received: 
Monday, 31 October, 2022
Date proposal approved: 
Monday, 7 November, 2022
Keywords: 
Bioinformatics, This is only for methodology development, but we will test models of association between molecular factors and any disease outcome observed in >100 subjects., Computer simulations/modelling/algorithms, Epigenetics, Expression, Genome wide association study, Statistical methods

B4178 - Validation of selected candidate blood metabolites biomarkers for age at menopause - 07/11/2022

B number: 
B4178
Principal applicant name: 
Despoina Manousaki | CHU Sainte-Justine (Canada)
Co-applicants: 
Mojgan Yazdan Panah, Dr, Nahid Yazdan Panah, Dr
Title of project: 
Validation of selected candidate blood metabolites biomarkers for age at menopause
Proposal summary: 

Female reproductive longevity, controlled by the timing of menarche and menopause, can vary greatly depending on genetics, lifestyle, and environmental exposures. While variations in age at menarche (AAM) and age at natural menopause (ANM) have a complex multi-factorial aetiology, the biological mechanisms underlying these variations are still not fully understood. Identifying biomarkers allows for a better understanding of the pathophysiology underpinning variations in AAM and ANM and their interconnection, while the same molecules could represent potential targets to pharmacologically modify timing of these events. High-throughput metabolomics studies have led to the discovery of a number of candidate biomarkers for a variety of traits. However, simultaneous measurement of hundreds of circulating metabolites in case-control studies is cost prohibitive and subject to confounding and reverse causation. Large genome-wide association studies (GWAS) have become available for both metabolites and AAM and ANM, advancing our knowledge on the genetic determinants of these traits. Mendelian randomisation (MR) is an established method in genetic epidemiology that explores whether a modifiable exposure is causally linked to an outcome by using genetic variants for this exposure as instrumental variables. The MR design can avoid potential bias from confounding that are typical in conventional observational studies by taking advantage of the fact that inherent genetic variants are not susceptible to environmental risk factors and reverse causation. In a setting known as two-sample MR, GWAS data for an exposure and an outcome measured in independent populations can be used to test causality of risk factors on complex health outcomes.
By employing two-sample MR, we screened hundreds of previously measured circulating metabolites for causal association with AAM and ANM. Genetic variants associated with each metabolite were extracted from four large metabolomic GWAS and effects of these variants on AAM and ANM were retrieved from the largest GWAS conducted for AAM (N = 329,345), and ANM (N = 200,000). We discovered 12 blood metabolites with evidence of a causal relationship with the AAM and 114 metabolites associated with ANM. Using multivariable MR, we found that the majority of these metabolites affect the timing of AAM or ANM regardless of body mass index (BMI). These molecules cluster in specific pathways, such as that of amino acid synthesis and glycerophosphocholine synthesis. We identified two of the candidate metabolites for AAM as significantly associated with ANM in ALSPAC participants (data requested as part of a separate project [B3667], aiming to predict AAM using a combination of genetic and non-genetic risk factors). Specifically we found an association between higher phosphatidylcholine levels and a later onset of AAM, and a link between lower isoleucine levels and an earlier onset of AAM, and the magnitude of the effects were comparable with those of the MR study. In this proposal, we request data on metabolites levels and AAM of ALSPAC mothers, in order to seek validation for a portion of the 114 candidate metabolites for ANM prioritized by our MR study, which have been measured in ALSPAC. This validation will provide further support to our MR findings, suggesting a causal role of the above metabolites in ANM.

Impact of research: 
We were able to identify circulating metabolites potentially influencing reproductive longevity using MR and follow-up pathway analyses. Notably, choline-containing phospholipids appear to influence both early puberty and menopause timing. The validation in ALSPAC of two metabolites for AAM is promising. Here, we week validation of additional candidate metabolites for ANM in ALSPAC. The results of this analysis can potentially provide an additional line of evidence to our MR findings and further support the idea that differences in the metabolic profiles of women with different pubertal or menopausal timing, while also uncovering new biological pathways underlying female reproductive aging.
Date proposal received: 
Wednesday, 2 November, 2022
Date proposal approved: 
Monday, 7 November, 2022
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc.

B4174 - Better understanding the inter-generational transmission of intimate partner violence and abuse - 07/11/2022

B number: 
B4174
Principal applicant name: 
Alexa Yakubovich | Dalhousie University (Canada)
Co-applicants: 
Dr. Annie Herbert, UoB, Dr. Jon Heron, UoB, Gene Feder, Alexis Bragman, Bridget Steele, George Kephart, Jennifer Silcox
Title of project: 
Better understanding the inter-generational transmission of intimate partner violence and abuse
Proposal summary: 

Around one-quarter of young people in the UK report intimate partner violence and abuse (IPVA, that is, physical or sexual violence, or emotional abuse) among their parents by age 16. Research in US student samples suggests that for these young people, they are more likely to be victimised in their own intimate relationships as adolescents and young adults, this association my vary according to the timing of exposure to parental IPVA, and may be even higher for those with other adverse childhood experiences, such as maltreatment or parental mental illness. However, this has rarely been studied in a general population sample, or in the UK. Further, little is known about the burden of continued IPVA over the life-course on later health, that is, witnessing IPVA among parents to then experiencing IPVA in one’s own relationship. However, IPVA among parents does not guarantee future IPVA, and many go on to not to experience this in their own intimate relationships. Understanding what factors (e.g. parent-child relationships, school, peers) help to break the cycle of intimate partner violence, can inform policies and interventions to prevent further violence and improve quality of life in these families.

Impact of research: 
Existing research on the intergenerational transmission of IPV is limited because studies tend to only ask participants about their exposure to IPV between their parents once they have already reached adulthood. This retrospective research may be biased because people experiencing IPV in adulthood may be more or less likely to classify their childhood experiences as violent compared to those who are not currently experiencing IPV. Our research will allow us to produce a more robust understanding of the measurement and occurrence of the intergenerational transmission of IPVA in the general population, and the UK population in particular. It will help determine to what extent parental IPVA drives offspring IPVA beyond other co-occurring childhood experiences and whether the timing or chronicity of exposure to parental IPVA is importance to this association. In addition, we will be able to examine the cumulative impacts of exposure to IPVA over the life course on health and wellbeing. Our findings will inform future directions for national and international research on IPVA and the potential effectiveness of intervention strategies focused on early childhood and family environments. This research will thus be of interest to public health practitioners and researchers in the fields of adverse childhood experiences, resilience, and domestic and dating violence.
Date proposal received: 
Tuesday, 1 November, 2022
Date proposal approved: 
Monday, 7 November, 2022
Keywords: 
Epidemiology, Violence and Abuse, Statistical methods, Childhood - childcare, childhood adversity, Fathers, Mothers - maternal age, menopause, obstetrics, Offspring, Parenting, Sex differences

Pages