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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B3251 - The Relationship between Metabolic Dysfunction and Psychosis - 13/02/2019

B number: 
B3251
Principal applicant name: 
Golam Khandaker | University of Cambridge (United Kingdom)
Co-applicants: 
Dr Benjamin Perry, Professor Peter Jones, Professor Nicholas J Wareham
Title of project: 
The Relationship between Metabolic Dysfunction and Psychosis
Proposal summary: 
Impact of research: 
An improved knowledge of metabolic development in people who are at risk of developing psychosis will provide great detail in how we may better act, and earlier, to reduce the significant burden of physical comorbidity in psychosis. A specifically tailored metabolic risk calculator may help healthcare professionals who look after people with first-episode psychosis to better consider and address cardiometabolic risk.
Date proposal received: 
Friday, 8 February, 2019
Date proposal approved: 
Wednesday, 13 February, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Diabetes, Mental health, Obesity, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Immunity, Physical - activity, fitness, function, Blood pressure, BMI, Cardiovascular, Childhood - childcare, childhood adversity, Development, Endocrine - endocrine disrupters, Environment - enviromental exposure, pollution, Hormones - cortisol, IGF, thyroid

B3256 - Using smartwatches to explore patterns of alcohol use - 14/02/2019

B number: 
B3256
Principal applicant name: 
Andy Skinner | University of Bristol
Co-applicants: 
Prof Debbie Lawlor, Prof Marcus Munafo, Chris Stone, Prof Kate Tilling , Dr Sally Adams
Title of project: 
Using smartwatches to explore patterns of alcohol use
Proposal summary: 

In this study we will explore the feasibility of using smartwatches to capture detailed information about individuals alcohol drinking behaviours. We will be using an approach called Ecological Momentary Assessment (EMA) to gather data about people's alcohol consumption as they go about their normal lives. Specifically, we will be using a new version of EMA called microEMA, which is designed to minimise the level of interuption and burden to people, whilst allowing us to capture detailed data about their drinking behaviours. We have developed a microEMA application to run on a normal, commercially available smartwatch, and will use this, alongside a more traditional questionnaire, to capture information about the type and quantity of alcoholic drinks consumed during each day, and if these drinks are consumed at home or outside the home, and in the company of others or alone. We will do this over a period of 3 months. Because we will ask people about their drinking behaviours throughout the day, we hope to capture more accurate and detailed information about their drinking behaviour with our smartwatch microEMA application than with traditional questionnaires, which people complete days afterwards, and which are known to suffer from problems related to remembering what was consumed, and other reporting biases. We can then use these data to explore differences in drinking behaviours between different groups. We will explore differences in drinking behaviour between high and low social economic position groups. This will allow us to understand, not just the differences in drinking behaviours between the two groups, but if there are differences in the way the two groups use and experience the new smartwatch-based microEMA approach, if this if different to the way they use and experience more traditional questionnaire approaches, and if new approaches like micro EMA might introduce other unexpected biases that could affect the data they collect.

Impact of research: 
1) To demonstrate the feasibility of using new wearable devices for the capture of high temporal density, longitudinal health data. These approaches could potentially be used to capture any self-report report data with high levels of detail, but low participant burden. Methods of this kind could be important in helping to address attrition in longitudinal cohort studies like ALSPAC. 2) To identify patterns in drinking behaviours, and differences in these by SEP, that could potentially be used to inform policy around alcohol and health, and interventions aimed at reducing alcohol consumption in specific groups.
Date proposal received: 
Wednesday, 13 February, 2019
Date proposal approved: 
Wednesday, 13 February, 2019
Keywords: 
Health behaviours, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Advanced phenotyping, wearable data capture alcohol

B3250 - PACE maternal mid-pregnancy Vitamin D and offspring cord blood methylation - 07/02/2019

B number: 
B3250
Principal applicant name: 
Matthew Suderman | IEU (United Kingdom)
Co-applicants: 
Elizabeth Diemer
Title of project: 
PACE maternal mid-pregnancy Vitamin D and offspring cord blood methylation
Proposal summary: 

Low maternal vitamin D during pregnancy has been associated with a wide range of health outcomes in offspring, including bone health, symptoms of Attention Deficit-Hyperactivity Disorder, symptoms of Autism Spectrum Disorder, and autoimmune conditions. Methylation is one mechanism by which maternal vitamin D in the prenatal period might impact offspring health. We propose to test associations between maternal mid-pregnancy Vitamin D and offspring cord blood methylation. To maximise power, we will meta-analyze associations in multiple cohort studies including ALSPAC within the Pregnancy and Childhood Epigenetics consortium (https://www.niehs.nih.gov/research/atniehs/labs/epi/pi/genetics/pace/ind...).

Impact of research: 
A final answer about whether or not maternal serum vitamin D levels during pregnancy affects cord blood methylation. If the answer is positive, then we will be closer to understanding how maternal vitamin D levels affect offspring.
Date proposal received: 
Tuesday, 5 February, 2019
Date proposal approved: 
Thursday, 7 February, 2019
Keywords: 
Epigenetic epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Microarrays, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Nutrition - breast feeding, diet

B3248 - Alcohol use breastfeeding and offspring neurodevelopment - 05/02/2019

B number: 
B3248
Principal applicant name: 
Luisa Zuccolo | University of Bristol, MRC Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Matt Tudball, Jon Heron, Cheryl McQuire
Title of project: 
Alcohol use, breastfeeding and offspring neurodevelopment
Proposal summary: 

Breastfeeding is recommended as the best source of nutrition in early life by the WHO. However, mothers who consume large quantities of alcohol while breastfeeding might be harming their offspring because of this ‘passive’ alcohol exposure in the postnatal period. Realistically, in the UK and other developed countries, only a minority of mothers will be consuming alcohol to excess while breastfeeding and caring for a young baby, while most mothers would consume alcohol occasionally and in moderate quantities. These levels of consumption have not been linked with definite harms or benefits to the child so far, with only a few studies examining this question and achieving conflicting results. We propose to investigate the association between early post-natal alcohol exposure and measures of offspring physical and neurological development, including risk of Foetal Alcohol Spectrum Disorder (FASD), in a large UK-based sample representative of the population and followed-up since antenatal appointments, the Avon Longitudinal Study of Parents And Children (ALSPAC).

Impact of research: 
A deeper understanding of the impact of drinking while breastfeeding could be used to inform recommendations for mothers on safe drinking behaviour in the early post-natal period.
Date proposal received: 
Thursday, 31 January, 2019
Date proposal approved: 
Tuesday, 5 February, 2019
Keywords: 
Epidemiology, Cognitive impairment, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, Breast feeding, Cognition - cognitive function, Development, Nutrition - breast feeding, diet

B3245 - Econometrics of loneliness - 30/01/2019

B number: 
B3245
Principal applicant name: 
Claryn Kung | Centre for Health Economics, Monash University (Australia)
Co-applicants: 
Professor Michael Shields, Professor David Johnston
Title of project: 
Econometrics of loneliness
Proposal summary: 

Loneliness has, in recent years, become a priority in national public health agendas in developed countries, given increasing recognition of the detrimental effects of loneliness on health and mortality. The literature has often focussed on loneliness among older adults, but recent surveys have revealed a similar prevalence among younger adults up to age 25.

The aim of this research project is to understand whether circumstances and experiences from childhood can be linked to loneliness and social isolation reported in adulthood. The ALSPAC also contains multiple reports of loneliness across teenage years and young adulthood, which would allow us to understand its dynamics; for example, whether there are different patterns of loneliness across time between individuals. Rich reports of physical and mental health, including disease-related biomarkers, would also aid in analysing relationships between loneliness and health, to complement evidence seen in later adulthood.

It is imperative to identify individuals at higher risk of loneliness in later life, and early life events or circumstances that can play an important role in predicting later life loneliness, towards reducing societal loneliness via public policy and private decisions. Identifying factors from early life, rather than contemporaneous factors, is beneficial to inform early preventive strategies, and to target such factors rather than mechanisms (via which these factors operate) for more efficient allocation of resources. Understanding whether and how loneliness is predictive of poor health earlier in life may also provide some insights into the mechanisms via which loneliness predicts excess mortality in late adulthood.

Impact of research: 
Loneliness and social isolation have been shown to be associated with premature mortality and poorer physical and mental health. It is therefore important to understand their risk factors, and in light of recent findings showing 'nature' (genetic heritability) to play a very small role in social interaction, the role of 'nurture' (environment including circumstances and experiences) may be particularly important to explore. Looking back into one's childhood circumstances in a systematic and comprehensive manner may aid in improve the design of policies and interventions designing earlier and/or more targeted interventions, towards alleviating this societal problem more efficiently. This research will also contribute to the sparse research literature on this topic, complementing the larger literature on risk factors of loneliness in later adulthood.
Date proposal received: 
Friday, 25 January, 2019
Date proposal approved: 
Wednesday, 30 January, 2019
Keywords: 
Health Economics, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Childhood - childcare, childhood adversity, Communication (including non-verbal), Social science, Statistical methods

B3246 - MAPS mapping the analytic paths of a crowdsourced data analysis - 04/02/2019

B number: 
B3246
Principal applicant name: 
Marcus Munafò | University of Bristol (UK)
Co-applicants: 
Mr Robert Arbon, Ms Katie Drax, Miss Natalie Thurlby, Prof Nic Timpson, Dr Kate Northstone, Mr Alex Kwong, Prof Kate Robson-Brown
Title of project: 
MAPS: mapping the analytic paths of a crowdsourced data analysis
Proposal summary: 

In order for the public to have faith in the conclusions of scientists it is important that the methods they employ are robust and transparent. This is especially important for controversial topics with major implications for mental health. The public should rightly demand that such findings are not contingent on the beliefs of the scientists, their particular methods, computational quirks or simple accident. This is of particular relevance when total transparency is not possible because the data is sensitive.

This study addresses the question of robustness by taking a controversial question, “Is there an association between screen time and depression and anxiety?”, recruiting teams of independent data analysts and looking at how they answer the question using the same data, effectively ‘crowd-sourcing’ the data analysis.

The study will use the answers teams provide to this controversial question to answer further questions such as: “Do the methods used to answer the question influence the result and if so by how much?” and, “Do the beliefs and particular expertise of the analysts influence their results?”. To do this, we will use a statistical technique called a ‘multiverse analysis’, whereby reasonable alternatives to choices made by the teams, during the data analysis, are explored and recorded to see how sensitive the results were to the choices made.

To ensure the study is transparent we will investigate the use of anonymised data. Using anonymised data is controversial as the anonymisation process may erase important features of the data. This study will ask “Does the anonymisation process affect the results and if so by how much?”.

The answer to all these questions will help us understand how scientists arrive at answers to controversial questions and whether crowd sourced analysis and data anonymisation techniques can ensure findings are robust and transparent.

Finally, our study will challenge the teams to come up with interesting ways to visualise the answers to these questions in exchange for a prize. Visualising the teams’ answers, along with how robust they are, in a clear, accessible way will be important to help communicate complex results both for this study and in the future.

Impact of research: 
Depending on results: Increased awareness of the effects of screen time. If appropriate, we will produce lay summaries of our findings for distribution in schools, colleges, the university and local GP practices. Increased awareness of the sensitivity of results from statistical analyses to different analytic choices Increased understanding of the logistics of carrying out a crowdsourced analysis of sensitive data
Date proposal received: 
Friday, 25 January, 2019
Date proposal approved: 
Wednesday, 30 January, 2019
Keywords: 
Statistics/methodology, Infection, Statistical methods, Childhood - childcare, childhood adversity, Statistical methods

B3244 - Are Different Face Shapes Related to Different Levels of Blood Pressure - 06/02/2019

B number: 
B3244
Principal applicant name: 
Stephen Richmond | Cardiff University
Co-applicants: 
Camilla Miles-Hobbs, Dr Alexei Zhurov, Dr Reneta Medeiros-Mirra
Title of project: 
Are Different Face Shapes Related to Different Levels of Blood Pressure?
Proposal summary: 
Impact of research: 
A reduction in blood pressure is a large public health benefit as high blood pressure is linked to many cardiovascular diseases. If a facial feature is identified to be linked to high blood pressure an appliance such as the MAD could be used to reduce this. It may provide a link between GMP and GDP, allowing shared care for patients.
Date proposal received: 
Thursday, 24 January, 2019
Date proposal approved: 
Wednesday, 30 January, 2019
Keywords: 
Dentistry, Sleep breathing disorders Facial shapes, Statistical methods, Face - face shape

B3242 - Identifying maternal and early infant biomarkers for Fetal Alcohol Spectrum Disorder - 24/01/2019

B number: 
B3242
Principal applicant name: 
Paul Yousefi | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdom)
Co-applicants: 
Luisa Zuccolo, Henry Carlton
Title of project: 
Identifying maternal and early infant biomarkers for Fetal Alcohol Spectrum Disorder
Proposal summary: 

Fetal alcohol spectrum disorders (FASDs) are lifelong disabilities caused by prenatal alcohol exposure. FASD is thought to be the leading preventable cause of developmental disability in the world and is associated with mental health problems, antisocial behaviour and substance misuse. Understanding which individuals are most at risk to develop FASD is key as it has been shown that an early diagnosis or risk identification could help with primary and secondary prevention, as well as amelioration and treatment efforts. Early identification of individuals most at risk for FASD via the identification of robust maternal and infant biomarkers will offer an early window for intervention, will focus specialist diagnostic efforts in a resource-limited healthcare system, and will contribute towards mitigating FASD-related disabilities in later life. It may also prevent or reduce foetal exposure to alcohol in subsequent pregnancies.

This project will focus on early identification of FASD by DNA methylation levels, which are known to be altered by alcohol use. Indeed, a DNA methylation alcohol (DNAm-Alc) score, comprising 144 CpG sites, was recently developed by Liu et al. that can robustly distinguish between current heavy drinkers and non-drinkers in a general population. In addition, strong evidence from animal models indicates that alcohol use during pregnancy is capable of altering offspring DNAm.

McQuire et al. have developed an algorithm to identify individuals at high risk of FASD regardless of them having received a formal (and rare!) diagnosis. We propose to compare this algorithmic identification with DNAm-based markers to find out whether prenatal risk assessment would be possible.

References
Liu, C. et al. A DNA methylation biomarker of alcohol consumption. Mol. Psychiatry 23(2):422-433 (2018)

McQuire C, Mukherjee R, Hurt L, Higgins A, Greene G, Farewell D et al. Screening prevalence of fetal alcohol spectrum disorders in a region of the United Kingdom: A population-based birth-cohort study. Prev Med (Baltim) 2019; 118: 344–351.

Impact of research: 
The primary academic beneficiaries of this project will be addiction/alcohol abuse epidemiologists and biological scientists who will gain improved alcohol intake assessment for future studies and insight into how external factor can alter the epigenome.
Date proposal received: 
Tuesday, 22 January, 2019
Date proposal approved: 
Thursday, 24 January, 2019
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc.

B3243 - Using a life course approach to disentangle the association between alcohol use and working memory as risk factors for dementia - 24/01/2019

B number: 
B3243
Principal applicant name: 
Liam Mahedy | University of Bristol (United Kingdom)
Co-applicants: 
Professor Marcus Munafo, Professor Matthew Hickman, Professor Yoav Ben-Shlomo, Dr Luisa Zuccolo, Dr Liz Coulthard
Title of project: 
Using a life course approach to disentangle the association between alcohol use and working memory as risk factors for dementia
Proposal summary: 

Dementia is one of the leading causes of death globally and increasing longevity ensures its prevalence will rise even further. As there is no known treatment that slows down the progression of this disorder, there is an emphasis to focus on cognitively healthy individuals at risk of developing dementia as the best strategy to reduce dementia incidence and prevalence. Identifying risk factors and biomarkers for dementia is increasingly important. Alcohol use and working memory have been shown to be associated with dementia, however the nature of these associations are unclear. This research project aims to use a number of methodologies novel to the field of dementia by using combination of observational and genetic techniques. This approach is essential for testing whether there are critical or sensitive periods for dementia risk and may help to uncover whether alcohol use and/or working memory performance contribute to dementia. Identifying early modifiable risk factors for dementia has the potential to gain a greater understanding of dementia progression and inform preventative interventions.

Impact of research: 
This project will have public health implications as it will provide the most robust evidence to date on the nature of the association between binge drinking and working memory in youths.
Date proposal received: 
Wednesday, 23 January, 2019
Date proposal approved: 
Thursday, 24 January, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Mental health, Statistical methods, Ageing, Cognition - cognitive function, Development, Genetic epidemiology, Genome wide association study, Intelligence - memory, Mendelian randomisation, Statistical methods, Binge drinking

B3239 - Investigating a causal link between early life infection and schizophrenia - 22/01/2019

B number: 
B3239
Principal applicant name: 
Ruth Mitchell | University of Bristol
Co-applicants: 
Dr Hannah Jones, Dr Carolina Borges, Dr Fernando Hartwig, Georgina Hamilton
Title of project: 
Investigating a causal link between early life infection and schizophrenia
Proposal summary: 

Infections during pregnancy1 and early childhood2 have been linked to increased risk of schizophrenia in observational studies. Inflammation, as measured by interleukin-6 (IL-6) and C-reactive protein (CRP), contribute to host defence against infections3,4. Observational epidemiologic studies suggest that inflammatory biomarkers have a positive association with schizophrenia. Interestingly, we have recently shown that individuals who are genetically predisposed to lower activity of the inflammatory response (i.e. CRP levels and blockade of IL-6 cell signalling) have higher risk of schizophrenia5. This, seemingly contradictive, finding may be explained by a genetically determined decreased inflammatory response resulting in an increased susceptibility to early life infection4. In this project, the link between inflammation, psychosis and early life infection will be explored using publicly available genome-wide association study (GWAS) data and newly measured antibody titres available in the ALSPAC cohort6.

1. Khandaker GM, Zimbron J, Lewis G, Jones PB. Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychol Med. 2013;43(02):239-257.
2. Khandaker GM, Zimbron J, Dalman C, Lewis G, Jones PB. Childhood infection and adult schizophrenia: A meta-analysis of population-based studies. Schizophr Res. 2012;139(1-3):161-168.
3. Calabrese LH, Rose-John S. IL-6 biology: implications for clinical targeting in rheumatic disease. Nat Rev Rheumatol. 2014;10(12):720-727.
4. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-1812.
5. Hartwig FP, Borges MC, Lessa Horta B, Bowden J, Smith GD. Association between genetically elevated levels of inflammatory biomarkers and risk of schizophrenia: a two-sample Mendelian randomisation study. 2017.
6. Mitchell RE, Jones HJ, Yolken RH, et al. Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort. Wellcome Open Res. 2018;3:49.

Impact of research: 
A deeper understanding into the causes of schizophrenia, inflammation and infection contributing to the wider scientific community
Date proposal received: 
Thursday, 17 January, 2019
Date proposal approved: 
Tuesday, 22 January, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Inflammation, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B3240 - Effect of prenatal and early childhood fluoride exposure on cognitive outcomes of children A pilot study - 22/01/2019

B number: 
B3240
Principal applicant name: 
Vida Zohoori | Teesside University (United Kingdom)
Co-applicants: 
Dr Ruth Valentine, Dr Jill McKay, Dr Roy Sanderson, Claire O'Malley, Dr Richard McNally
Title of project: 
Effect of prenatal and early childhood fluoride exposure on cognitive outcomes of children: A pilot study
Proposal summary: 

Some evidence suggests that early exposure to high levels of fluoride may have a negative impact on the cognitive outcomes in children. Given the conflicting findings from previous studies, further research is necessary to understand the effect of fluoride on cognitive development. Our aim is to assess the association of exposure to fluoride during early pregnancy and childhood with offspring cognitive development. We will study mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC) to address the aim of our study. We will estimate fluoride exposure from diet and dental products using the food frequency and oral hygiene questionnaires collected from mothers during pregnancy and from their children when 6, 15 and 24 months old. We will then investigate the link between fluoride exposure and the cognitive outcomes of offspring which were measured at 18 months of age during ALSPAC clinical assessments.

Impact of research: 
This is a pilot study which will generate valuable data for a purposely-designed larger study on the link between fluoride exposure and cognitive development and IQ. However, due to lack of current data on this issue in the UK, the results of this study could have high public health relevance for the UK, providing critical information about the safety of fluoride exposure, especially for sensitive populations such as the pregnant woman, the fetus, and very young child.
Date proposal received: 
Thursday, 17 January, 2019
Date proposal approved: 
Tuesday, 22 January, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Cognitive impairment, Computer simulations/modelling/algorithms, Cognition - cognitive function

B3241 - Investigating the causal relationship between allergic disease and psychiatric disorders - 22/01/2019

B number: 
B3241
Principal applicant name: 
Ashley Budu-Aggrey | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdom)
Co-applicants: 
Dr Hannah Sallis, Sally Joyce
Title of project: 
Investigating the causal relationship between allergic disease and psychiatric disorders
Proposal summary: 

Allergic diseases including asthma, hay fever and eczema often occur in the same individuals. Allergic diseases have been reported to be linked with depression and anxiety disorders, which is also a growing health concern. However, it is not yet clear if the allergic diseases cause depression or mental health disorders, or if these have a causal effect on allergic disease. In this project we hope to use a statistical technique called Mendelian Randomization to investigate the relationship between these traits.

Impact of research: 
Date proposal received: 
Friday, 18 January, 2019
Date proposal approved: 
Tuesday, 22 January, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Allergy, Eczema, Mental health, Respiratory - asthma, Statistical methods, Dermatology, Genetic epidemiology, Mendelian randomisation, Statistical methods

B3237 - Childhood adversity HPA-axis function and the vulnerability or resilience to stress-related psychopathology - 15/01/2019

B number: 
B3237
Principal applicant name: 
Tarani Chandola | University of Manchester/ University College London (Greater Manchester)
Co-applicants: 
Ms Stephanie Cahill, Ms Eleonora Iob
Title of project: 
Childhood adversity, HPA-axis function, and the vulnerability or resilience to stress-related psychopathology
Proposal summary: 

One of the best replicated findings in developmental research, psychology and epidemiology is that exposure to adverse childhood experiences (ACEs) predicts poorer outcomes across health and social domains. To date, the pathways underlying these relationships remain unclear. It has been proposed that exposure to ACEs may affect the development of the hypothalamic–pituitary–adrenal (HPA)-axis and lead to related vulnerability to stress-related mental health problems over the life course. Interestingly, despite the high prevalence of ACEs, some individuals do not develop stress-related dysfunctions. By better understanding the underlying mechanisms by which children exposed to adversities show later resilience, there may be opportunities to learn more about ways of intervening and preventing adverse outcomes. Overall this project aims to provide a comprehensive examination of the biopsychosocial pathways through which exposure to ACEs may affect the development of the HPA-axis, and resilience or vulnerability to stress-related psychopathology (depression/anxiety) over the life course, considering complex interplay between genetic, epigenetic and environmental factors.

Impact of research: 
Academic Impact: This research will provide a more comprehensive understanding of the aetiology of stress-related mental disorders. Additionally, it will bring about important methodological innovations owing to the use of advanced statistical methods to measure adversity clusters and the integration of sophisticated assessments of biological and genetic factors. Clinical impact: The results of this project will also have the potential to inform clinical interventions for the prevention, detection and treatment of ACEs and mental illness. These may include: psychosocial interventions to manage the negative effects of childhood adversity and reduce stress levels; pharmacological therapies to ameliorate psychiatric symptoms; and genetic testing to identify individuals at higher risk early in development and tailor treatment plans. Policy impact: Such understanding of the life course pathways linking early-life stress with mental health will advance the existing evidence base, providing policymakers with reliable and extensive data with which a more streamlined process of policy development might be better manoeuvred. This may see an increase in funding for mental health and social care trusts, improved intervention programmes in schools, and lead to an improvement in the services available for children and families
Date proposal received: 
Thursday, 10 January, 2019
Date proposal approved: 
Tuesday, 15 January, 2019
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Gene mapping, GWAS, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Hormones - cortisol, IGF, thyroid, Immunity, Mothers - maternal age, menopause, obstetrics, Offspring, Parenting, Social science, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Epigenetics, Genetic epidemiology, Genetics, Genome wide association study

B3235 - Association of adolescent physical activity profiles with hip strength at age 25 - 15/01/2019

B number: 
B3235
Principal applicant name: 
Ahmed Elhakeem | MRC Integrative Epidemiology Unit at University of Bristol (United Kingdom)
Co-applicants: 
Debbie Lawlor, Jon Tobias, Jon Heron
Title of project: 
Association of adolescent physical activity profiles with hip strength at age 25
Proposal summary: 

This study will use a latent variable (and negative control) approach to investigate association between adolescent physical activity (PA) profiles and hip bone mineral density (BMD) at age 25. The main analysis will examine relationship between PA patterns over adolescence and age 25 hip BMD by applying (2nd order) latent growth models to repeated measures of PA intensity (light, moderate, vigorous) derived from Actigraph accelerometers at ages 11, 13 and 15. An additional analysis will be performed to explore association between gravitational impacts from PA, assessed at age 17 from Newtest acceleromters, and hip BMD at age 25.

Impact of research: 
Date proposal received: 
Thursday, 10 January, 2019
Date proposal approved: 
Tuesday, 15 January, 2019
Keywords: 
Epidemiology, Statistical methods, Physical - activity, fitness, function

B3238 - Early-life nutritional programming of metabolic health through epigenetic pathways - 15/01/2019

B number: 
B3238
Principal applicant name: 
Gemma Sharp | University of Bristol (United Kingdom)
Co-applicants: 
Dr Laura Johnson
Title of project: 
Early-life nutritional programming of metabolic health through epigenetic pathways
Proposal summary: 

Pregnancy and infancy are critical periods for nutritional programming of metabolic health. Epigenetic changes seem to have a crucial role in pathways leading from early-life nutrition to metabolic health across the life course. The NUTRIprogram consortium (University of Bristol, Erasmus University Rotterdam, IS-Global Barcelona, University of British Columbia and LMU) has been set up to facilitate research in this area. We will study key maternal and infant nutrition-related exposures in relation to DNA methylation in mothers and offspring at different ages, and metabolic health across the life course.

Impact of research: 
NutriPROGRAM will develop a sustainable, translational, international collaboration for studies on nutrition and epigenetics and their role in sustaining good health throughout the life course.
Date proposal received: 
Thursday, 10 January, 2019
Date proposal approved: 
Tuesday, 15 January, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Nutrition/diet, Metabolomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Mothers - maternal age, menopause, obstetrics, Offspring, Physical - activity, fitness, function, Birth outcomes, Blood pressure, Childhood - childcare, childhood adversity, Development, Epigenetics, Fathers, Genetic epidemiology, Mendelian randomisation

B3236 - A Recall by Genotype Study to investigate the role of common TRPA1 variants in acute pain perception - 22/01/2019

B number: 
B3236
Principal applicant name: 
Jim Dunham | University of Bristol
Co-applicants: 
Prof. Tony Pickering, Prof. Nic Timpson
Title of project: 
A Recall by Genotype Study to investigate the role of common TRPA1 variants in acute pain perception.
Proposal summary: 

Why do some people suffer with long term pain after an accident or surgery whilst another person recovers without incident? We believe that part of the answer lies in the subtle differences in people's genes. We are interested in how these little differences can add up to make an individual more or less likely to suffer from pain. Unfortunately we don't know at the moment which gene differences are important. We plan to invite people, from the ALSPAC cohort, with known common variants in a specific gene that has been linked to pain detection (TRPA1), to come for testing of their sensitivity to mildly painful stimulation. If we find people who have differences in their pain sensitivity, we will invite them back for more detailed tests. In these detailed tests, we will record the activity in their nerves during mildly painful stimulation to see if a change in their nerve activity underlies their differences in pain sensitivity.

The mildly painful stimulation that we use is well tolerated by both patients and volunteers. Most of our tests look at pain "threshold" e.g. the transition from warm to hot. We therefore use the lowest temperature that causes pain to be perceived. We will also ask participants to rate how much pain they feel in response to a given stimulus. We believe that these tests are less painful then giving blood or a skin biopsy. The participant can stop the experiment at any time if it is too uncomfortable.

Impact of research: 
Academic impact: 1. Establish a pipeline / protocol to determine the influence of genes on acute and chronic pain. 2. Manuscripts a. Pain QST within a Recall by Genotype Paradigm. b. Human C fibre microneurography within a Recall by Genotype Paradigm. c. Demonstration of the utility of a human measure of nociceptor transduction. 3. Conference Presentations 4. Forging and Enhancing University of Bristol collaborations with other research institutions with international influence (including Oxford (U.K.), Northwestern and Washington (U.S.)). 5. Forging and Enhancing University of Bristol collaboration with industry (Lilly). 6. Forging and Enhancing interdisciplinary work within Bristol (Neurosciences with Genetic Epidemiology) and outside of Bristol (pharmaceutical industry - Lilly and US research institutions: Northwestern, Washington). Economic and societal impacts The ability to accurately risk assess members of the public and patients for their risk of enhanced acute and chronic pain will enable targeted provision of analgesia i.e. precision medicine. This has the potential to reduce unnecessary analgesic consumption (a critical need in the context of the epidemic of prescription opiate deaths) whilst also preventing pain in those most at risk. This improves quality of life for patients and promises improved economic contribution via reduction in time off work.
Date proposal received: 
Wednesday, 9 January, 2019
Date proposal approved: 
Thursday, 10 January, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)

B3234 - Nurture of Nature How Genes and Environments Interact in the Formation of Skills - 09/01/2019

B number: 
B3234
Principal applicant name: 
Victor Andres Ronda Checchia | TrygFonden’s Centre for Child Research, Aarhus University. (Denmark)
Co-applicants: 
Dorthe Bleses, Michael Rosholm
Title of project: 
Nurture of Nature: How Genes and Environments Interact in the Formation of Skills
Proposal summary: 

The goal of our research proposal is to study the interplay between genetic influences and home and school environments in the context of child development. We aim to understand how maternal and child genes jointly determine parental investments, the role of parent-child interactions and daycare access in mediating genetic influences for skill formation, and epigenetic channels through which the childhood environment can influence children’s cognitive and behavioral development.

Impact of research: 
This project aims to provide a better understanding of the following questions: What is the role of parental genes in the transmission of health and skills? How does the environment mediate the effect of genetic influences and how do genetic influences mediate the effects of intervention? What is the role of epigenetic changes in explaining gene-environment interactions?
Date proposal received: 
Thursday, 3 January, 2019
Date proposal approved: 
Wednesday, 9 January, 2019
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Speech/language problem, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Speech and language, Development, Epigenetics, Genetics, Genomics, Intelligence - memory, Parenting, Psychology - personality, Social science

B3216 - Placental Weight or Volume as a Predictor of Poor Perinatal Outcomes - 03/01/2019

B number: 
B3216
Principal applicant name: 
Debbie Lawlor | MRC-IEU, NIHR-BRC (Bristol)
Co-applicants: 
Dr. David Odd, Miss Rebecca Ellis, Ahmed Elhakeem
Title of project: 
Placental Weight or Volume as a Predictor of Poor Perinatal Outcomes
Proposal summary: 

A healthy placenta is important for a healthy pregnancy and birth of a healthy baby. Some research shows that a larger placenta is associated with a healthier baby at birth. The placenta is normally weighed after the birth of the baby. This is too late to change things during the pregnancy that might help improve the mothers and baby’s health. The size of the placenta can be measured using ultrasound scans during pregnancy. If we can show that the size of the placenta is an accurate way of identifying women who might be at risk of having health problems during pregnancy and with their baby at birth, and that ultrasound measures of the placenta are accurate measures of its size, it might be possible to prevent problems for mother and her baby.

Impact of research: 
Determining whether an association exists between placental weight/volume and adverse perinatal outcomes could help us identify ways to predict adverse outcomes, and the potential accuracy of such predictions. This in turn can be used to identify at risk pregnancies, or groups most at risk, where additional support, surveillance, or intervention may be beneficial.
Date proposal received: 
Thursday, 3 January, 2019
Date proposal approved: 
Thursday, 3 January, 2019
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Birth outcomes, BMI, Cohort studies - attrition, bias, participant engagement, ethics, Mothers - maternal age, menopause, obstetrics, Offspring, Statistical methods

B3231 - Understanding the effects of prenatal infections and other environmental and genetic risk factors on child development - 09/01/2019

B number: 
B3231
Principal applicant name: 
Bonnie Auyeung | University of Edinburgh (UK)
Co-applicants: 
Aja Murray, Tom Booth, Nicolas Chevalier, Michelle Luciano, Anna Hall, Lydia Speyer, Catherine Doust, Michael V. Lombardo
Title of project: 
Understanding the effects of prenatal infections and other environmental and genetic risk factors on child development
Proposal summary: 
Impact of research: 
Prenatal maternal infections are a potentially preventable risk factor, providing the opportunity to influence policy decisions around the prevention of maternal infection, provision of treatment and follow-up support after birth. Examining how maternal mental health may affect the relationship between infections and development will provide important information and guidance for health care practitioners in the fields of pre- and perinatal care. This work will also directly focus on the outcomes for children affected by prenatal maternal infections and mental health issues from areas with varying levels of deprivation, and help to guide policy and healthcare interventions to address inequalities. Findings will help to ensure the best possible start in life. Findings are expected to be of international interest. This work would be pivotal in helping to bridge a significant gap in our current understanding, which is limited to our knowledge from studies where hospital records are linked to diagnosis registers, where it is not possible to connect individual infection responses to specific behavioural outcomes in children.
Date proposal received: 
Friday, 14 December, 2018
Date proposal approved: 
Thursday, 20 December, 2018
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Infection, Learning difficulty, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Speech/language problem, GWAS, Microarrays, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Epigenetics, Genetic epidemiology, Genome wide association study, Mothers - maternal age, menopause, obstetrics, Statistical methods

B3230 - Characterisation of childhood and adolescent favourable adiposity alleles identifed in adults - 18/12/2018

B number: 
B3230
Principal applicant name: 
Tim Frayling | University of Exeter (UK)
Co-applicants: 
Prof Nic Timpson, Dr Kaitlin Wade, Dr Joshua Bell, Dr Emma Vincent, Matthew Lee, Prof George Davey Smith, Dr Hanieh Yaghootkar, Dr Jess Tyrrell
Title of project: 
Characterisation of childhood and adolescent "favourable adiposity" alleles identifed in adults
Proposal summary: 

We would like to access the Children of the 90s and their parents’ genetic data and some imaging and blood biomarker information in order to characterise “favourable adiposity” genes. By this we mean versions of genes (alleles) that result in a higher BMI and body fat but lower risk of diseases such as type 2 diabetes, hypertension and heart disease. Current studies have already identified 14 alleles associated with higher body fat % but lower risk of these diseases. We know that some of these “favourable adiposity” genes operate by putting more fat in the lower body, resulting in a lower waist to hip ratio (“pear” rather than “apple” shape) in women. Using MRI imaging from adults, we know that these alleles add more fat under the skin (subcutaneous) but less fat to the liver. These genes have been discovered in adults, and we would now like to test what they are doing in childhood and adolescents in the CO90s. To do this, we’d like to link the gene variants we are finding in adults to body fat imaging and circulating blood markers at all time points in childhood and adolescence where available. We’d like to analyse the parent’s data to help in the discovery of these genetic variants by analysing with other large studies of adults.

Impact of research: 
We've had a lot of interest from our three papers (all in Diabetes) on discovering these unusual variants. Most recently we had considerable interest from the media when we used these variants as an "instrument" to "uncouple" higher adiposity from it's adverse effects to show (subject to wide confidence intervals) that higher adiposity without it's adverse effects had a similar effect on depression as standard higher BMI. Our work will add to other important work in CO90s in understanding the causes and consequences of obesity in children and young adults. In the next few years it will be very interesting to see how these variants affect the offspring of C090s.
Date proposal received: 
Friday, 14 December, 2018
Date proposal approved: 
Tuesday, 18 December, 2018
Keywords: 
Genetics, Obesity, GWAS, Medical imaging, Metabolomics, NMR, BMI, Genetic epidemiology, Genetics, Genome wide association study, Liver function, Mendelian randomisation, Metabolic - metabolism

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