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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B3097 - A meta-analysis of maternal smoking GFI1-CpGs and cardio-metabolic phenotypes in adults - 17/04/2018

B number: 
B3097
Principal applicant name: 
Matthew Suderman | Integrative Epidemiology Unit
Co-applicants: 
Title of project: 
A meta-analysis of maternal smoking GFI1-CpGs and cardio-metabolic phenotypes in adults
Proposal summary: 

Individuals exposed prenatally to cigarette smoke tend to have lower birthweight and have higher risks for a variety of detrimental health outcomes later in life. Cigarette smoke exposure is also associated with DNA methylation changes at gene GFI1, and recent evidence suggests that these changes may play a role in the lower birthweight of exposed infants. We would like to determine if there is evidence that these DNA methylation changes may also play a role in risk factors for other health outcomes of prenatal cigarette smoke exposure. We would specifically like to investigate factors related to cardiovascular and metabolic health.

Impact of research: 
Evidence for or against the possibility that DNA methylation mediates the effects of prenatal smoke exposure on later health outcomes.
Date proposal received: 
Thursday, 12 April, 2018
Keywords: 
Epigenetics, cardio-metabolic risk factors, Microarrays, Biological samples -e.g. blood, cell lines, saliva, etc., Birth outcomes, Blood pressure, BMI, Cardiovascular, Environment - enviromental exposure, pollution, Epigenetics, Metabolic - metabolism

B3099 - Lung function growth and residential greenness in the ALSPAC cohort - 19/04/2018

B number: 
B3099
Principal applicant name: 
Elaine Fuertes | Imperial College London (United Kingdom)
Co-applicants: 
Dr. Debbie Jarvis, Dr. John Henderson, Dr. Osama Mahmoud
Title of project: 
Lung function growth and residential greenness in the ALSPAC cohort
Proposal summary: 

There is increasing evidence that residential greenspaces (proximity to and amount of green spaces and vegetation around a person's home) may be associated with various health outcomes, including increased physical activity levels and respiratory health outcomes, such as asthma. As lung function is associated with both physical activity and asthma, it could thus also be associated with greenspaces. However, to date, no study has examined whether an association between residential greenspaces and lung function exists in children, and what potential pathways may be playing an important role. Using the ALSPAC data, this study aims to fill this research gap.

Impact of research: 
Assuming that our hypothesis is true, this study will be the first to report positive associations between higher residential greenspace and lung function growth in children. This work thus has the potential to contribute to the growing body of evidence suggesting that surrounding greenspaces positively affect health. Of particular interest will be whether we can identify potential mechanisms that may be driving any observed link between greenspaces and lung function growth (either via physical activity, asthma, or air pollution).
Date proposal received: 
Monday, 16 April, 2018
Keywords: 
Epidemiology, Respiratory - asthma, Statistical methods, Development, Environment - enviromental exposure, pollution, Physical - activity, fitness, function, Sex differences

B3104 - Impact of Breastfeeding on Cardiovascular and Metabolic Outcomes in Women with a History of Hypertensive Disorders of Pregnancy - 26/04/2018

B number: 
B3104
Principal applicant name: 
Abigail Fraser | MRC IEU, University of Bristol
Co-applicants: 
Dr. Jill Demirci, Dr. Janet Catov, Dr. Mandy Schmella
Title of project: 
Impact of Breastfeeding on Cardiovascular and Metabolic Outcomes in Women with a History of Hypertensive Disorders of Pregnancy
Proposal summary: 

Women who experience a hypertensive disorder of pregnancy are at greater risk for diseases of the heart and blood vessels. Breastfeeding may reduce this risk in women in general and particularly in those who have had a hypertensive disorder of pregnancy. This proposed study will examine if the duration/amount of breastfeeding has a beneficial effect on markers of heart health in later life in women who did and did not develop a hypertensive disorder of pregnancy.

Impact of research: 
Knowledge gained from this study will provide insight into whether or not breastfeeding is cardio-protective in women with hypertensive disorders of pregnancy. If we find that breastfeeding has a cardio-protective effect in this high risk population, this could inform intervention design, policy, and breastfeeding promotion efforts among women who develop or who are at risk of developing hypertensive disorders of pregnancy
Date proposal received: 
Thursday, 26 April, 2018
Keywords: 
Epidemiology, Hypertension, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Blood pressure, BMI, Breast feeding, Cardiovascular, Nutrition - breast feeding, diet

B3106 - Does the effect of eating patterns at night on childhood weight status differ between the UK and China - 08/05/2018

B number: 
B3106
Principal applicant name: 
Kate Northstone | UoB (United Kingdom)
Co-applicants: 
Dr Sam Leary, Dr Laura Johnson, Zou Mengxuan
Title of project: 
Does the effect of eating patterns at night on childhood weight status differ between the UK and China?
Proposal summary: 

It has been suggested that night eating is related to increased fat storage and therefore increased body weight. There is also no clear definition of what is meant by night eating. The potential effects of night eating on obesity have primarily been examined in adults to date and any studies in childhood have been cross-sectional, with none in the UK. Based on information collected in diet diaries at the age of 7, this project will aim to examine different definitions of night eating and examine the effects on childhood weight status and it's change over time. This will be carried in two different cohort studies - one based in the UK and one based in China.

Impact of research: 
Potential public health advice for children around eating habits in order to help with the current obesity epidemic
Date proposal received: 
Tuesday, 1 May, 2018
Keywords: 
Epidemiology, Obesity, Statistical methods, Nutrition - breast feeding, diet

B3108 - Longitudinal patterns and predictors of multiple cancer-risk behaviours among UK adolescents - 08/05/2018

B number: 
B3108
Principal applicant name: 
Caroline Wright | BRMS University of Bristol (United Kingdom)
Co-applicants: 
Dr Ruth Kipping, Prof Rona Campbell, Matt Hickman, Jon Heron, Prof. Richard Martin
Title of project: 
Longitudinal patterns and predictors of multiple cancer-risk behaviours among UK adolescents
Proposal summary: 

Using two British cohort studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Millennium Cohort Study (MCS), this fellowship will explore the longitudinal patterns and predictors of multiple cancer-risk behaviours (MCRB). MCRB are modifiable behaviours including tobacco smoking, alcohol consumption, physical inactivity, overweight and obesity, unhealthy diet and risky sexual behaviour that are associated with cancer incidence and mortality. Rather than focusing on specific cancers this research will cover a wide range of cancers that are associated with these behaviours.

Impact of research: 
Environmental and lifestyle interventions are an important way to reduce the burden of cancers. Through the identification of subgroups of adolescents with distinct patterns of MCRB, this research will differentiate between normative and sustained risk taking. By conducting analysis with respect to cancer related adverse health outcomes at age 25 years, it will pinpoint young people at greatest risk of developing lifelong patterns of cancer-causing risk behaviours. Further, by identifying the antecedents of membership to these subgroups, it will focus prevention and intervention strategies on those at greatest risk, inform the age at which an intervention should be applied and determine whether it is universal or targeted. Creating a new measure in ALSPAC of longitudinal patterns of cancer-risk behaviours, which once derived can be used by other researchers. Multiple research outputs, including conference presentations and papers.
Date proposal received: 
Thursday, 3 May, 2018
Keywords: 
Epidemiology

B3111 - Time-dependent associations between body mass/body composition physical activity diet and lung function in childhood - 08/05/2018

B number: 
B3111
Principal applicant name: 
Annabelle Bédard | Barcelona Institute for Global Health (Spain)
Co-applicants: 
Dr Judith Garcia-Aymerich, Ms Anne-Elie Carsin
Title of project: 
Time-dependent associations between body mass/body composition, physical activity, diet and lung function in childhood
Proposal summary: 

The large increase in the prevalence of respiratory diseases over the last decades, in the West more particularly, cannot be explained by genetics only. It has been hypothesized that these increases are a consequence of changing environmental and/or lifestyle factors. Given the multifactorial aspect of these diseases, it is thus important to take into account the interrelations between these factors and respiratory health. The interrelations between body mass/body composition, physical activity, diet and lung function in childhood and adulthood have been incompletely addressed, likely because their time-dependent and bidirectional nature represent a methodologically challenging research question. Marginal structural models (MSMs) allow estimation of causal effects in observational studies by addressing time-dependent confounding (Robins JM et al. Epidemiology 2000). This approach has still limited application in respiratory epidemiology. We aim to investigate the joint and independent causal effects of body mass/body composition, physical activity and diet on lung function during childhood and early adulthood using MSMs in children from the ALSPAC study.

Impact of research: 
Respiratory diseases are global public health concerns, and leading causes of morbidity and mortality in children and adults. This research project could thus lead to potential public health interventions such as dietary, physical activity or weight loss interventions to improve lung function, prevent lung function decline etc. As per the methodological aspect of this project, we will assess the relevance of using novel methods from the causal inference framework to investigate research questions for which standard epidemiological methods are usually used and/or where knowledge is still needed. Through dissemination of its outcomes, this research project will potentially inform study design and methodology to improve causal inference when investigating specific research questions.
Date proposal received: 
Saturday, 5 May, 2018
Keywords: 
Epidemiology, Obesity, Respiratory - asthma, Statistical methods, BMI, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Nutrition - breast feeding, diet, Physical - activity, fitness, function, Statistical methods

B3113 - NIHR Bristol BRC - Exploring Mental Health and Cognition using Mendelian randomisation - 24/05/2018

B number: 
B3113
Principal applicant name: 
Robyn Wootton | University of Bristol (United Kingdom)
Co-applicants: 
Professor Marcus Munafò, Professor Ian Penton-Voak, Sarah Peters, Steph Suddell, Caroline Skirrow
Title of project: 
NIHR Bristol BRC - Exploring Mental Health and Cognition using Mendelian randomisation
Proposal summary: 

Treatment for mental illness often focuses on changing cognitive patterns (for example, cognitive behavioural therapy). There is much evidence to suggest that cognition is different in those with mental illness but whether change in cognition is a causal risk factor has not yet been established. Classic observational studies of cognitive patterns and mental illness do not get around the problems of reverse causation and residual confounding. That is to say that the change in cognition might instead emerge as a result of the mental illness, or both might be the result of other unmeasured factors.

One way to get around this is using Mendelian randomisation. Here we take genetic variants associated with the trait of interest: cognition and use them to naturally randomise individuals to levels of the exposure. Therefore, analogous to a randomised control trial, we can make conclusions about whether or not the relationship is causal. In this study, we will be looking at the cognitive traits of emotion recognition, working memory, cognitive styles and impulsivity. This research could inform the development of cognitive training tasks as interventions for mental illness.

Impact of research: 
This research could inform the development of cognitive training tasks as interventions for mental illness.
Date proposal received: 
Monday, 14 May, 2018
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, GWAS, Genetic epidemiology

B3080 - Micronutrients in Mood Disorders - 24/05/2018

B number: 
B3080
Principal applicant name: 
Richard Martin | University of Bristol
Co-applicants: 
Dr Rebecca Carnegie, Dr Jonathan Evans, Dr Giles Greene
Title of project: 
Micronutrients in Mood Disorders
Proposal summary: 

Depression and anxiety disorders are becoming increasingly common. There is some research suggesting that our diet, (what we eat) might make us more likely to become depressed and anxious. This type of research is called 'Nutritional Psychiatry' research. Many research studies have shown that people with depression and anxiety disorders do not have enough of certain 'micronutrients' either in their food, or in their blood. One example is magnesium, which is contained within green leafy vegetables, and is lacking in processed foods. It is possible that our society is not consuming enough magnesium, which could be increasing the number of people with depression and anxiety. However, it is difficult to say whether a low magnesium in depressed people was the cause of their depression. It may be because people with depression eat less healthily, or because people with other problems (alcohol use or long term illnesses) are more likely to get depressed.

This research will aim to get around these difficulties by using our DNA or genetic code to look at whether genetic changes that cause us to have lower magnesium, are also linked to us having depression.

Impact of research: 
A causative association between magnesium and depression/ anxiety would have potential public health implications, as well as provide evidence for the development of non-pharmacological interventions
Date proposal received: 
Monday, 14 May, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Nutrition - breast feeding, diet

B3118 - Genome-wide association study of anxiety and depression - 24/05/2018

B number: 
B3118
Principal applicant name: 
Nicholas Timpson | ALSPAC/IEU
Co-applicants: 
Mr Alex Kwong, Professor Cathryn Lewis, Dr John Hettema
Title of project: 
Genome-wide association study of anxiety and depression
Proposal summary: 

Genome-wide association studies (GWAS) have been instrumental in highlighting associations between genetic variants and 1000s of traits. A recent GWAS of major depressive disorder (MDD) by the psychiatric genetics consortium (PGC) has recently identified 44 genetic variants associated with the disorder (Wray et al., 2018). We plan to include ALSPAC data from the mothers and the children in the next round of analysis for both forthcoming MDD and anxiety PGC GWAS. We will prepare summary statistics from the GWAS to be shared with the PGC and perform subsequent in cohort analysis. This will be a big step towards incorporating ALSPAC data into psychiatric genetics. The summary statistics will contain no identifiable information.

Impact of research: 
These will be the largest GWAS on both MDD and anxiety disorders
Date proposal received: 
Wednesday, 23 May, 2018
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, GWAS, Genome wide association study

B3114 - Tracking Sleep Phenotypes 2 15-05-2018 - 234902 - 26/05/2018

B number: 
B3114
Principal applicant name: 
Helen Heussler | Center for CHildren's Health Research. University of Qld (Australia)
Co-applicants: 
Emily Sawyer, Prof Karen Thorpe, Simon Smith , Ronny Gunnarson, Mamun Abdullah, Enda Byrne, Adam Ewing, Peter Blair
Title of project: 
Tracking Sleep Phenotypes (2) (15-05-2018 - 23:49:02)
Proposal summary: 

Sleep matters to those who care for young children. The duration and timing of sleep can have a profound effect on a young child’s everyday behaviour, learning and health and also has a significant impact on the routines and wellbeing of the adults who provide his or her care. Yet there is surprisingly little evidence regarding the developmental function of early sleep patterns. Current understanding of the processes underpinning normative transition in sleep patterns, the prevalence of specific sleep phenotypes and persistence in sleep patterns across time is limited. This study will utilise genetic and environmental data, alongside longitudinal sleep data to examine the prevalence, persistence and developmental significance of childhood sleep phenotypes.

This knowledge will inform clinical, public health and educational policy and practice where management of sleep is an issue of controversy and also inform parenting practice where early child sleep behaviours can have a major impact on family functioning, parent well-being and child development.

Impact of research: 
The focus of our research will be important in informing care practices particularly in early childhood settings and family contexts. Internationally the importance of sleep in long term health is growing but the available evidence and subsequent evidence for policy and practice is limited. In Australia and the US for example while there are significant recommendations for exercise and nutrition in young children the existing sleep recommendations are limited to sleep safety in the first year. (We are pleased to have Prof Peter Blair on the Team) Longitudinally the existence of tight phenotypes has been challenging to establish however using this data we hope to establish some genotype- phenotype relationships to help inform practice.
Date proposal received: 
Thursday, 17 May, 2018
Keywords: 
Clinical research/clinical practice, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Mental health, DNA sequencing, GWAS, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Epigenetics, Genomics, Intelligence - memory, Sleep

B3109 - Predictive genomic classifiers for the risk assessment of common learning disabilities in children - 29/05/2018

B number: 
B3109
Principal applicant name: 
Emmanuel Labourier | Cognitive Genetics (USA)
Co-applicants: 
Dr. Dennis Wylie
Title of project: 
Predictive genomic classifiers for the risk assessment of common learning disabilities in children
Proposal summary: 

Learning disabilities are common disorders characterized by unexpected difficulty with a specific mode of learning in the context of adequate intelligence and academic opportunity. The high prevalence of these disorders in the general population represents a costly burden to the educational system and affected individual are often at risk for long-term adverse psychological and socioeconomic outcomes. Intervention programs work, but are more effective when tailored to individuals and administered earlier in life. The pre-symptomatic detection of individual who are at risk of developing learning disabilities, and who are more likely to benefit from early intervention, is therefore an important diagnostic opportunity with major economic and societal implications. The objective of this project is to evaluate the diagnostic performance and predictive value of genetic variants associated with learning disabilities in the ALSPAC cohort.

Impact of research: 
This research has the potential to improve the pre-symptomatic diagnosis of children at risk of developing learning disabilities and who may benefit from early intervention strategies
Date proposal received: 
Friday, 4 May, 2018
Keywords: 
Clinical research/clinical practice, Cognitive impairment, Learning difficulty, Speech/language problem, Computer simulations/modelling/algorithms, Cognition - cognitive function, Communication (including non-verbal), Genomics, Speech and language

B3110 - Computational Models for the Prediction and Prevention of Child Traumatic Stress - 29/05/2018

B number: 
B3110
Principal applicant name: 
Glenn Saxe | NYU Langone (USA)
Co-applicants: 
Constantin Aliferis, MD, PhD, FACMI
Title of project: 
Computational Models for the Prediction and Prevention of Child Traumatic Stress
Proposal summary: 

More than 20% of children will experience a traumatic event before they are 16 years old. Of those who experienced a trauma, a sizable minority will develop Posttraumatic Stress Disorder (PTSD), and other deleterious developmental, health, and psychiatric consequences (herein called Child Traumatic Stress). To diminish the considerable burden of traumatic stress on children and their families, the capacity to predict a child’s risk and to intervene to diminish this risk is extremely important. The literature on prediction of child traumatic stress from risk factors has yielded only modest results and - of those risk factors found to be predictive – it is difficult to determine which represent processes would lead to a diminution of risk, if effective intervention were applied. Almost certainly, traumatic stress results from a complex set of interacting bio-behavioral and social environmental processes, unfolding in specific ways over the course of development, and related to specific aspects of the traumatic exposure. Our project aims to apply state-of-the-art Machine Learning predictive modeling methods with a wide array of risk variables from the ALSPAC data set to generate reliable and accurate predictive models of PTSD and other child traumatic stress outcomes. We also aim to apply advanced non-experimental causal discovery algorithms to discover potentially remediable processes leading to traumatic stress outcomes that may reveal new opportunities for preventative intervention.

Impact of research: 
To create reliable, accurate and interpretable predictive models of child traumatic stress that can guide future research and clinical care. To discover remediable processes that influence traumatic stress and can inform the development of new and promising preventative interventions.
Date proposal received: 
Friday, 4 May, 2018
Keywords: 
Statistics/methodology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Computer simulations/modelling/algorithms, Statistical methods, Childhood - childcare, childhood adversity, Genetics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Psychology - personality

B3122 - Genome-wide analysis of selection and methylation - 06/06/2018

B number: 
B3122
Principal applicant name: 
Tom Gaunt | University of Bristol (United Kingdom)
Co-applicants: 
Ms Charlie Hatcher, Dr Santi Rodgriguez
Title of project: 
Genome-wide analysis of selection and methylation.
Proposal summary: 

Human evolution has been associated with drastic changes in environment and lifestyle over time, with each of these changes resulting in selective pressures (Voight et al., 2006). Natural selection is the differential reproductive success of genetically distinct individuals or genotypes within a population. Strongly deleterious mutations will rapidly be eliminated from populations, whereas strongly positive mutations will quickly rise to fixation leading to changes in allele frequency over time. This process leaves signatures on the genome which can then be detected (Sabeti et al., 2006).

Epigenetics refers to heritable changes outside of the DNA sequence itself and provides a potential mechanism by which environmental and lifestyle exposures can impact gene expression over the course of a lifetime. Epigenetic mechanisms can include DNA methylation and histone modifications. DNA methylation is the most widely studied epigenetic change and involves the addition of methyl groups to nucleotide bases (Vocht et al., 2018).

Natural selection is a long term, multigenerational response to environmental factors that can influence the role of genes in human traits (Bamshed and Wooding, 2003) whereas epigenetic inheritance allows stable changes in DNA methylation to be passed from one generation to the next (Feil and Fraga, 2012). Both selection and methylation act in response to environmental exposures but over different timescales. This project will aim to unravel the interplay between selection and methylation to assess whether DNA methylation offers a mechanism to respond to exposures in the short term which may eventually lead to changes in allele frequency.

References
1. Bamshad, M. & Wooding, S.P. Signatures of natural selection in the human genome. Nature Reviews Genetics 4, 99-111A (2003).
2. de Vocht, F. et al. DNA methylation from birth to late adolescence and development of multiple-risk behaviours. Journal of Affective Disorders227, 588-594 (2018).
3. Feil, R. & Fraga, M.F. Epigenetics and the environment: emerging patterns and implications. Nature Reviews Genetics 13, 97-109 (2012).
4. Sabeti, P.C. et al. Positive natural selection in the human lineage. Science 312, 1614-1620 (2006).
5. Stearns, S.C., Byars, S.G., Govindaraju, D.R. & Ewbank, D. Measuring selection in contemporary human populations (vol 11, pg 611, 2010). Nature Reviews Genetics 12, 1 (2011).
6. Voight, B.F., Kudaravalli, S., Wen, X.Q. & Pritchard, J.K. A map of recent positive selection in the human genome (vol 4, pg 154, 2006). Plos Biology 4, 659-659 (2006).

Impact of research: 
Generally, selection and methylation are assessed separately. We hope that analysing both concurrently will provide insight into the relationship between these two mechanisms and help us to better understand the impact of environmental exposures genome-wide.
Date proposal received: 
Tuesday, 29 May, 2018
Keywords: 
Genetics, Gene mapping, Statistical methods, Epigenetics, Genetic epidemiology, Genetics, Genomics, Statistical methods

B3124 - Using the power of DPUK cohorts to explore childhood adversity and adult behavioural psychological physical cognitive and b - 06/06/2018

B number: 
B3124
Principal applicant name: 
Sarah Bauermeister | University of Oxford (UK)
Co-applicants: 
Dr Kate Northstone, Dr Catherine Calvin, Ms Roise Cornish
Title of project: 
Using the power of DPUK cohorts to explore childhood adversity and adult behavioural, psychological, physical, cognitive, and, b
Proposal summary: 

Childhood adversity could cover many things including extreme difficulties and adverse experiences during childhood such as sexual, physical and emotional abuse, deprivation, and family dysfunction. Experiencing adversity during childhood may have a dramatic effect on a child's life. It has been linked to a number of poor outcomes in adulthood such as worse health outcomes, poor mental health, reduced life satisfaction and dementia. One in three adults diagnosed with mental health conditions are reported to have experienced childhood adversities therefore, there is the potential for life-long associations between childhood adversity and health, which need to be evaluated and accounted for. The proposed project will examine childhood adversity in three different UK populations and in a birth cohort and associations with a number of different outcomes including physica and mental health, poor lifestyle choice such as unhealthy diet, smoking and binge drinking and antisocial behaviours.

Impact of research: 
One-in-three adult mental and physical health conditions are attributed directly to adverse childhood experiences and trauma. Furthermore, adversity in younger life may lead to adverse adult behaviours and premature mortality. This proposal is of utmost public benefit, highlighting the importance of understanding the implications of childhood adversity on adult behavioural, psychological, cognitive and health outcomes. Only through understanding the pathway mechanisms and implications will there be hope of policy changes regarding increased funding towards preventative strategies and resourcing earlier interventions to prevent childhood adversity. Moreover, understanding the causal effects of adverse adult outcomes is of equal importance as we economically manage an increasing ageing population with comorbid disorders and overall decline.
Date proposal received: 
Tuesday, 29 May, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Childhood - childcare, childhood adversity

B3125 - Trajectories of Weight and Obesity From Birth to Adulthood According to Polygenic Susceptibility - 06/06/2018

B number: 
B3125
Principal applicant name: 
Kaitlin Wade | MRC-IEU (United Kingdom)
Co-applicants: 
Title of project: 
Trajectories of Weight and Obesity From Birth to Adulthood According to Polygenic Susceptibility
Proposal summary: 

We want to quantify what the impact of genetics across the whole genome has on weight and risk of severe obesity from birth to middle adulthood.

Impact of research: 
We may determine whether inborn polygenic susceptibility to increased weight and severe obesity manifests itself starting in early childhood and has substantial impact extending into middle age.
Date proposal received: 
Wednesday, 30 May, 2018
Keywords: 
Genetics, Obesity, GWAS, Statistical methods, BMI, Childhood - childcare, childhood adversity, Genetics

B3127 - Maternal caffeine intake during pregnancy An epigenome-wide association study - 06/06/2018

B number: 
B3127
Principal applicant name: 
Gemma Sharp | IEU, University of Bristol (UK)
Co-applicants: 
Miss Laura Schellhas
Title of project: 
Maternal caffeine intake during pregnancy: An epigenome-wide association study
Proposal summary: 

Rationale: Animal studies have provided some evidence that maternal caffeine consumption can influence offspring DNA methylation (PMIDs: 22970234, 24475304, 25354728, 25868845, 25868845), but what about humans?

Impact of research: 
Clarifying the association of caffeine intake during pregnancy and offspring methylation at birth in humans
Date proposal received: 
Friday, 1 June, 2018
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., epigenome-wide association study, Biological samples -e.g. blood, cell lines, saliva, etc., Birth outcomes, Development, Epigenetics, Genetic epidemiology, Genetics, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Offspring

B3129 - Longitudinal intake of free sugars in ALSPAC children 06-06-2018 - 151010 - 06/06/2018

B number: 
B3129
Principal applicant name: 
Pauline Emmett | CCAH, University of Bristol (United Kingdom)
Co-applicants: 
Dr Caroline Taylor
Title of project: 
Longitudinal intake of free sugars in ALSPAC children (06-06-2018 - 15:10:10)
Proposal summary: 

The current recommendation is that we should limit our intake of free sugars to provide less than 10% of daily energy intake. This study will investigate free sugars intake in ALSPAC children at ages 18 months, 3.5, 5, 7, 10 & 13 years and determine whether those consuming less than 10% energy from free sugars have a more beneficial nutrient and food group intake than those that consuming more free sugars. Then to investigate if there are differences in obesity levels in relation to free sugars intakes.

Impact of research: 
This is extremely topical and will contribute to an current EFSA review
Date proposal received: 
Wednesday, 6 June, 2018
Keywords: 
Nutrition, Diabetes, Statistical methods, Nutrition - breast feeding, diet

B3132 - Genetic and epigenetic variation in the newborn brain in relation to neurodevelopmental outcomes in childhood - 14/06/2018

B number: 
B3132
Principal applicant name: 
Santi Rodriguez | Integrative Epidemiology Unit, Bristol Medical School (UK)
Co-applicants: 
Dr Karen Luyt, Dr David Odd, Silvia Pregnolato, Emily Jamieson
Title of project: 
Genetic and epigenetic variation in the newborn brain in relation to neurodevelopmental outcomes in childhood
Proposal summary: 

This study aims at exploring the possible influence of genetic and epigenetic variants in the newborn brain on neurologic and mental traits and outcomes. This project aims to combine research from the Bristol Neonatal Gene Study and from ALSPAC. This will represent an interesting opportunity to study in detail the effect of specific genetic and epigenetic variants both in newborns and in childhood. We specifically aim to study the main candidate pathways involved in perinatal brain injuries (glutamate signalling and inflammation) and long-term motor, cognitive and behavioural outcomes. We have produced interesting preliminary findings within the Bristol Neonatal Gene Study, which support the involvement of candidate genetic variants in the glutamate signalling and inflammation pathways. The ALSPAC cohort provides a unique opportunity to validate and add to these findings in a large sample with genetic, epigenetic and phenotypic data collected longitudinally from birth to childhood. With the availability of maternal data, it also offers the opportunity to expand the analysis to maternal-neonatal gene-gene and gene-environment interactions. We have the appropriate expertise in genetic and epigenetic research required for this project. In addition, we are coupling this approach with in vivo work on animal models of newborn brain injuries, exploring the (dys)regulation of key genes involved in glutamate transport and inflammation during perinatal insults.

Impact of research: 
Genetic and epigenetic biomarkers may provide invaluable tools to predict the risk of brain injuries at birth and potentially long before the onset of labour. They may also provide a tool to identify babies who are more likely to respond to treatment, both in the short- and long-term. Both glutamate signalling and inflammation are ideal candidates for a pharmacogenomics approach for existing and novel drugs targeting these pathways. The study may also generate hypotheses about manipulating DNA methylation to achieve neuroprotection. We expect that through a better understanding of the molecular mechanisms of injury it will be possible to improve early identification, diagnosis and treatment, ultimately providing a better prognosis for these newborns. This is likely to help mothers, families and clinicians making more informed and personalised decisions when planning pregnancy, childbirth and child follow-up, contributing to the push of neonatal care towards prediction and prevention.
Date proposal received: 
Tuesday, 12 June, 2018
Keywords: 
Genetics, Neurodevelopmental outcomes in childhood, Gene mapping, GWAS, Statistical methods, Cognition - cognitive function, Epigenetics, Genetic epidemiology, Genetics, Genome wide association study, Mendelian randomisation, Neurology, Statistical methods

B3133 - Exploring the longitudinal effect of early maturation on physical and mental wellbeing - 14/06/2018

B number: 
B3133
Principal applicant name: 
Fiona Gillison | University of Bath (United Kingdom)
Co-applicants: 
Dr Sean Cumming, Dr Lauren Sherar, Ms Irma Fehratovic
Title of project: 
Exploring the longitudinal effect of early maturation on physical and mental wellbeing
Proposal summary: 

Research suggests that children who reach puberty early are at risk of poorer health and wellbeing. Such ‘early maturing’ children also tend to take part in riskier health behaviours, such as smoking, drinking alcohol and risky sexual activity. However, most studies look at these links at a single point in time, which limits how confident we can be that early maturing causes poorer wellbeing. Few studies have looked at what factors may increase or decrease some of these risks. Our study aims to use the ALSPAC data explore three questions relating to the longer-term health risks of adolescents who mature early. The first builds on work we have done with parents, showing many believe we should judge whether or not a child is overweight differently if they are an early maturer, to avoid labeling them as overweight when they are not. This is a particularly important time to consider how we respond to children's weights, as it is the point at which over 95% of children in England are weighed and measured as part of the National Child Measurement Programme. Some parents have been strong critics of this process, so public health teams and parents alike are interested in exploring how we could interpret and use this information better. To explore whether it is appropriate to use the same means of classifying early and on-time maturers as overweight, we will apply an adjustment for maturity to our calculations of weight status for children at age 11, and explore whether this is a better way of predicting which children will have higher/lower future health risks at age 17 (including obesity, blood pressure and other risk factors). Second, we will compare which factor at at age 10/11 is the stronger predictor of wellbeing in later adolescence; being overweight, or maturing early. Finally, to explore what factors might help children to avoid some of the potential consequences of maturing early, we will look at whether children’s views of the strength and importance of their relationships with parents and peers influence the effect of being an early maturer on their wellbeing by the age of 17 (including depression, positive wellbeing, and risk behaviours such as smoking and drinking).

Impact of research: 
This study will contribute to an increasing body of work exploring how we should use NCMP data being undertaken by the lead investigator. Depending on the findings, it will inform future funding applications and work with policy makers (namely PHE in the first instance) aiming to find better ways of engaging with parents of overweight children in ways that are meaningful to them to help children to maintain a healthy weight in childhood, and experience subsequent benefits to their physical and mental health. It will provide a case study of how we can learn from one field to apply it to another (e.g., applying Dr Cumming's work on biobanding to relevant health settings), developing our understanding of the more individual health and health-preventive needs of adolescents.
Date proposal received: 
Wednesday, 13 June, 2018
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Obesity, Statistical methods, BMI, Development, Psychology - personality, Physical - activity, fitness, function, Puberty, Sex differences, Social science

B3554 - Asthma and COVID-19 - 08/06/2020

B number: 
B3554
Principal applicant name: 
Raquel Granell | MRC Integrative Epidemiology Unit (IEU) Population Health Sciences (United Kingdom)
Co-applicants: 
Dr James Dodd
Title of project: 
Asthma and COVID-19
Proposal summary: 

Asthma affects the lives of 5.4 million people across the UK. COVID-19 attacks the lungs and can trigger asthma symptoms like wheezing, chest tightness and difficulty breathing, which is very distressing for patients and can cause feelings of anxiety. We want to know if participants with asthma at 23-24 years were more likely to report respiratory symptoms, mental health issues, shielding during the COVID-19 lock-down.

We'll also be interested to explore differences between people with asthma and COVID-19 related symptoms and people with asthma and non-related COVID-19 symptoms, e.g. economical status, asthma severity....

Impact of research: 
Date proposal received: 
Friday, 5 June, 2020
Keywords: 
Epidemiology

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