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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B2819 - Markers of prediabetes psychotic experiences and inflammation A cohort study from ALSPAC - 2017/19/01

B number: 
B2819
Principal applicant name: 
Benjamin Ian Perry | 1) Coventry and Warwickshire Partnership NHS Trust 2) Department of Mental Health and Wellbeing, University of Warwick (UK)
Co-applicants: 
Dr Rachel Upthegrove, Dr Andrew Thompson, Dr Steven Marwaha, Dr Golam Khandaker, Professor Stan Zammit
Title of project: 
Markers of prediabetes, psychotic experiences and inflammation: A cohort study from ALSPAC
Proposal summary: 

Patients with schizophrenia have shortened life expectancy, with mortality rates twice that of the general population. Causes for this extend beyond suicide, accidents and risk-taking behaviour. Research indicates that physical illnesses, including heart disease and type 2 diabetes mellitus (T2DM) account for a majority of the increased mortality risk. The prevalence of T2DM in schizophrenia is increased by around one-third compared with the general population.

There is a growing body of research to suggest that links between the two illnesses may go deeper than the previously assumed - related solely due to either a side-effect of medications used to treat schizophrenia, reduced access to healthcare in patients with schizophrenia, and poor diet/sedentary lifestyle. A recent meta-analysis in Lancet Psychiatry by the lead proposal author has shown that participants with first-episode psychosis (the first time a generally younger person goes to hospital with symptoms of schizophrenia) are more likely to have signs of early diabetes than healthy matched controls. All participants in the meta-analysis had very limited exposure to antipsychotic medication, reducing the impact of the potential confounder.

There is a growing body of work showing that both schizophrenia and diabetes may indeed feature an inflammatory component, and this may be shared. The inflammatory component in patients with a potentially earlier form of schizophrenia - termed 'psychotic experiences', has previously been examined in the ALSPAC cohort by one of the proposal authors, with positive findings.

It would therefore be of great interest to examine whether any possible disease link begins earlier than the 'first psychotic episode', by examining patients suffering 'psychotic experiences'. With the noted possible inflammatory disease links between diabetes and schizophrenia, it would be of great interest to examine whether those with psychotic experiences and abnormal inflammatory profiles also have abnormal glycaemic indices.

Finally, it would be interesting to examine whether markers of early diabetes can predict the onset of psychotic experiences.

Impact of research: 
This research has the potential to further shape our knowledge of the intrinsic disease links between psychotic illness and dysglycaemia. It may help to define a subset of patients at risk of psychosis with abnormal glycaemic indices and perhaps inflammatory markers, in future for whom targeted treatments may be possible.
Date proposal received: 
Saturday, 14 January, 2017
Date proposal approved: 
Thursday, 19 January, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Diabetes, Mental health, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Cohort studies - attrition, bias, participant engagement, ethics, Endocrine - endocrine disrupters, Hormones - cortisol, IGF, thyroid, Immunity, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B2820 - Is Endothelial Function Involved in Stroke and Dementia - 2017/19/01

B number: 
B2820
Principal applicant name: 
Matthew Traylor | University of Cambridge (United Kingdom)
Co-applicants: 
Professor Hugh Markus
Title of project: 
Is Endothelial Function Involved in Stroke and Dementia?
Proposal summary: 

This project is part of a larger EU-funded funded project (CoSTREAM), aimed at identifying shared mechanisms which lead to both stroke and Alzheimer's Disease. One such mechanism we are investigating is endothelial function – the normal response of vessels to being supplied with blood. In this project, we aim to test whether changes in endothelial function are involved in Alzheimer's Disease and stroke. We plan to do this by testing whether genetic factors that alter endothelial function also influence risk of Alzheimer's Disease and stroke.

Impact of research: 
Our research will test directly whether a specific pathway (endothelial function) is involved in risk of stroke and dementia. This will help to direct treatment approaches and help to build on evidence that vascular factors are implicated in pathogenesis of Alzheimer's Disease.
Date proposal received: 
Monday, 16 January, 2017
Date proposal approved: 
Thursday, 19 January, 2017
Keywords: 
Genetics, Cognitive impairment, GWAS, Mendelian Randomization Polygenic Risk Scoring, Ageing, Cardiovascular, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B2822 - The role of genetics and biology in the aetiology of self-harm - 2017/19/01

B number: 
B2822
Principal applicant name: 
Becky Mars | University of Bristol
Co-applicants: 
Professor David Gunnell, Dr Jon Heron, Dr Carol Joinson, Dr Paul Moran, Dr Matthew Suderman, Dr Gibran Hemani, Professor Caroline Relton, Professor Tamsin Ford
Title of project: 
The role of genetics and biology in the aetiology of self-harm
Proposal summary: 

Self-harm in young people is a major public health concern. Recent community studies indicate that up to 1 in 6 adolescents have self-harmed at some point in their lives, with the incidence rising rapidly between 10 and 16 years of age. Self-harm is distressing for individuals, their friends, families, and carers, and is associated with a range of poor outcomes in early adulthood. It is also the strongest known risk factor for suicide. Although self-harm is very common in adolescence, we know little about what causes this behaviour. A better understanding of the factors that increase the risk for self-harm, and the mechanisms through which they operate is important in order to develop more effective treatments.
Many previous studies have identified early life adversity (such as physical abuse, sexual abuse, and emotional neglect) as an important risk factor for self-harm. However we don’t yet understand how exposure to adversity can trigger later self-harm behaviour. It is known that the social environment can have an impact on internal biological processes. This is of interest as there is growing evidence to suggest that biological factors are involved in suicide and self-harm. We aim to study whether experiences of early adversity are associated with three different biological processes (inflammation, onset of puberty, and DNA methylation) and explore whether these factors are, in turn, associated with self-harm in adolescence. This work can provide a model whereby early adversity can lead to self-harm through biological pathways. This could lead to identification of potential markers of future self-harm risk, as well as possible targets for treatment, and interventions to prevent people from developing self-harm. In order to investigate these pathways, it is necessary to establish the order in which events occur. To do this requires a large sample with information collected at multiple time points from childhood to adolescence. Our research will also investigate whether associations between inflammation, puberty, DNA methylation and self-harm are causal, or whether they might be explained by other factors (known as confounding).
To date, most studies of self-harm in adolescence have been based on small clinical samples – these are highly select groups, already known to medical services. In addition, existing studies have tended to focus only on suicide attempts, but only one quarter of self-harm episodes are carried out with expressed suicidal intent. An important question is whether suicidal and non-suicidal self-harm are distinct behaviours, or part of a continuum of risk. Previous studies have explored whether there are differences in risk-factors and outcomes for these behaviours. We aim to extend this work by providing new information about whether there are differences in their genetic architecture. This work will inform future research studies of self-harm, and help to inform decisions on how self-harm should be defined.

Impact of research: 
Our findings could lead to the identification of potential biomarkers of self-harm risk, and also to the development of novel approaches to the detection, treatment and prevention of self-harm. This will, in turn, inform future translational research and benefit academics involved in developing and trialling interventions for the prevention and treatment of self-harm The UK and International research and mental health policy communities will benefit from a stronger evidence base concerning the distinction between self-harm with and without suicidal intent. This project will provide new information regarding the value of this distinction, and in particular, whether the distinction has a meaningful biological basis. As such, the findings are likely to be highly informative for future revisions of the Diagnostic and Statistical Manual (DSM) and International Classification of Diseases (ICD).
Date proposal received: 
Tuesday, 17 January, 2017
Date proposal approved: 
Thursday, 19 January, 2017
Keywords: 
Epidemiology, self-harm, Epigenetics, GWAS, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Puberty

B2818 - A methylation-based biomarker for alcohol intake in the general population - 2017/19/01

B number: 
B2818
Principal applicant name: 
Paul Yousefi | MRC Integrative Epidemiology Unit, University of Bristol (United Kingdom)
Co-applicants: 
Dr. Luisa Zuccolo , Dr. Matthew Suderman
Title of project: 
A methylation-based biomarker for alcohol intake in the general population
Proposal summary: 

A recent study by Liu et al (http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016192a.html) developed an accurate biomarker of alcohol intake, using the levels of DNA methylation at 144 CpG sites. Such a biomarker has the potential to provide a more reliable estimate of alcohol use in future studies. As self-reported alcohol intake may be bias or otherwise unreliable, such a biomarker may serve as a valuable supplement to self-reported data, especially in epidemiological studies where careful estimation of alcohol use is needed.

We seek to validate this alcohol intake biomarker in an independent cohort, and rigorously assess its performance and modeling assumptions. Further, we'll seek to extend it's application to predictions across the life-course.

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: 
Friday, 13 January, 2017
Date proposal approved: 
Thursday, 19 January, 2017
Keywords: 
Epidemiology

B2816 - Global lipids genetic consortium metabolomics - 2017/13/01

B number: 
B2816
Principal applicant name: 
Fotios Drenos | (United Kingdom)
Co-applicants: 
Title of project: 
Global lipids genetic consortium metabolomics
Proposal summary: 

Dyslipidemia is a common disorder associated with abnormal lipid levels, usually elevated, commonly associated with the risk of a cardiovascular event. Our understanding of the genetics of the disease relies mainly on common polymorphisms affecting the levels of proteins involved in lipids metabolism. In contrast, changes in the areas of the genome containing the information for the building blocks of proteins can alter the structure and function of these proteins. These DNA changes tend to be less common in the genome and currently we are only aware of a small number of them associated with lipids associated disorders, some of them severe.

The largest consortium of scientists working on the genetics of plasma lipids, the Global Lipids Genetic Consortium (GLGC), has recently used more than 300,000 individuals to study these protein changing mutations and identified a number of them both in novel and previously reported areas of the genome as associated with one or more of the four main measured lipids traits: high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and total cholesterol levels. These four commonly measured lipids traits though, are groupings of other lipids subfractions that can have very different compositions and properties not evident in the overall grouping, thus making the understanding of the specific action of the gene of interest difficult. Although we can sometimes infer the action of the genes through model organisms or laboratory experiments, these are not always accurate representations of how things work in the human body.

Impact of research: 
Functional characterisation of novel and established lipids associated variants and identification of dyslipidemia subtypes
Date proposal received: 
Friday, 6 January, 2017
Date proposal approved: 
Friday, 13 January, 2017
Keywords: 
Genetics

B2790 - Maternal prepregnancy BMI gestational weight gain and risk of offspring ASD in the ALSPAC birth cohort - 2017/09/01

B number: 
B2790
Principal applicant name: 
Brian K Lee | Drexel University (United States)
Co-applicants: 
Dr. Nora L Lee, Dr. Dheeraj Rai, Xi Wang
Title of project: 
Maternal prepregnancy BMI, gestational weight gain, and risk of offspring ASD in the ALSPAC birth cohort
Proposal summary: 

Prevalence estimate of the autism spectrum disorders (ASD) has significantly increased over the decades. Maternal body mass index (BMI) prior to pregnancy and gestational weight gain (GWG) have attracted attention as potential risk factors for offspring ASD, given noticeable increase in the prevalence of prepregnancy obesity and high prevalence of inappropriate GWG in recent years.

The project will examine the effects of maternal prepregnancy BMI and GWG on ASD among offspring, and explore the underlying mechanism. Our hypotheses are that prepregnancy obesity and inadequate/excessive GWG are associated with increased risk for offspring ASD and that adverse obstetric outcomes account for part of these effects.

If our hypotheses are supported, this project will shed light into the environmental base of ASD and aid in the development of preventative strategies. Moreover, with underlying pathways understood, interventions can be applied on the modifiable mediators.

Impact of research: 
The identification of prepregnancy BMI and GWG as risk factors will shed light on the environmental base of ASD and aid in the development of preventative strategies. If our hypotheses are supported, the study results will be publicized to inform women at the childbearing age of the importance of conceiving at a normal weight and to inform antenatal care practice of the importance of assisting pregnant women to gain appropriate weight. Moreover, with underlying pathways understood, interventions can be applied on the modifiable mediators among the high-risk obese mothers.
Date proposal received: 
Friday, 18 November, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Epidemiology, Developmental disorders - autism, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Birth outcomes, BMI, Mothers - maternal age, menopause, obstetrics, Statistical methods

B2804 - Pathways from childhood victimisation to anxiety and depression in early adulthood - 2017/09/01

B number: 
B2804
Principal applicant name: 
Belinda Graham | University of Oxford (UK)
Co-applicants: 
Dr Lucy Bowes
Title of project: 
Pathways from childhood victimisation to anxiety and depression in early adulthood.
Proposal summary: 

Victimisation in childhood and adolescence is associated with increased risk of adult mental health problems, including anxiety and depression. However, mechanisms and causal pathways underlying the association with clinical anxiety and depression are not fully understood. Based on cognitive theory of anxiety disorders and trauma, this project will explore cognitive and behavioural factors at an individual and interpersonal level that might maintain negative effects of bullying. These prospective analyses will help differentiate those who recover after bullying from those who do not, and inform specific new targets for psychological interventions to help those who suffer clinical anxiety and depression after being bullied.

Impact of research: 
We expect that findings from these analyses will help inform new clinical psychological interventions for young people and adults who are suffering with anxiety related to experiences of bullying. We intend to present findings in relevant scientific and applied conferences, and to publish in peer-reviewed journals. These analyses will also fulfil part of the requirements for the first author’s DPhil in clinical research, developing specialist psychological interventions for people who suffer anxiety and depression related to bullying.
Date proposal received: 
Friday, 9 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Psychology - personality, Bullying, Victimization

B2805 - Residential exposure to radon and DNA methylation across the lifecourse - 2017/09/01

B number: 
B2805
Principal applicant name: 
Frank de Vocht | SSCM (UK)
Co-applicants: 
Professor Kate Tilling, Professor Caroline Relton, Dr Matthew Suderman, Andrew Boyd, Prof Alberto Ruano-Ravina, Professor Richard Wakeford
Title of project: 
Residential exposure to radon and DNA methylation across the lifecourse
Proposal summary: 

Radon is a colourless, odorless and tasteless gas that occurs naturally in rocks and water. It is also a radioactive decay product of radium. Inhaled radon gas is the main contributer to ionizing radiation in the general population. Although it occurs naturally, this differs depending on the make-up of soil while it can also accumulate in buildings (especially in low areas). Epidemiology has shown a clear link between radon gas exposure and lung cancer risk, including in non-smokers, and is considered the second most frequent cause of lung cancer (after cigarette smoking). In this project we, for the first time, will explore whether there is any evidence of epigenetic (DNA methylation) signals as a result of residential exposure to radon that can already be measured at young age (well before the development of lung cancer) and whether any signal could be dose-dependent. If there is evidence of such an association in ALSPAC, and given the ubiquitous exposure but also straightforward methods for interventions to improve the indoor environment, this project may result in (a) updated advice on hazards of radon exposure across the lifecourse and (b) a grant application to investigate this in a much larger cohort, such as the pooled cohorts in the CLOSER consortium), to provide more robust estimates of risk.

Impact of research: 
The likely impact of this hypothesis-generating project are expected to be (in addition to a peer-reviewed publication): (a) updated advice on hazards of radon exposure across the lifecourse and (b) a grant application to investigate this in a much larger cohort, such as the pooled cohorts in the CLOSER consortium), to provide more robust estimates of risk.
Date proposal received: 
Wednesday, 14 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Epidemiology, Cancer, DNA methylation, Epigenetics, Biological samples -e.g. blood, cell lines, saliva, etc., Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Linkage

B2806 - Behavioural susceptibility to obesity in young adults genetic and environmental determinants of eating behaviour - 2017/09/01

B number: 
B2806
Principal applicant name: 
Manos Magklis | Center for Exercise, Nutrition and Health Sciences, School of Policy Studies, University of Bristol, Bristol, United Kingdom (United Kingdom)
Co-applicants: 
Title of project: 
Behavioural susceptibility to obesity in young adults: genetic and environmental determinants of eating behaviour
Proposal summary: 

More and more people are facing health problems because of a body weight that is too high.
Eating more than really needed can lead to weight gain and, for some, avoiding overeating is particularly difficult. With this study, we want to figure out the many reasons behind this ‘difficulty’ (both genetic and non-genetic) and hope to inform more appropriate actions.

Impact of research: 
Understanding of the mechanisms through which a series of genetic and environmental determinants affect appetitive traits and, ultimately, body weight. This is expected to lead to more effective obesity prevention and treatment interventions that will be informed by individuals’ behavioural susceptibility.
Date proposal received: 
Thursday, 15 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, Computer simulations/modelling/algorithms, Gene expression, Gene mapping, Genomics - structural variants, GWAS, Statistical methods, Psychometrics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Growth, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Microbiome, Nutrition - breast feeding, diet, Offspring, Parenting, Psychology - personality, Physical - activity, fitness, function, Blood pressure, Puberty, Sex differences, Siblings, Sleep, Social science, Statistical methods, Twins, BMI, Breast feeding, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Development, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2806 - Behavioural susceptibility to obesity in young adults genetic and environmental determinants of eating behaviour - 2017/09/01

B number: 
B2806
Principal applicant name: 
Manos Magklis | Center for Exercise, Nutrition and Health Sciences, School of Policy Studies, University of Bristol, Bristol, United Kingdom (United Kingdom)
Co-applicants: 
Title of project: 
Behavioural susceptibility to obesity in young adults: genetic and environmental determinants of eating behaviour
Proposal summary: 

More and more people are facing health problems because of a body weight that is too high.
Eating more than really needed can lead to weight gain and, for some, avoiding overeating is particularly difficult. With this study, we want to figure out the many reasons behind this ‘difficulty’ (both genetic and non-genetic) and hope to inform more appropriate actions.

Impact of research: 
Understanding of the mechanisms through which a series of genetic and environmental determinants affect appetitive traits and, ultimately, body weight. This is expected to lead to more effective obesity prevention and treatment interventions that will be informed by individuals’ behavioural susceptibility.
Date proposal received: 
Thursday, 15 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Obesity, Computer simulations/modelling/algorithms, Gene expression, Gene mapping, Genomics - structural variants, GWAS, Statistical methods, Psychometrics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Growth, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Microbiome, Nutrition - breast feeding, diet, Offspring, Parenting, Psychology - personality, Physical - activity, fitness, function, Blood pressure, Puberty, Sex differences, Siblings, Sleep, Social science, Statistical methods, Twins, BMI, Breast feeding, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Development, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2808 - DNA methylation networks epigenetic changes during development across generations and with environmental exposures - 2017/09/01

B number: 
B2808
Principal applicant name: 
Sarah H Watkins | IEU, School of Social and Community Medicine, University of Bristol (UK)
Co-applicants: 
Dr Tom Gaunt, Dr Josine Min, Dr Nic Timpson
Title of project: 
DNA methylation networks: epigenetic changes during development, across generations, and with environmental exposures
Proposal summary: 

DNA methylation is a chemical change to our DNA that can determine whether a gene is expressed or not. We know DNA methylation changes naturally as we age, and we also know that it can change in response to the environment. This project will describe these changes in methylation data from the ALSPAC cohort. We will then look at how DNA methylation differs between children and their mothers, and how methylation changes as they age. I will also look at how aspects of the environment, such as smoking and diet, can change patterns of methylation, and whether these changes are the same or different across generations.

Impact of research: 
I hope it will identify the contribution of DNA methylation to normal development, and illustrate the extent to which DNA methylation changes over time. I also hope it may illustrate how DNA methylation is involved in disease and how it changes over time in response to the environment. This would inform future research about how DNA methylation changes normally, and so the impact is likely to be primarily within the scientific community.
Date proposal received: 
Friday, 16 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Bioinformatics, Epigenetics, Microarrays, Statistical methods, Ageing, Development, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B2811 - Gene-environment analysis in eczema - 2017/09/01

B number: 
B2811
Principal applicant name: 
Lavinia Paternoster | MRC IEU (United Kingdom)
Co-applicants: 
Miss Helena Blakeway
Title of project: 
Gene-environment analysis in eczema
Proposal summary: 

The rapid rise in prevalence of eczema within the industrialised world illustrates the importance of environmental factors in aetiology, but the precise nature and mechanisms of action of these factors remains unclear. Genetic studies have identified key mechanisms in eczema predisposition and the interaction of genetic risk with environmental factor (GxE or G*E) is likely to account for a proportion of the observed rise in prevalence. This provides an opportunity to identify key environmental factors.

We propose to use existing datasets (including ALSPAC) to investigate interactions between the genetic risk loci and selected environmental factors.

Impact of research: 
Improve understanding of eczema aetiology.
Date proposal received: 
Tuesday, 20 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Genetics, Eczema, Statistical methods, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2815 - Comparison of polygenic risk scores across cohorts 06-01-2017 - 110415 - 2017/09/01

B number: 
B2815
Principal applicant name: 
Kate Tilling | IEU,SSCM, UoB (United Kingdom)
Co-applicants: 
Professor George Davey Smith, Marcus Munafo, Dr. Amy Taylor, Dr. Neil Davies, Dr Hannah Jones, Dr Evie Stergiakouli, Dr. Hannah Sallis, Dr. Eleanor Sanderson
Title of project: 
Comparison of polygenic risk scores across cohorts (06-01-2017 - 11:04:15)
Proposal summary: 

Members of the ALSPAC cohort (mothers, fathers and their offspring) have been followed up for almost 25 years through regular questionnaires and clinics. ALSPAC aimed to recruit all eligible mothers during their pregnancy – however, there may be some differences between participating and non-participating mothers in terms of social and lifestyle characteristics. Other studies which are used in medical research may be less representative of the general population, and this may lead to biased results. However, for each study, it is hard to identify differences between those who participate and those who don’t, as we only have information on those who participate. In this research we will use genetic variants that are associated with lifestyle factors, for example, education, body mass index and smoking, to assess whether the distributions of each of these factors differ between participants in the ALSPAC study and participants in other studies which may be less representative of the general population. We will also examine differences between participants in ALSPAC and participants in the ARIES substudy, where we know some of the lifestyle factors which differ between these two groups. Understanding whether we can identify factors related to participation from genetic data collected on participants will help researchers to obtain correct results in ALSPAC and in other cohort studies.

Impact of research: 
Exploring genetic determinants of participation in ALSPAC and other cohort studies should help to determine factors which cause participation. This should inform strategies for improving participation in longitudinal studies and methods for reducing bias due to selection in analyses of cohort studies.
Date proposal received: 
Friday, 6 January, 2017
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Statistics/methodology, Cohort studies - attrition, bias, participant engagement, ethics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods

B2803 - Intergenerational transmission of health and well-being The role of psychological well-being as a mediator for the socioeconomi - 2017/09/01

B number: 
B2803
Principal applicant name: 
Simone Ghislandi | Vienna University of Economics and Business (WU) (Austria)
Co-applicants: 
Daniela Weber, Mujaheed Shaikh, Anna Renner
Title of project: 
Intergenerational transmission of health and well-being. The role of psychological well-being as a mediator for the socioeconomi
Proposal summary: 

The project we propose aims to follow individual well-being and health over the early stage of life and trace out their consequences on future outcomes. Considering parents and family health and socioeconomic background at birth and genetics as the starting conditions of a dynamic system, we take a life course perspective and analyze the mechanisms through which the socioeconomic dimension can influence the pathways of child development. Our approach considers the psychological well-being as a socioeconomic-related mediating factor that exerts its influence since the early stages of one’s life, in turn affecting the development pathways.

Impact of research: 
Scientifically: 1. To disentangle the role of psychological well-being in explaining certain cognitive outcomes and health behaviours. 2. To understand to what extent this dimension is a "given" for the child (through genetics or through intergenerational transmission of relevant characteristics). 3. The timing of the divergent pathways in the cognitive and behavioral outcomes. The impact of the research can potentially go beyond the publication of scientific papers. Knowing the role of psychological well-being, the sources and the timing of stress exposure should help shaping appropriate preventive policies, targeting the right vulnerable groups at the right stage of life.
Date proposal received: 
Monday, 5 December, 2016
Date proposal approved: 
Monday, 9 January, 2017
Keywords: 
Social Science, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cognitive impairment, Diabetes, Hypertension, Mental health, Statistical methods, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Intelligence - memory, Psychology - personality, Sleep, Social science

B2800 - Are effects of early-life oxidant exposures on asthma risk modified by TRPA1 variants and mediated by TRPA1 methylation - 2016/05/12

B number: 
B2800
Principal applicant name: 
Seif Shaheen | Barts and The London School of Medicine and Dentistry, Queen Mary University of London (UK)
Co-applicants: 
John Henderson, Caroline Relton, Annabelle Bedard
Title of project: 
Are effects of early-life oxidant exposures on asthma risk modified by TRPA1 variants and mediated by TRPA1 methylation?
Proposal summary: 

In the UK asthma is the commonest chronic illness of children, but attempts to prevent childhood asthma have been largely unsuccessful. Epidemiological studies have suggested that exposure of a child before and after birth to tobacco smoke and air pollution increases their risk of developing asthma. A low consumption of fruit and vegetables and antioxidant vitamins (vitamins C, E and A) early in life may also increase risk. In the ALSPAC study we recently discovered that children with particular types of a gene called TRPA1 were more likely than children with other types of the gene to develop asthma. The TRPA1 gene controls a protein which is thought to increase inflammation of the airways in asthma, and the action of this protein is increased by harmful substances in the environment, such as tobacco smoke and air pollution.
We believe that children with ‘risky’ forms of the TRPA1 gene may be more likely than other children to develop asthma when they are exposed early in life to tobacco smoke and air pollution, or if their intake of protective antioxidants (from fruit, vegetables and vitamins) is low. We plan to test this hypothesis by analysing existing data in ALSPAC. In a subset of ALSPAC mothers and children we will also explore whether the risk of developing asthma partly depends on whether the TRPA1 gene is turned on or off. We will do this by measuring how much the DNA in the TRPA1 gene is chemically altered by a process called 'methylation'. Exposure to pollutants can alter the level of DNA methylation and this, in turn, can influence the extent to which a gene is turned on or off.
If we can confirm that infants who carry ‘risky’ forms of the TRPA1 gene are more likely to develop later asthma when exposed to harmful pollutants or a poor diet, this could help us to find ways to prevent childhood asthma from developing in the first place in these vulnerable individuals. For example, infants who are genetically susceptible in this way might particularly benefit from taking antioxidant vitamin supplements or from strategies designed to reduce their exposure to air pollution.

Impact of research: 
Deeper understanding of the potential role of TRPA1 in the aetiology of asthma and the mechanisms by which established early life risk factors might influence the development of asthma.
Date proposal received: 
Thursday, 1 December, 2016
Date proposal approved: 
Monday, 5 December, 2016
Keywords: 
Epidemiology, Allergy, Eczema, Respiratory - asthma, Epigenetics, GWAS, Statistical methods, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2801 - Effects of puberty timing on the metabolome - 2016/05/12

B number: 
B2801
Principal applicant name: 
Joshua Bell | IEU, University of Bristol (UK)
Co-applicants: 
Prof George Davey Smith
Title of project: 
Effects of puberty timing on the metabolome
Proposal summary: 

Early puberty may lead to the development of several different types of cancer in both men and women. This project aims to find out whether this increased cancer risk is partly due to adverse effects of early puberty on metabolism. To do this, we will examine links between genetic predispositions for timing of puberty and markers of body fat, along with a wide range of detailed blood-based markers of metabolic functioning. Data on ALSPAC mothers and children are particularly useful for seeing how genetic predispositions to early puberty affect fat and lean mass differently, and how these affect metabolic functioning at different stages of sexual maturity. Data on men from a separate cancer-specific study will also be examined to see how development of cancer affects links between puberty timing and metabolism. All results will be compared with those obtained from a separate analysis of genetic predispositions for puberty timing on metabolites using larger-scale collaborative data.

Impact of research: 
The immediate impact of this research will likely be at least 1 peer reviewed publication in a general medical journal (i.e. PLOS Medicine). We aim to present and discuss results in a way that is robust enough for academics but is accessible and relevant to clinicians and public health practitioners, ultimately encouraging greater attention to early life exposures and better prevention of disease.
Date proposal received: 
Friday, 2 December, 2016
Date proposal approved: 
Monday, 5 December, 2016
Keywords: 
Epidemiology, Cancer, Diabetes, Obesity, GWAS, Metabolomics, NMR, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Metabolic - metabolism, Puberty

B2799 - Associations between Adolescent Anxiety and Alcohol Use in Young Adulthood - 2016/05/12

B number: 
B2799
Principal applicant name: 
Maddy Dyer | IEU, School of Experimental Psychology, School of Social and Community Medicine (University of Bristol) (England)
Co-applicants: 
Professor Marcus Munafo, Professor Matthew Hickman
Title of project: 
Associations between Adolescent Anxiety and Alcohol Use in Young Adulthood
Proposal summary: 

Anxiety is associated with alcohol use. However, different hypotheses exist regarding the direction of these associations and evidence is inconsistent. Following on from a recent experimental study which found that state anxiety leads to higher alcohol choice, this epidemiological study will investigate the relationship between adolescent anxiety and alcohol use in young adulthood.

Impact of research: 
Anxiety and alcohol problems are both major public health concerns. It is important to investigate the direction of this relationship and factors which may affect the strength of this relationship. Identifying drinking-to-cope motive as a moderator could potentially inform targeted interventions for young people with anxiety, which in turn may reduce their risk of alcohol problems.
Date proposal received: 
Monday, 28 November, 2016
Date proposal approved: 
Monday, 5 December, 2016
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Mental health, Statistical methods, Mental health, anxiety, alcohol use, alcohol dependence

B2792 - PEARL Assessment of pilot Police National Computer linkage exercise - 2016/01/12

B number: 
B2792
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
John Macleod, Rita Doerner, Matt Hickman, Joeseph Murray, Barbarra Maughan, Rosie Cornish
Title of project: 
PEARL: Assessment of pilot Police National Computer linkage exercise
Proposal summary: 

ALSPAC can collect information on participants life events through linking to their routine administrative records held by UK government. These are the records that all of us build up as we use government services (such as school records or GP records) or interact with government in other ways. For some participants, this will include records of criminal convictions and cautions. As part of ALSPACs work to establish these linkages we have conducted a pilot exercise linking some participants to their Police National Computer (PNC) database records (see project B557 for this work). The result of this linkage was a completely anonymous dataset, i.e. it includes ALSPAC participants PNC records, but cannot be linked to the ALSPAC dataset. In this project we would like to conduct simple comparisons of criminal records in this pilot exercise with participant reported criminality information provided at focus clinic and in questionnaires. The evidence will help inform the development of our linkage strategy.

Impact of research: 
We aim to advance the understanding of how criminal records can be linked to observational cohort studies.
Date proposal received: 
Monday, 21 November, 2016
Date proposal approved: 
Thursday, 1 December, 2016
Keywords: 
Epidemiology, Cohort studies - attrition, bias, participant engagement, ethics, Linkage, Criminality

B2797 - The relationship between flavonoids cognition and depression in children - 2016/01/12

B number: 
B2797
Principal applicant name: 
Amy Jennings | University of East Anglia (United Kingdom)
Co-applicants: 
Professor Aedin Cassidy, Faith Orchard
Title of project: 
The relationship between flavonoids, cognition and depression in children
Proposal summary: 

It is known that diet can have a significant impact on the development and function of the brain and growing evidence suggests links between diet, cognition and mood disorders. Dietary flavonoids are the most common polyphenolic compounds in the diet, they occur naturally in plant foods and are present in substantial amounts in commonly consumed fruits and vegetables. A number of plausible biological mechanisms link intake of flavonoids to both mood disorders such as depression and cognition, including an increase in blood flow to the brain which may lead to nerve cell growth and the formation of new blood vessels and a reduction in neuro-inflammation, an important contributor to depression. In a study of over 80,000 adults, we found that a higher intake of flavonoids from citrus fruits was associated with a 10% lower risk of depression (Chang et al. 2016). Furthermore, flavonoid clinical trials have reported significant benefits to cognition, mainly in the executive function (cognitive control) domain (Macready et al. 2009).

Adolescence is both a period of significant cognitive development and a period of high risk for developing mood disorders; thus it is an ideal time to target preventive interventions. This project will examine a number of commonly consumed flavonoid subclasses in order to assess which flavonoids are most effective for preventing low mood and cognitive dysfunction in children. Different flavonoid sub-classes have shown to differ in both bioactivity and bioavailability and are therefore likely to show differential associations with our outcomes.

Impact of research: 
There is increasing recognition of the importance of dietary risk factors to enhance well-being by improving mood and enhancing cognitive function. Data from the Mental Health of Children and Young People in Great Britain Survey indicates that 12% of young people aged 11–16 years have a clinically diagnosed mental disorder and 5% have an emotional disorder (anxiety or depression). Furthermore, the average age of onset for anxiety and mood disorders is 6 years and 13 years, respectively. It is therefore clear that depression and other mood disorders constitute a major public health problem with a significant personal, social and economic burden and the potential for early intervention using strategies targeted at improving dietary intake at a population level may be of substantial public health benefit. In order to be able to provide recommendations for clinical practice and information and support for dietary improvement to those with mood disorders dietary interventions are required. This work will provide much needed evidence to support the development of human trials that if targeted at young people have the potential to prevent the onset of mood disorders. Understanding more about how specific dietary components may promote health and well-being will also facilitate the development of more specific dietary guidelines for enhancing mood and cognitive function. Flavonoid research has the potential to make significant contribution to the knowledge base needed to refine the current, rather general, fruit and vegetable dietary recommendations.
Date proposal received: 
Monday, 28 November, 2016
Date proposal approved: 
Thursday, 1 December, 2016
Keywords: 
Epidemiology

B2789 - Replication of var meQTLs - 2016/01/12

B number: 
B2789
Principal applicant name: 
Juan E. Castillo-Fernandez | Department of Twin Research, King's College London (UK)
Co-applicants: 
Gibran Hemani
Title of project: 
Replication of var meQTLs
Proposal summary: 

Quantitative trait loci (QTLs) studies have been successful identifying regions of the genome associated with inter-individual differences in DNA methylation. A common approach to explore the impact of genetic variants on DNA methylation is based on assessing differences in the mean methylation levels. However, QTLs may also contribute to the amount of variability of epigenetic marks (var QTLs). We identified var QTLs for DNA methylation in whole-blood using MZ twins-discordance as a measure of variability and are interested in the replication of these var meQTLs in an independent cohort.

Impact of research: 
Replication of our results will be crucial to ensure that the findings are robust. The research has the potential to suggest new mechanism through which genetic variation causes epigenetic variability and ultimately disease.
Date proposal received: 
Thursday, 17 November, 2016
Date proposal approved: 
Thursday, 1 December, 2016
Keywords: 
Genetics, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

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