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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B2934 - An ethical and technical framework for linking social media data in UK cohorts - 17/08/2017

B number: 
B2934
Principal applicant name: 
Oliver Davis | MRC Integrative Epidemiology Unit at the University of Bristol (UK)
Co-applicants: 
Dr Claire Haworth, Dr Andrew Boyd, Dr Lisa Calderwood, Dr Luke Sloan
Title of project: 
An ethical and technical framework for linking social media data in UK cohorts
Proposal summary: 

Information derived from social media platforms such as Twitter and Facebook has the potential to greatly increase our understanding of the origins and consequences of mental health and disorder. However, we need to make sure that when researchers link social media data in cohorts such as Children of the 90s this is done in a secure and ethical way that takes into account the preferences of the participants. We will engage with cohort participants and leaders to work out what is and what is not acceptable in linking social media data, and develop an ethical and technical system for doing this that can be replicated across UK cohort studies.

Impact of research: 
The framework developed by the project could greatly increase the potential for research into the causes and consequences of mental health and disorder in the CLOSER cohorts. Conversely, linking social media to well characterised longitudinal cohorts is likely to revolutionise the potential of other social media studies by bringing together these new measures with traditional measures in the same samples, providing crucial evidence about the circumstances when inferences drawn from online networks are likely to be valid.
Date proposal received: 
Wednesday, 16 August, 2017
Date proposal approved: 
Thursday, 17 August, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Eating disorders - anorexia, bulimia, Mental health, Computer simulations/modelling/algorithms, Qualitative study, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Communication (including non-verbal), Development, Environment - enviromental exposure, pollution, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Psychology - personality, Social science, Speech and language, Statistical methods

B2929 - Exploring polygenic influences on the risk of developmental disorders in the DDD consortium with ALSPAC as controls - 09/08/2017

B number: 
B2929
Principal applicant name: 
Jeffrey Barrett | Wellcome Trust Sanger Institute
Co-applicants: 
Title of project: 
Exploring polygenic influences on the risk of developmental disorders in the DDD consortium, with ALSPAC as controls
Proposal summary: 

The Deciphering Developmental Disorders Study has recruited a large cohort of ~13,000 patients with severe developmental disorders (DDs) and is conducting exome sequencing on them and their parents in order to try to uncover the causal genetic mutations (Wright et al., 2015; Deciphering Developmental Disorders Study, 2017). This is a highly heterogeneous cohort, and the most common phenotypes include intellectual disability (79%), seizures (19%) and autism spectrum disorders ASDs) (12%). We have discovered a damaging mutation in approximately 1/3 of the cohort that is thought to account for all or most of their phenotype.

However, it is becoming increasingly clear that common diseases, and in particular, psychiatric phenotypes, can have both common and rare genetic variants contributing to aetiology (Gaugler et al., 2014; Singh et al., 2016; Pardiñas et al., 2016). Thus, we have been investigating the potential role of common variation in DD, using genome-wide genotype data on ~8,000 DDD probands and ~13,000 ancestry-matched controls. We have shown, using these data, that common variants contribute a small proportion of the variation in risk of DD (heritability=9.3%; standard error=4.0%), and also that there is a significant genetic correlation (rg=-0.77; p=5.1E-6) between DD risk and educational attainment (EA) in the general population (i.e. correlation in the phenotypes due to shared polygenic background). In order to increase our power to perform further common variant analyses, we would like to add the ALSPAC data as additional controls, so we are seeking access to the genotype data as well as data on EA and IQ measures.

References:
Deciphering Developmental Disorders Study. Prevalence and architecture of de novo mutations in developmental disorders. Nature, 542, 433–438 (2017).

Gaugler et al. Most genetic risk for autism resides with common variation. Nat. Genet. 46(8) 881-885 (2014).

Pardiñas et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection. Biorxiv. (2016).

Singh et al. The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nat. Genet. 49(8):1167-1173 (2016).

Wright,C.F., Fitzgerald,T.W., Jones,W.D., Clayton,S., McRae,J.F., van Kogelenberg,M., King,D.A., Ambridge,K., Barrett,D.M., Bayzetinova,T., et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet, 385, 1305–1314 (2015).

Impact of research: 
Our research will lead to a better understanding of the genetic architecture of developmental disorders, demonstrating (if robustly replicated) that common genetic variation plays a role in disorders traditionally viewed as purely monogenic. Our results may have important implications in understanding variable clinical presentation and will be useful in the continued search for both primary genetic diagnoses of developmental disorders and secondary genetic modifiers. Additionally, our results may shed light on how different recruitment strategies can lead to subtle confounding in genetic correlation analyses.
Date proposal received: 
Tuesday, 8 August, 2017
Date proposal approved: 
Wednesday, 9 August, 2017
Keywords: 
Genetics, Learning difficulty, GWAS, Cohort studies - attrition, bias, participant engagement, ethics, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Intelligence - memory

B2930 - GWAS metabolomics NMR - 09/08/2017

B number: 
B2930
Principal applicant name: 
Nicholas Timpson | UoB (UK)
Co-applicants: 
Dr David Hughes
Title of project: 
GWAS metabolomics (NMR)
Proposal summary: 

This project is the third run of a basic project - to map the contribution of common genetic variation to circulating levels of small molecules/metabolites. ALSPAC has not been involved before and this presents an excellent opportunity for the study to use its NMR data to contribute to new genetic research.

Impact of research: 
A major resource for the instrumentation of metabolites in causal analyses.
Date proposal received: 
Wednesday, 9 August, 2017
Date proposal approved: 
Wednesday, 9 August, 2017
Keywords: 
Genetics, Anything downstream of metabolites., GWAS, Metabolic - metabolism

B2920 - BMI gene x activity interactions - 09/08/2017

B number: 
B2920
Principal applicant name: 
Tim Frayling | University of Exeter (UK)
Co-applicants: 
Dr Andrew Wood, Dr Rebecca Richmond, Prof George Davey Smith, Prof Debbie Lawlor
Title of project: 
BMI gene x activity interactions
Proposal summary: 
Impact of research: 
Previous studies of BMI gene x activity have been limited to either very small numbers or self report measures of activity. Using the UKbiobank adults and ALSPAC children (and mothers) to test these interactions, regardless of the result, will represent a major step forward for the “GxE” field.
Date proposal received: 
Wednesday, 26 July, 2017
Date proposal approved: 
Wednesday, 9 August, 2017
Keywords: 
Genetics, Obesity, Statistical methods, Sex differences

B2926 - Using polygenic risk scores in repeated measures analysis for increased statistical power and causal inference - 08/08/2017

B number: 
B2926
Principal applicant name: 
Alex Kwong | Integrative Epidemiology Unit (IEU)
Co-applicants: 
Tim Morris, Professor Kate Tilling, Dr Neil Davies, Dr Laura Howe
Title of project: 
Using polygenic risk scores in repeated measures analysis for increased statistical power and causal inference
Proposal summary: 

Polygenic risk scores (PGS) are being used more frequently with the emergence of new genome wide association study (GWAS) findings, opening new possibilities for understanding how genes associate with health and socioeconomic traits. However, much of the research using PGS may be underpowered, resulting in a failure to identify associations with traits or even spurious associations. Previous work conducted in similar projects has explored differences in the predictive power of a PGS when modelled using various strategies such as a phenotype measured at single or multiple occasions. We wish to extend this work in three ways. Firstly, as a proof of principle, we will compare the predictive power of different PGS using single and repeated measure phenotypes including mood (depression), substance use (cannabis use) and anthropometric measures (blood pressure and height). Secondly, we will extend upon previous Mendelian Randomisation analyses to determine the statistical benefits of modelling an exposure and/or an outcome in a repeat measure framework. Finally, we will investigate the potential for increasing power in GWAS’ by using a repeated measures framework to determine if power can be maximised by using repeated measures rather than increased sample size. To meet these ends, we require phenotypic and genomic data at multiple occasions for mood, substance use and anthropometric measures. ALSPAC is the perfect resource for conducting this research given its impressive archive of data and sample.

Impact of research: 
If all goes to plan, we will be able to have some estimates of causal inference for various diseases.
Date proposal received: 
Friday, 4 August, 2017
Date proposal approved: 
Tuesday, 8 August, 2017
Keywords: 
Genetics, Statistical methods, Blood pressure, Psychology - personality, Statistical methods

B2927 - Socioeconomic differentials in physical activity by age and cohort enhancing the CLOSER cohort resource to inform research - 08/08/2017

B number: 
B2927
Principal applicant name: 
Rachel Cooper | MRC Unit for Lifelong Health and Ageing at UCL (UK)
Co-applicants: 
Dr David Bann, Professor Michaela Benzeval, Dr Lucy Griffiths, Professor Mark Hamer, Dr Snehal Pinto-Pereira, Dr Nic Timpson
Title of project: 
Socioeconomic differentials in physical activity by age and cohort: enhancing the CLOSER cohort resource to inform research
Proposal summary: 

Physical activity (PA) has a critical role to play in addressing two of the most important public health challenges of modern times: the rising prevalence of obesity and population ageing.
Despite the publication of national and international recommendations which aim to promote the uptake and maintenance of PA across life, a significant proportion of the world’s population still do not regularly participate in PA. To address this challenge we need to better understand the determinants of PA. While many determinants of PA have been identified, it is often not possible, due to a lack of suitable data, to assess the impact of age-related changes and secular trends in PA on these associations. This is a significant limitation as the influence of different determinants may vary by age and birth cohort with important implications for the targeting of interventions. Essential insights are thus to be gained from investigating age and cohort differences in associations where comparable data are available; coordinated analyses of data from CLOSER studies provide a unique opportunity to do this across the life course in a UK setting.

Impact of research: 
To foster collaborative links between different UK studies with comparable data on physical activity and to identify strategies to maximise the value of the relevant data available within the CLOSER resource to answer important, policy relevant research questions on physical activity in the future.
Date proposal received: 
Monday, 7 August, 2017
Date proposal approved: 
Tuesday, 8 August, 2017
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Physical - activity, fitness, function

B2928 - Maternal paternal and offspring body size Genome Wide Complex Trait Analysis - 08/08/2017

B number: 
B2928
Principal applicant name: 
Marjo-Riitta Jarvelin | Imperial College London (UK)
Co-applicants: 
Tom Bond, Debbie Lawlor, Alex Lewin, Paul O'Reilly, Sylvain Sebert, Maneka De Silva
Title of project: 
Maternal, paternal and offspring body size: Genome Wide Complex Trait Analysis
Proposal summary: 
Impact of research: 
This work forms part of a PhD project which is aiming to estimate the extent to which the association between maternal BMI during pregnancy and offspring BMI in childhood/adulthood is explained by genetic confounding. We hope to submit several publications to high impact journals, and if we are able to demonstrate a large degree of genetic confounding then this may suggest that maternal BMI during pregnancy is a largely non-modifiable risk factor for offspring obesity, which will have important public health implications.
Date proposal received: 
Monday, 7 August, 2017
Date proposal approved: 
Tuesday, 8 August, 2017
Keywords: 
Epidemiology, Obesity, Genome wide complex trait analysis (GREML), BMI, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Fathers, Mothers - maternal age, menopause, obstetrics, Offspring

B2931 - Antenatal Selection Gradients - 10/08/2017

B number: 
B2931
Principal applicant name: 
Dr Dalton Conley | Princeton University (United States)
Co-applicants: 
Ms Ramina Sotoudeh
Title of project: 
Antenatal Selection Gradients
Proposal summary: 
Impact of research: 
The impact of this research will span many fields. First it will inform our understanding of how genes interact with the prenatal environment, and whether they can make a zygote or an embryo more or less resistant to harsher prenatal environments. Second, it will help us understand the extent to which and under what conditions genes are randomly allocated to offspring according to the parental genomes. This is often assumed to be random and our findings will reveal whether this assumption is warranted. Third, this project could be important to the field of public health, revealing how parental age, stress and behaviors impact the genetic makeup of offspring, and will help inform our understanding of the relationship between larger demographic process in societies (such as increases in the average age of mothers) and the long-term genetic composition of those societies.
Date proposal received: 
Tuesday, 25 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Clinical research/clinical practice, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Offspring

B2914 - Estimating methylation derived neutrophil to lymphocyte ratio mdNLR a measure of systemic inflammation in ARIES samples - 02/08/2017

B number: 
B2914
Principal applicant name: 
Srikant Ambatipudi | MRC-IEU (United Kingdom)
Co-applicants: 
Dr. Paul Yousefi, Dr. Gemma Sharp, Professor Caroline Relton
Title of project: 
Estimating methylation derived neutrophil to lymphocyte ratio (mdNLR): a measure of systemic inflammation in ARIES samples
Proposal summary: 
Impact of research: 
The present study aims to estimate inflammation using the DNA methylation data. In doing so it we would assess if DNA based methylation estimates are associated with inflammatory disorders. The results generated through the study would bridge the knowledge gap in the field of systemic inflammation based disorders.
Date proposal received: 
Thursday, 20 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Epidemiology, Allergy, Epigenetics, Immunity

B2916 - Maternal Mental Health and Child Development - 02/08/2017

B number: 
B2916
Principal applicant name: 
Dawn Kingston (RN, PhD) | University of Calgary (Canada)
Co-applicants: 
Muhammad Kashif Mughal (MBBS, PhD), Anna L. Mackinnon (BA), Rebecca Giallo (PhD), Abdul Wajid (MBBS, PhD), Katherine Bright (RN, MN), Paula Harvalik (RN, MN), Mireille Lecharrois (RN, MN), Karly Jarema (BScN), Lydia Vermeyden BSc, Msc
Title of project: 
Maternal Mental Health and Child Development
Proposal summary: 
Impact of research: 
This research will help us better understand the chronicity and severity of maternal mental health over time allowing us to identify women experiencing a broader spectrum of mental health symptoms. In addition this research will inform how the trajectories of maternal mental health over time impact child development, physical and mental health across childhood and adolescence. This research will contribute novel findings about mechanisms that will inform screening and intervention strategies. This has the potential to improve maternal mental health and mitigate the risks of associated child outcomes.
Date proposal received: 
Thursday, 20 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, BMI, Development, Maternal mental health, child mental health, child development, child physical health

B2917 - Genetic influences on behavioral and psychopathological outcomes - 02/08/2017

B number: 
B2917
Principal applicant name: 
Jonathan Hess | SUNY Upstate Medical University (USA)
Co-applicants: 
Dr. Stephen Faraone, Dr. Seetha Ramanathan, Cheryl Roe, Nick Nguyen
Title of project: 
Genetic influences on behavioral and psychopathological outcomes.
Proposal summary: 
Impact of research: 
Our project addresses a fundamental question regarding the validity of RDoC constructs and our currently psychiatric nosology. Currently our lab is seeking to validate and assess Positive Valence System constructs of RDoC, which reflect reward system processing in the brain, using multi-layered and multi-variable approach to find genetic, behavioral, and neurobiological factors associated with these constructs. We will follow a similar approach with existing data generated by ALSPAC, but will consider RDoC constructs that have not yet been validated by our work or others. Our project may uncover fundamental relationships between the expression of psychiatric disorders and objective "units of analysis" (i.e., genes, molecules, circuits, behaviors, and questionnaires/inventories), and provide a framework for predicting mental disorders.
Date proposal received: 
Monday, 24 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2918 - MR-pheWAS of favourable adiposity - 02/08/2017

B number: 
B2918
Principal applicant name: 
Louise AC Millard | IEU, UoB
Co-applicants: 
Professor Tim Frayling, Dr Hanieh Yaghootkar
Title of project: 
MR-pheWAS of "favourable" adiposity
Proposal summary: 
Impact of research: 
This work will show whether associations identified in adults also exist in children, and may identify potentially novel associations with other traits and disease.
Date proposal received: 
Tuesday, 25 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Epidemiology, Diabetes, Hypertension, heart disease, MR-pheWAS, Blood pressure, BMI

B2919 - Quantifying potential publication bias in observational studies using a natural registry A feasibility study - 02/08/2017

B number: 
B2919
Principal applicant name: 
Kate Northstone | ALSPAC
Co-applicants: 
Dr Jelena Savovic, Professor Jonathan Sterne, Professor Marcus Munafo
Title of project: 
Quantifying potential publication bias in observational studies using a natural registry: A feasibility study
Proposal summary: 
Impact of research: 
This is a pilot study to develop the methodology and feasibility in order to inform a larger proposal to go to the MRC methodology panel. The results will make a significant contribution to the over field of evidence based medicine (and other disciplines) by enabling us to quantify the extent of publicaiton bias for observational studies which has never been done before.
Date proposal received: 
Tuesday, 25 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Epidemiology, Cohort studies - attrition, bias, participant engagement, ethics

B2922 - The interplay between perinatal mood and infant sex in the development of child and adolescent mental health difficulties - 02/08/2017

B number: 
B2922
Principal applicant name: 
Jonathan Hill | University of Reading (UK)
Co-applicants: 
Dr Elizabeth Braithwaite, Professor Andrew Pickles, Dr Helen Sharp
Title of project: 
The interplay between perinatal mood and infant sex in the development of child and adolescent mental health difficulties
Proposal summary: 

Exposure to maternal depression and anxiety during pregnancy and the postnatal period increases the risk of behavioral, emotional and cognitive difficulties in childhood, and also increases risk of mental health disorders, such as depression and anxiety, in adolescence. However, due to the complex nature of genetic and environmental contributions to the onset of mental health disorders, the process by which perinatal depression increases risk for offspring psychopathology remains unclear.

Recent research from our group and others suggests that the interplay between prenatal and postnatal depression may be important when considering childhood outcomes, and also that there may be specific gender differences in the development of childhood and adolescent mental health difficulties.

This project will use data from a large sample of children born in the early 1990s and their families. Measures of maternal depression were taken regularly during pregnancy and after birth, as were measures of childhood behavior, emotionality and cognitive function. Further, mental health was assessed at a number of time points during adolescence, when depression and anxiety are at peak onset. This information will allow us to question whether combinations of prenatal and postnatal depression are important in predicting offspring mental health, and whether such associations may be different for male and female infants. If this project does identify sex-specific associations between perinatal depression and offspring mental health, this may lead to targeted gender-specific interventions to avert the onset of mental health difficulties.

Impact of research: 
This research will further our scientific understanding of the way maternal prenatal and postnatal depression operate in the prediction of childhood and adolescent mental health outcomes, and whether there are important sex differences. There are a number of implications of this research. Firstly, the results of this study may allow us to identify which infants may be most at risk of developing later difficulties following exposure to perinatal depression, which has clinical implications for current intervention strategies. Secondly, our findings will further our understanding of the pathways by which exposure to maternal depression during the perinatal period may lead to mental health difficulties in later life, which will have positive implications for the design and implementation of new and targeted intervention and prevention strategies. This project has been proposed following our recent findings using data from the Wirral Child Health and Development Study (WCHADS). If we replicate our findings from the WCHADS cohort using the ALSPAC cohort, this will provide further impetus and evidence to study sex-specific biological, behavioral and epigenetic mechanisms that may underpin associations between perinatal depression and offspring mental health outcomes.
Date proposal received: 
Thursday, 27 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Mothers - maternal age, menopause, obstetrics, Offspring, Sex differences

B2923 - Cortisol dysregulation as a mediator between early stress and cardiometabolic risk - 02/08/2017

B number: 
B2923
Principal applicant name: 
Jenalee Doom | University of Michigan (US)
Co-applicants: 
Title of project: 
Cortisol dysregulation as a mediator between early stress and cardiometabolic risk
Proposal summary: 
Impact of research: 
The results of this research will be an understanding of whether cortisol dysregulation during childhood or adolescence is a point of intervention for those who experienced early stress to lower CVD risk. If cortisol dysregulation does mediate these pathways, interventions should incorporate cortisol measures into pre- and post-assessments and potentially aim to restore adaptive cortisol regulation to improve health.
Date proposal received: 
Monday, 31 July, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Social Science, Diabetes, Hypertension, Obesity, Statistical methods, Accelerometry, dietary recall, and serum markers of inflammation and metabolism (existing data within ALSPAC--no new assays), Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Nutrition - breast feeding, diet, Physical - activity, fitness, function, Social science, Blood pressure, BMI, Cardiovascular, Childhood - childcare, childhood adversity, Development, Endocrine - endocrine disrupters, Hormones - cortisol, IGF, thyroid, Metabolic - metabolism

B2925 - Comparing health and health-related outcomes in adolescence between two generations in England ALSPAC and MCS - 02/08/2017

B number: 
B2925
Principal applicant name: 
Suzi Gage | University of Liverpool (and honorary staff at University of Bristol) (UK)
Co-applicants: 
Dr Praveetha Patalay
Title of project: 
Comparing health and health-related outcomes in adolescence between two generations in England (ALSPAC and MCS)
Proposal summary: 
Impact of research: 
This research is likely to be of high interest to researchers, policy makers and the public more generally. We are also keen to use it as a starting point to apply for a grant to investigate the mechanisms for any patterns we might find in this initial analysis. The findings will have impact in various fields including healthcare policy and planning, population health trends, adolescent health.
Date proposal received: 
Wednesday, 2 August, 2017
Date proposal approved: 
Wednesday, 2 August, 2017
Keywords: 
Epidemiology, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B2913 - Metabolic syndrome and asthma in children and adolescents - 26/07/2017

B number: 
B2913
Principal applicant name: 
John Henderson | SSCM
Co-applicants: 
Prof Fernando Martinez, Dr Raquel Granell
Title of project: 
Metabolic syndrome and asthma in children and adolescents
Proposal summary: 
Impact of research: 
High impact publication. Prof Martinez likely to lead this & NEJM/Lancet Respiratory Medicine would be reasonable expectations.
Date proposal received: 
Friday, 14 July, 2017
Date proposal approved: 
Wednesday, 26 July, 2017
Keywords: 
Developmental biology, Respiratory - asthma, Computer simulations/modelling/algorithms, Metabolic - metabolism

B2906 - Season of Birth and methylation profiles in children PACE - 28/06/2017

B number: 
B2906
Principal applicant name: 
Esther Walton | University of Bristol
Co-applicants: 
Dr Gemma Sharp
Title of project: 
Season of Birth and methylation profiles in children (PACE)
Proposal summary: 

Season of birth has previously been associated with allergic disease risk and children born during autumn or winter are more likely to develop asthma, rhinitis, hayfever, and eczema. However, the mechanism by which season of birth is related to disease remains unclear. The epigenome is one method by which environmental factors may alter gene expression that persists over time, leading to an influence upon allergic disease outcome. This analysis will be carried out within the PACE consortium.

Impact of research: 
Findings could lend novel insights into a potential link between DNA methylation and season of birth.
Date proposal received: 
Friday, 23 June, 2017
Date proposal approved: 
Wednesday, 28 June, 2017
Keywords: 
Epidemiology, season of birth, Epigenetics, Biological samples -e.g. blood, cell lines, saliva, etc., Birth outcomes, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Environment - enviromental exposure, pollution, season of birth

B2907 - Physical activity and multi-morbid long-term conditions at age 1113 and 15 27-03-2017 - 141736 - 28/06/2017

B number: 
B2907
Principal applicant name: 
Russell Jago | University of Bristol (UK)
Co-applicants: 
Dr Matt Ridd, Prof John Henderson, Prof Andy Ness, Dr Emma Solomon-Moore, Dr Ruth Salway, Dr Corrie McDonald-Wallis
Title of project: 
Physical activity and multi-morbid long-term conditions at age 11,13 and 15 (27-03-2017 - 14:17:36)
Proposal summary: 
Impact of research: 
These analyses are designed to help build the evidence base for a new line of research that attempts to increase physical activity in children with multiple chronic conditions. Our hypothesis is that this group will be in need of a specific intervention due to lower levels of physical activity. However, the current evidence on this topic is very weak. There are multiple reviews but the quality of the studies is weak and the findings inconsistent.
Date proposal received: 
Wednesday, 28 June, 2017
Date proposal approved: 
Wednesday, 28 June, 2017
Keywords: 
Epidemiology, Eczema, Obesity, Respiratory - asthma, Statistical methods, Physical - activity, fitness, function

B2903 - Genomic epigenetic and environmental risk factors for speech development and learning disability - 28/06/2017

B number: 
B2903
Principal applicant name: 
Catherine Stein | Department of Population and Quantitative Health Sciences (United States)
Co-applicants: 
Dr. Sudha Iyengar, Dr. Robert Igo, Jr., Dr. Barbara Lewis
Title of project: 
Genomic, epigenetic, and environmental risk factors for speech development and learning disability
Proposal summary: 
Impact of research: 
We intend to use these analyses both to replicate our existing findings from a cohort of children in Cleveland, OH, USA, as well as to generate preliminary data for new proposals to examine other questions in this same cohort of children in the USA. Ours will be the first study identifying an association between DNA methylation and phonological memory measures. Our future proposal will focus on disentangling the relationship between LD and communication disorders and how this comorbidity may be caused by genetic, epigenetic, and environmental factors, perhaps in combination. Understanding the influence of these various factors will enable practitioners and parents to better identify risk factors and seek targeted treatment for these disorders.
Date proposal received: 
Monday, 26 June, 2017
Date proposal approved: 
Monday, 26 June, 2017
Keywords: 
Genetics, Learning difficulty, Speech/language problem, DNA sequencing, Epigenetics, Gene mapping, GWAS, Proteomics, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Cognition - cognitive function, Communication (including non-verbal), Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Intelligence - memory, Mothers - maternal age, menopause, obstetrics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Speech and language

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