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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B2969 - The genetics of fear learning and extinction - 18/10/2017

B number: 
B2969
Principal applicant name: 
Thalia Eley | Institute of Psychiatry, Psychology & Neuroscience (UK)
Co-applicants: 
Dr Gerome Breen, Kirstin Purves
Title of project: 
The genetics of fear learning and extinction
Proposal summary: 

Anxiety is a common, costly and growing problem in our society. Despite considerable heritability and being a primary cause of lifelong disability, little is known about the molecular basis of anxiety. However, experimental psychology has developed exceptionally robust paradigms that model in both animals and humans how anxiety (fear) is developed (or learned) and how it is treated (or extinguished). No study has attempted to apply to combine modern genetic approaches with the use of these experimental paradigms at scale, with sufficient power to allow transformative science. We propose to conduct the largest systematic genetic study of an experimental psychology paradigm - fear learning and extinction - in order to significantly advance our understanding of mechanisms underlying the development and treatment of anxiety.We will also develop genetic tools for use in predicting treatment outcome, paving the way for personalised treatment decisions for anxiety disorders.

Impact of research: 
Large and widespread. 1. We expect to write high profile papers from this work as it is at the intersection of cutting edge research across two rarely combined disciplines (experimental psychology and genomics). 2. We expect our work to be of significant interest to clinicians interested in predicting response to psychological treatments, given that extinction is the process that forms the active ingredient of expose-based treatments for anxiety. 3.
Date proposal received: 
Friday, 6 October, 2017
Date proposal approved: 
Tuesday, 10 October, 2017
Keywords: 
Genetics, Mental health, GWAS, Biological samples -e.g. blood, cell lines, saliva, etc.

B2967 - Educational outcomes for children with combined visual and hearing loss - 11/10/2017

B number: 
B2967
Principal applicant name: 
Matilda Hill | University of Bristol
Co-applicants: 
Professor Alan Emond, Cathy Williams, Amanda Hall
Title of project: 
Educational outcomes for children with combined visual and hearing loss
Proposal summary: 

This project will investigate the impact of combined mild hearing and visual loss in childhood on educational attainment in later years.

Background
Problems with vision and hearing are extremely common in childhood. In most cases, the impairment is mild and often transient; severe visual or hearing impairments are relatively rare in the UK.
It is well established that severe visual and hearing impairments have a detrimental effect on childhood development, behaviour and educational attainment. The impact of mild visual or hearing impairment is less well characterized, but appears to be more variable, dependent on additional factors such as underlying cause, duration and socioeconomic factors.
The research question is: what is the effect of combined mild hearing and visual impairment on development during childhood and educational attainment?.

Project Description
Using data from the ALSPAC study, this project aims to address this question, focusing specifically on the educational attainment of children with combined mild visual and hearing impairments. The ALSPAC birth cohort study has gathered data on over 14,000 individuals, providing us with a unique opportunity to investigate this question.

We will use data collected from the ALSPAC research clinic when participants were 7 years of age to identify all children with both mild visual and hearing impairments.Their subsequent Keystage 2 and GCSE results will be compared with those of children with normal vision and hearing at age 7, and those with a single hearing or visual impairment.

When comparing these results, we will take into account factors that may be independently associated with both hearing and vision in childhood and educational performance. For example, low socioeconomic status is risk factor for problems with vision and hearing, and also associated with lower educational attainment. Other factors we will be adjusting for include gender, birth weight, maternal education and ethnicity.

If our initial results do indicate that combined mild visual and hearing impairments have a negative impact on educational attainment, we will attempt to understand why this is. We will thus look at factors such as working memory, reading skills and co-occuring developmental disorders (Dyslexia, Autism & Dyspraxia) to see if children with combined hearing and visual impairments are more likely to perform worse on these measures, or display particular behavioral traits which may explain differences in educational attainment at age 16.

Finally, the results of this study may have implications for the way children with combined mild visual and hearing impairments are identified and supported through their education.

Impact of research: 
This project will be the first study to investigate the impact of combined minor visual and hearing impairments in childhood on educational attainment In the UK Given the high prevalence of visual and hearing problems in childhood, the results of this project will be of great interest. The results of this research may have significant implications for how children with combined mild visual and hearing impairments should be identified, and whether they should receive additional educational support, and if so, in what area. Currently, most such children will not be receiving formal educational support. Should our research show that these children are likely to attain poorer GCSE grades than their peers, with subsequent implications for further education and employment, this will provide compelling evidence that provision of educational support may be required.
Date proposal received: 
Tuesday, 3 October, 2017
Date proposal approved: 
Thursday, 5 October, 2017
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Learning difficulty, Speech/language problem, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics, Childhood - childcare, childhood adversity, Vision, Cognition - cognitive function, Communication (including non-verbal), Development, ENT - hearing, Environment - enviromental exposure, pollution, Intelligence - memory, Speech and language, Statistical methods

B2965 - Evaluating the causal effect of gene expression on cardiovascular function - 04/10/2017

B number: 
B2965
Principal applicant name: 
Tom Richardson | MRC IEU
Co-applicants: 
Kurt Taylor, Dr Tom Gaunt
Title of project: 
Evaluating the causal effect of gene expression on cardiovascular function
Proposal summary: 

Genome-wide association studies (GWAS) have uncovered hundreds of genetic variants across the human genome which influence cardiovascular disease risk. However, the underlying mechanisms which may explain these effects have yet to be explored in detail. This project aims to develop our understanding of these mechanisms by assessing changes in gene expression levels.

Impact of research: 
As mentioned above we hoped to identify genetic variants which influence cardiovascular disease risk by changes in gene expression.
Date proposal received: 
Thursday, 28 September, 2017
Date proposal approved: 
Wednesday, 4 October, 2017
Keywords: 
Genetics, Obesity, Gene expression, BMI

B2966 - Patterns prevalence and disease trajectories of food allergy in adults - 11/10/2017

B number: 
B2966
Principal applicant name: 
John Henderson | ALSPAC
Co-applicants: 
Professor Graham Roberts, Clare Mills
Title of project: 
Patterns, prevalence and disease trajectories of food allergy in adults
Proposal summary: 

The project aims to use a combination of existing and new epidemiological data and data from adults attending allergy clinics in the UK to determine the prevalence of food allergy in adults, to describe the phenotypes of food allergy (adult-onset, persisting childhood-onset, threshold dose of allergen, type of food allergens) adn to describe the different trajectories of the development and natural history of food allergy across the lifecourse.

Impact of research: 
Impact on policy of Food Standards Agency
Date proposal received: 
Wednesday, 4 October, 2017
Date proposal approved: 
Wednesday, 4 October, 2017
Keywords: 
Immunology, Allergy, Statistical methods, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.

B2964 - UNICORN Unified Cohorts Research Network Disaggregating asthma and allergic diseases - 04/10/2017

B number: 
B2964
Principal applicant name: 
Adnan Custovic | Imperial College London
Co-applicants: 
John Henderson, Andy Boyd, John Macleod
Title of project: 
UNICORN (Unified Cohorts Research Network): Disaggregating asthma and allergic diseases
Proposal summary: 

Asthma and allergic diseases (food allergies, rhinitis, eczema) are the most common chronic diseases in childhood and adolescence. They usually start before school-age and are responsible for a heavy burden of ill health, including premature death. In response, we propose an innovative scientific research program which embraces a truly trans-disciplinary team science approach, and is of fundamental relevance both to biomedical research and to evidence-based health science more broadly. UNICORN builds directly on the substantive prior investments in both the science and infrastructure underpinning research in this domain. The project will assist UK to leverage its cohort studies with a focus on asthma and allergy more productively, and to develop a sustainable, scalable scientific infrastructure to facilitate future work in this and other biomedical domains.

Impact of research: 
The results of the proposed project may lead to the development of methods for prevention that are endotype-specific and to identification of endotype-specific novel therapeutic targets (through better understanding of genetic associates and disease mechanisms). The findings may represent potentially valuable intellectual property, which we will seek to commercialise in collaboration with companies with interests in diagnostics and/or therapeutics. Participating universities have mechanisms and structures in place for exploring industrial applications both during and at the end of the lifecycle of the programme.
Date proposal received: 
Wednesday, 27 September, 2017
Date proposal approved: 
Thursday, 28 September, 2017
Keywords: 
Epidemiology, Respiratory - asthma, Linkage

B2963 - The strucuture of the placental chorionic plate vessels and its relationship to childhood retinal microvascular structure - 02/10/2017

B number: 
B2963
Principal applicant name: 
Vicki Clifton | Mater Research Institute-University of Queensland (Australia)
Co-applicants: 
Prof Susan Ring
Title of project: 
The strucuture of the placental chorionic plate vessels and its relationship to childhood retinal microvascular structure
Proposal summary: 

Placental size and dimensions are linked to later disease susceptibility especially cardiovascular disease. We have recently identified that an in utero insult is associated with altered vascular structure in the eye. We want to determine if there is a link between the placental vascular development and the development of the vascular system in the eye. It may be possible to predict cardiovascular risk in later life by examining the vascular structure of the placenta

Impact of research: 
Will contribute to the growing body of knowledge associated with the developmental origins of cardiovascular disease
Date proposal received: 
Wednesday, 27 September, 2017
Date proposal approved: 
Wednesday, 27 September, 2017
Keywords: 
Developmental biology, Hypertension, Computer simulations/modelling/algorithms, Cardiovascular

B2960 - Social environmental and epigenetic predictors of atopic dermatitis disease course - 04/10/2017

B number: 
B2960
Principal applicant name: 
Katrina Abuabara, MD, MA, MSCE | University of California San Francisco (UCSF) (United States)
Co-applicants: 
Sinead Langan, Chuck McCulloch, PhD, Lindsey Criswell, MD
Title of project: 
Social, environmental, and epigenetic predictors of atopic dermatitis disease course
Proposal summary: 

Atopic dermatitis (AD, also known as ‘atopic eczema’ or simply ‘eczema’) is one of the most common chronic dermatologic diseases and is characterized by intense pruritus, sleep disturbances, and large reductions in patients’ quality of life. It may increase the risk of allergies and asthma, and has recently been characterized as a systemic inflammatory disorder. Clinical treatment guidelines recommend standardized approaches for most patients, but emerging evidence and the highly variable clinical course suggest that personalized interventions hold the promise of much more efficacious treatment. Identifying groups of individuals with similar patterns of disease activity will facilitate the identification of factors that drive disease activity over time and form the basis for studies that seek to identify more tailored interventions.

AD has become much more common over the past few decades, suggesting that environmental factors play an important role in the disease. Many studies have found relationships between early life exposures and AD onset, but few have examined how environmental factors affect disease activity over time. Epigenetic factors (functionally relevant changes in chromosomes that do not affect the DNA sequence including methylation patterns) are hypothesized to link socio-environmental exposures with disease trajectory.

The objectives of our study are three fold: (1) to identify subgroups of individuals with distinct disease trajectories (for example, early-onset resolving, early-onset persistent, and late-onset), (2) to determine the extent to which in utero and early life nutritional, microbial, toxic and stress-related exposures are associated with disease trajectory, and (3) to test the extent to which the associations between in utero and early life risk factors are explained by methylation changes that affect how DNA is transcribed.

Impact of research: 
The likely impact of this work includes better prognostic information regarding AD disease trajectory, data to inform future studies of whether new treatments are disease-modifying, data to develop biomarkers to better stratify patients, and advancements in our understanding of how social and environmental factors affect the biology of disease. Most epidemiologic studies of AD have focused on childhood disease because it presents early in life, and school children are an accessible population for research.[15] As a consequence, very little is known about AD after early childhood. The few population-based studies of adults with AD suggest that the prevalence may be similar to childhood disease, but they are cross-sectional and rely on patient self-report.[16-18] Our proposed research will help to fill an important gap around the trajectory of AD in the late childhood and teenage years, and will provide meaningful prognostic information for clinicians, patients and their families, whose first question when diagnosed with AD is often “when will we get better?” Additionally, addressing the gaps in our knowledge of AD disease trajectory is important for clinical care because it may help to identify patients who are candidates for earlier or more aggressive systemic treatment. It is especially pertinent when weighing the risks and benefits of treating children with new (and costly) biologic, dozens of which are currently in the research and clinical testing pipeline.[19] Our work will also help to identify which patients may benefit from avoidance of specific environmental triggers (which has been identified as a research priority by UK patients).[20] Finally, the characterization of disease trajectory as proposed herein, is an essential step towards the development of disease-modifying strategies. Most clinical trials of new systemic agents for AD enroll adult patients with a history of disease for 2+ years, but don’t differentiate between those with different patterns of disease, which may be important for identifying heterogeneity in treatment response. References 1. Abuabara, K., et al., Development and Validation of an Algorithm to Accurately Identify Atopic Eczema Patients in Primary Care Electronic Health Records from the UK. J Invest Dermatol, 2017. 2. Skrondal, A. and S. Rabe-Hesketh, Generalized latent variable modeling : multilevel, longitudinal, and structural equation models. Chapman & Hall/CRC interdisciplinary statistics series. 2004, Boca Raton: Chapman & Hall/CRC. xi, 508 p. 3. Collins, L.M. and S.T. Lanza, Latent class and latent transition analysis : with applications in the social behavioral, and health sciences. Wiley series in probability and statistics. 2010, Hoboken, N.J.: Wiley. xxxiii, 285 p. 4. Nylund, K.L., T. Asparoutiov, and B.O. Muthen, Deciding on the number of classes in latent class analysis and growth mixture modeling: A Monte Carlo simulation study. Structural Equation Modeling-a Multidisciplinary Journal, 2007. 14(4): p. 535-569. 5. Flohr, C. and L. Yeo, Atopic dermatitis and the hygiene hypothesis revisited. Curr Probl Dermatol, 2011. 41: p. 1-34. 6. Sherriff, A., J. Golding, and T. Alspac Study, Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool infants. Arch Dis Child, 2002. 87(1): p. 26-9. 7. McDade, T.W., et al., Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood. Proc Natl Acad Sci U S A, 2017. 114(29): p. 7611-7616. 8. Paternoster, L., et al., Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet, 2015. 47(12): p. 1449-56. 9. Houseman, E.A., et al., DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics, 2012. 13: p. 86. 10. Wei, J.H., et al., A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma. Nat Commun, 2015. 6: p. 8699. 11. Orozco, L.D., et al., Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice. Cell Metab, 2015. 21(6): p. 905-17. 12. Benton, M.C., et al., Methylome-wide association study of whole blood DNA in the Norfolk Island isolate identifies robust loci associated with age. Aging (Albany NY), 2017. 9(3): p. 753-768. 13. Rakyan, V.K., et al., Epigenome-wide association studies for common human diseases. Nat Rev Genet, 2011. 12(8): p. 529-41. 14. Huynh, J.L., et al., Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci, 2014. 17(1): p. 121-30. 15. Williams, H.C., Epidemiology of human atopic dermatitis--seven areas of notable progress and seven areas of notable ignorance. Vet Dermatol, 2013. 24(1): p. 3-9 e1-2. 16. Montnemery, P., et al., Prevalence of self-reported eczema in relation to living environment, socio-economic status and respiratory symptoms assessed in a questionnaire study. BMC Dermatol, 2003. 3: p. 4. 17. Wolkewitz, M., et al., Lifetime prevalence of self-reported atopic diseases in a population-based sample of elderly subjects: results of the ESTHER study. Br J Dermatol, 2007. 156(4): p. 693-7. 18. Hanifin, J.M. and M.L. Reed, A population-based survey of eczema prevalence in the United States. Dermatitis, 2007. 18(2): p. 82-91. 19. Paller, A.S., K. Kabashima, and T. Bieber, Therapeutic pipeline for atopic dermatitis: End of the drought? J Allergy Clin Immunol, 2017. 140(3): p. 633-643. 20. Batchelor, J.M., et al., The Eczema Priority Setting Partnership: a collaboration between patients, carers, clinicians and researchers to identify and prioritize important research questions for the treatment of eczema. Br J Dermatol, 2013. 168(3): p. 577-82. 21. Hanifin JM, R.G., Diagnostic features of atopic dermatitis. Acta Derm Venereol, 1980. 92 (suppl): p. 44-47. 22. Odhiambo, J.A., et al., Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol, 2009. 124(6): p. 1251-8 e23. 23. Langan, S.M., et al., Increased risk of cutaneous and systemic infections in atopic dermatitis - A cohort study. J Invest Dermatol, 2017. 24. Abuabara, K., et al., Prevalence of physician-diagnosis of atopic eczema across the lifespan: A UK population-based cohort study Under review
Date proposal received: 
Monday, 25 September, 2017
Date proposal approved: 
Monday, 25 September, 2017
Keywords: 
Epidemiology, Epigenetics, Statistical methods, Dermatology, Environment - enviromental exposure, pollution

B2961 - Investigating the impact of cigarette smoking behaviours and time since initiation on DNA methylation patterns in adolescence - 05/10/2017

B number: 
B2961
Principal applicant name: 
Rebecca Richmond | MRC IEU (UK)
Co-applicants: 
Prof Caroline Relton, Miss Claire Prince, Dr Amy Taylor, Dr Nicholas Timpson, Prof Marcus Munafo
Title of project: 
Investigating the impact of cigarette smoking behaviours and time since initiation on DNA methylation patterns in adolescence
Proposal summary: 

Exposure to tobacco smoke has been shown to have a profound effect on DNA methylation patterns in many recent studies. Site-specific DNA methylation in response to smoking is dynamic and may change over time. Although studies have investigated the extent to which changes in DNA methylation that are associated with smoking, persist after smoking cessation (1-3), the length of time required for smoking to have an impact on DNA methylation is currently unstudied. A number of studies, focused on young people and adolescents, have shown that site-specific DNA methylation is associated with smoking (4-9), suggesting that methylation changes may be induced in individuals with a relatively short smoking history. However, the previous studies have typically evaluated methylation at a few CpG sites and have not modelled methylation changes with time since smoking initiation. This study aims to assess the dynamics of smoking-induced genome-wide methylation changes with time since smoking initiation in a cohort of adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Impact of research: 
The results from this research will be of direct relevance to the health of adolescents. This research will give understanding of early epigenetic modification caused by smoking which therefore might inform the early risks of smoking, in adolescents specifically.
Date proposal received: 
Monday, 25 September, 2017
Date proposal approved: 
Monday, 25 September, 2017
Keywords: 
Epigenetics, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Epigenetics, Statistical methods, Environment - enviromental exposure, pollution, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Statistical methods

B2958 - Shift work and health Measuring health outcomes of shift work in longitudinal studies - 25/09/2017

B number: 
B2958
Principal applicant name: 
Wahyu Wulaningsih | MRC Unit for Lifelong Health and Ageing at UCL
Co-applicants: 
Professor Rebecca Hardy, Dr Snehal Pinto Pereira
Title of project: 
Shift work and health: Measuring health outcomes of shift work in longitudinal studies
Proposal summary: 
Impact of research: 
Date proposal received: 
Wednesday, 20 September, 2017
Date proposal approved: 
Monday, 25 September, 2017
Keywords: 
Epidemiology, Mental health, Circadian rhythm disorder Shift work , Statistical methods, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Linkage, Sleep

B2959 - Replication of a novel genetic variant associated with dental development - 25/09/2017

B number: 
B2959
Principal applicant name: 
Simon Haworth | MRC Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Title of project: 
Replication of a novel genetic variant associated with dental development
Proposal summary: 

Dental development begins between the sixth and eighth week of pregnancy. Teeth start to form inside the jaws long before moving to become visible inside the mouth in a process called eruption. The teeth of some children erupt earlier or later than others, and it appears that genetics play a part in regulating this process. The number of teeth in the mouth at age 15 months provides a simple measure of how far children have advanced in their dental development compared to other children the same age, and this data was used some years ago in ALSPAC to identify genetic variants which influence dental development. A collaborating research centre in the Netherlands has identified a genetic variant which they believe alters tooth eruption. Before publishing this finding they have asked us to check whether this variant has a similar effect on tooth eruption in ALSPAC, and cannot do this using the existing published results from ALSPAC as this particular genetic variant was not included in the previous study. We plan to test for association between this genetic variant and number of teeth at 15 months in ALSPAC.

Impact of research: 
This replication analysis will be of benefit in three main ways: a) by helping to build collaboration with the generation R study group b) by providing publicity for ALSPAC and c) by reducing the risk of a false positive association being reported in the literature
Date proposal received: 
Friday, 22 September, 2017
Date proposal approved: 
Monday, 25 September, 2017
Keywords: 
Dentistry, Dental development, Gene mapping, Development, Dental, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc.

B2953 - Economic consequences of depression and obesity evidence from causal inference methods and longitudinal intergenerational data - 20/09/2017

B number: 
B2953
Principal applicant name: 
Laura Howe | MRC IEU (United Kingdom)
Co-applicants: 
Neil Davies, Alisha Davies, Frances Rice
Title of project: 
Economic consequences of depression and obesity: evidence from causal inference methods and longitudinal, intergenerational data
Proposal summary: 

This project investigates whether depression and BMI affect educational attainment and economic activity (e.g. income, occupation), with the goal of providing an economic justification for public health interventions. We will look at whether associations change across the life course and across successive generations, and we will test whether parental depression and BMI affect a child's educational attainment and economic activity.

Impact of research: 
Information about the potential economic benefits of interventions that alter depression or BMI
Date proposal received: 
Wednesday, 13 September, 2017
Date proposal approved: 
Wednesday, 20 September, 2017
Keywords: 
Epidemiology, Mental health, Obesity, Computer simulations/modelling/algorithms, Statistical methods, BMI, Childhood - childcare, childhood adversity, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Social science

B2955 - Lifecourse approach to study of onset development and cessation of cigarette smoking during adolescence and young adulthood - 20/09/2017

B number: 
B2955
Principal applicant name: 
Marie-Pierre Sylvestre | University of Montreal Hospital Research Centre and University of Montreal School of Public Health (Canada)
Co-applicants: 
Jennifer O'Loughlin
Title of project: 
Lifecourse approach to study of onset, development, and cessation of cigarette smoking during adolescence and young adulthood
Proposal summary: 

Lifestyle factors including cigarette smoking, obesity, and alcohol consumption are responsible for 40-60% of cancers in Western countries. We want to better understand the effect of these factors – as well as of mental health problems such as depression, stress, and anxiety – on smoking behaviors in adolescents and young adults. In particular, we are interested in how these factors influence the onset, development, and cessation of cigarette smoking. We will identify the causal associations between initiation of alcohol and cannabis use on these smoking outcomes. By gaining better understanding of why adolescents and young adults begin, continue, and stop smoking cigarettes, we can inform the development of more effective preventive interventions, and ultimately reduce the incidence of cancer later in life.

Impact of research: 
o Adolescence may be a critical period for primary prevention and intervention since it is a time during which risk behaviours are often initiated and consolidate. The present proposal will increase understanding of the contextual determinants of the onset, development, and cessation of cigarette smoking in adolescence and their likelihood of tracking in adulthood. Our work will inform the design of more effective interventions with maximised impact.
Date proposal received: 
Monday, 18 September, 2017
Date proposal approved: 
Wednesday, 20 September, 2017
Keywords: 
Epidemiology, Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Cancer, Mental health, Obesity, Statistical methods, BMI, Development, Physical - activity, fitness, function, Statistical methods

B2954 - Prenatal smoking pre-pregnancy BMI and dental caries experience in the offspring ALSPAC Study - 20/09/2017

B number: 
B2954
Principal applicant name: 
Aderonke Akinkugbe | Virginia Commonwealth University (United States)
Co-applicants: 
Tegwyn Brickhouse
Title of project: 
Prenatal smoking, pre-pregnancy BMI and dental caries experience in the offspring: ALSPAC Study
Proposal summary: 

The prenatal period is a sensitive time for fetal growth and development. Maternal life-style related factors during this critical period affects the health and wellbeing of the developing fetus. Specifically, prenatal exposure to tobacco smoke via maternal smoking during pregnancy, increases the risk for respiratory illnesses [1, 2], asthma [3], cleft lip and palate [4] as well as inflammatory polyarthropathies [5] and childhood obesity [6]. Similar to maternal smoking during pregnancy, maternal overweight and obesity is associated with adverse birth outcomes and has been reported in at least one study to exceed smoking as a risk factor with the greatest risk of adverse pregnancy outcomes [7]. While maternal overweight likely affects caries development in the child, the mechanism by which this happens is yet to be elucidated [8].
Development of the primary tooth germ commences at the end of the 5th week of gestation with mineralization starting during the 13th week and continuing on throughout pregnancy to the end of the first year of life for primary teeth and up to 6 years of age for permanent teeth [10]. During this period of tooth development, prenatal exposure to tobacco smoke can negatively affect the quality (i.e. tooth calcification and mineralization) [11] and subsequent timing of tooth eruption [12, 13]. Ntani and colleagues reported that children whose mothers smoked during pregnancy had more teeth erupted at ages 1 and 2 compared to similarly aged children whose mothers did not smoke during pregnancy [13] and suggested that premature tooth eruption likely lie on the causal pathway between maternal smoking during pregnancy and subsequent caries development. In addition, smoking during pregnancy [14], and pregnancy adiposity [9] are associated with low-birth weight and prematurity, factors reported to increase the risk of developmental enamel defects like hypo-mineralization and hypo-calcification [11, 15]. These developmental tooth defects increases tooth susceptibility to cariogenic bacteria [16, 17] in the presence of fermentable carbohydrates [11].
Maternal smoking during pregnancy, exposes the growing fetus to chemical toxins including nicotine through its direct metabolite cotinine which cross the placenta to accumulate in fetal tissues [18]. Furthermore, prenatal exposure to tobacco smoke alters fetal blood flow and protein metabolism, resulting in the accumulation of chemical toxins in the mother and developing fetus [1]. While smoking throughout pregnancy likely increases offspring caries experience, the critical exposure period appears to be the first trimester of pregnancy. Indeed, maternal smoking and weight [8] in the first trimester, were independently associated with increases in subsequent dental caries risk in children [19] and teenagers [8] more so than exposures occurring during other periods of pregnancy. This finding has not been independently replicated in other population groups and there are methodologic limitations on how timing during pregnancy was assessed.

References Cited

1. Zhou S, Rosenthal DG, Sherman S, Zelikoff J, Gordon T, Weitzman M: Physical, behavioral, and cognitive effects of prenatal tobacco and postnatal secondhand smoke exposure. Curr Probl Pediatr Adolesc Health Care 2014, 44(8):219-241.
2. Jurado D, Munoz C, Luna Jde D, Munoz-Hoyos A: Is maternal smoking more determinant than paternal smoking on the respiratory symptoms of young children? Respir Med 2005, 99(9):1138-1144.
3. Metsala J, Kilkkinen A, Kaila M, Tapanainen H, Klaukka T, Gissler M, Virtanen SM: Perinatal factors and the risk of asthma in childhood--a population-based register study in Finland. Am J Epidemiol 2008, 168(2):170-178.
4. Chung KC, Kowalski CP, Kim HM, Buchman SR: Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate. Plast Reconstr Surg 2000, 105(2):485-491.
5. Jaakkola JJ, Gissler M: Maternal smoking in pregnancy as a determinant of rheumatoid arthritis and other inflammatory polyarthropathies during the first 7 years of life. Int J Epidemiol 2005, 34(3):664-671.
6. Mizutani T, Suzuki K, Kondo N, Yamagata Z: Association of maternal lifestyles including smoking during pregnancy with childhood obesity. Obesity (Silver Spring) 2007, 15(12):3133-3139.
7. Djelantik AA, Kunst AE, van der Wal MF, Smit HA, Vrijkotte TG: Contribution of overweight and obesity to the occurrence of adverse pregnancy outcomes in a multi-ethnic cohort: population attributive fractions for Amsterdam. BJOG 2012, 119(3):283-290.
8. Julihn A, Ekbom A, Modeer T: Maternal overweight and smoking: prenatal risk factors for caries development in offspring during the teenage period. Eur J Epidemiol 2009, 24(12):753-762.
9. Lawlor DA, Relton C, Sattar N, Nelson SM: Maternal adiposity--a determinant of perinatal and offspring outcomes? Nat Rev Endocrinol 2012, 8(11):679-688.
10. Hujoel PP, Lingstrom P: Nutrition, dental caries and periodontal disease: a narrative review. J Clin Periodontol 2017, 44 Suppl 18:S79-s84.
11. Caufield PW, Li Y, Bromage TG: Hypoplasia-associated severe early childhood caries--a proposed definition. J Dent Res 2012, 91(6):544-550.
12. Aligne CA, Moss ME, Auinger P, Weitzman M: Association of pediatric dental caries with passive smoking. JAMA 2003, 289(10):1258-1264.
13. Ntani G, Day PF, Baird J, Godfrey KM, Robinson SM, Cooper C, Inskip HM, Southampton Women's Survey Study G: Maternal and early life factors of tooth emergence patterns and number of teeth at 1 and 2 years of age. Journal of Developmental Origins of Health and Disease 2015, 6(4):299-307.
14. Jaddoe VW, Troe EJ, Hofman A, Mackenbach JP, Moll HA, Steegers EA, Witteman JC: Active and passive maternal smoking during pregnancy and the risks of low birthweight and preterm birth: the Generation R Study. Paediatr Perinat Epidemiol 2008, 22(2):162-171.
15. Vello MA, Martinez-Costa C, Catala M, Fons J, Brines J, Guijarro-Martinez R: Prenatal and neonatal risk factors for the development of enamel defects in low birth weight children. Oral Dis 2010, 16(3):257-262.
16. Plonka KA, Pukallus ML, Barnett AG, Holcombe TF, Walsh LJ, Seow WK: A longitudinal case-control study of caries development from birth to 36 months. Caries Res 2013, 47(2):117-127.
17. Salanitri S, Seow WK: Developmental enamel defects in the primary dentition: aetiology and clinical management. Aust Dent J 2013, 58(2):133-140; quiz 266.
18. Maritz GS: Nicotine and lung development. Birth Defects Res C Embryo Today 2008, 84(1):45-53.
19. Tanaka K, Miyake Y, Nagata C, Furukawa S, Arakawa M: Association of prenatal exposure to maternal smoking and postnatal exposure to household smoking with dental caries in 3-year-old Japanese children. Environ Res 2015, 143(Pt A):148-153.
20. Greenland S, Pearl J, Robins JM: Causal diagrams for epidemiologic research. In: Epidemiology. Volume 10, edn. United States; 1999: 37-48.
21. Robins JM, Hernan MA, Brumback B: Marginal structural models and causal inference in epidemiology. Epidemiology 2000, 11(5):550-560.
22. Suissa S: Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008, 167(4):492-499.
23. Matok I, Azoulay L, Yin H, Suissa S: Immortal time bias in observational studies of drug effects in pregnancy. Birth Defects Res A Clin Mol Teratol 2014, 100(9):658-662.
24. Tanaka S, Shinzawa M, Tokumasu H, Seto K, Tanaka S, Kawakami K: Secondhand smoke and incidence of dental caries in deciduous teeth among children in Japan: population based retrospective cohort study. Bmj 2015, 351:h5397.
25. Tanaka K, Miyake Y, Sasaki S: The effect of maternal smoking during pregnancy and postnatal household smoking on dental caries in young children. J Pediatr 2009, 155(3):410-415.
26. Majorana A, Cagetti MG, Bardellini E, Amadori F, Conti G, Strohmenger L, Campus G: Feeding and smoking habits as cumulative risk factors for early childhood caries in toddlers, after adjustment for several behavioral determinants: a retrospective study. BMC Pediatr 2014, 14:45.
27. Claudia C, Ju X, Mejia G, Jamieson L: The relationship between maternal smoking during pregnancy and parental-reported experience of dental caries in Indigenous Australian children. Community Dent Health 2016, 33(4):297-302.
28. Iida H, Auinger P, Billings RJ, Weitzman M: Association between infant breastfeeding and early childhood caries in the United States. Pediatrics 2007, 120(4):E944-E952.

Impact of research: 
This study will add to the body of knowledge on the broader topic of the adverse health effects in the offspring of smoking during pregnancy and pre-pregnancy weight. Furthermore, areas of improvements for future research can be identified and refined accordingly. Such as using cotinine to assess maternal smoking instead of relying on self-report and conducting oral examinations on all children if there are significant differences between children who were examined and those that were not.
Date proposal received: 
Friday, 15 September, 2017
Date proposal approved: 
Wednesday, 20 September, 2017
Keywords: 
Epidemiology, Obesity, Dental caries, BMI, Cohort studies - attrition, bias, participant engagement, ethics, Dental, Environment - enviromental exposure, pollution, Offspring, Statistical methods

B2957 - Severe Mental Illness Cardiovascular Health - 20/09/2017

B number: 
B2957
Principal applicant name: 
Esther Walton | University of Bristol - IEU
Co-applicants: 
Title of project: 
Severe Mental Illness & Cardiovascular Health
Proposal summary: 

The largest meta-analysis to date found that risk of dying from cardiovascular disease (CVD, including conditions such as coronary heart disease, cerebrovascular disease and congestive heart failure) is 85% higher in people with severe mental illness (SMI; Correll et al., 2017). According to that study, factors which increased risk for cardiovascular disease in SMI patients included antipsychotic use and higher body mass index (BMI).
However, the interplay between SMI and CVD and their risk factors is complex. Reverse causation or confounding might compromise our ability to draw causal conclusions and in fact, no study to date has addressed the causal effects between SMI and CVD or the potentially mediating role of factors such as BMI.
The observed association between SMI and CVD also points towards shared biological correlates. Epigenetic processes such as DNA methylation, can present a potential biological mechanism linking SMI and CVD. DNA methylation signatures have been robustly linked to SMI and SMI / CVD risk factors (Barker, Walton, & Cecil, n.d.; Dick et al., 2014; Joubert et al., 2016; Kato et al., 2015), but no study to date has investigated the epigenetic overlap between CVD and SMI.

Impact of research: 
Findings could lend novel insights into the role of DNA methylation in the link between severe mental illness and cardiovascular disease.
Date proposal received: 
Wednesday, 20 September, 2017
Date proposal approved: 
Wednesday, 20 September, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, cardiovascular, Epigenetics, GWAS, Metabolomics, Cardiovascular, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., mental health

B2951 - Language and communication in childhood and their relationship to adult life chances an analysis of the ALSPAC cohort - 20/09/2017

B number: 
B2951
Principal applicant name: 
Yvonne Wren | University of Bristol (UK)
Co-applicants: 
Professor Sue Roulstone, Professor James Law, Dr Judy Clegg, Dr Jon Heron, Professor Tim Peters, Dr Rebecca Kandiyali
Title of project: 
Language and communication in childhood and their relationship to adult life chances: an analysis of the ALSPAC cohort
Proposal summary: 

The development of language and communication (L&C)skills in young children is important. When children start school at the age of 4 to 5 years, they need to be able to understand what is said to them, be able to talk and express themselves and to be able to communicate and interact with other children and adults. If a child has these skills, they will be successful in learning to read and write and in their subsequent educational progress and attainment during their school careers. As teenagers and adults, the ability to communicate effectively is essential to their life chances in terms of securing employment, living independently and maintaining relationships and wellbeing. Children who are slower to develop their L&C skills or have specific difficulties with this are known to have particular life-long difficulties, not just in their educational attainment but in other areas of their lives. In adolescence and adult life, this includes poor educational attainment, limited life chances in terms of employment prospects and independence and their wellbeing and quality of life including a higher chance of experiencing mental health difficulties and being at risk of offending behaviour. This evidence between psychosocial outcomes and L&C development is limited as it comes from very small studies of children with identified impairments. It is not known whether these impacts on psychosocial outcomes are more widespread and evident in children whose L&C development is below average and therefore less advanced than their peers, but who would not be described as language impaired per se. Understanding the relationship between childhood L&C development and psychosocial outcomes in adulthood will help determine the potential costs involved with suboptimal L&C development and the potential benefits to life chances of interventions which promote childhood L&C development.

This study will consider the L&C development and abilities of individuals through childhood, adolescence and adult life and find out how their competence in these impact on their psychosocial outcomes, as indicated by measures of quality of life and wellbeing. This study will collect new data and also use existing data from ALSPAC. This study will collect new data about the L&C, using innovative technology to collect samples via computers and phones, and use this to explore the range of L&C skills in the adult population. Using existing data within the dataset, this study will explore the range of psychosocial outcomes that are evident within the sample and consider these in relation to childhood and adult L&C abilities alongside other known risk factors. Finally, we will consider the costs associated with varying levels of L&C abilities in childhood and adulthood and the potential benefits for individuals and society of interventions to promote L&C skills.

Impact of research: 
This research will be the first study to use a large general population-based cohort to understand the trajectory of language and communication ability and competence in adult psychosocial outcomes. The research will analyse existing data but will be particularly innovative in designing research methods to capture new data to measure language and communication ability and psycho-social functioning in adults in a large cohort study with a high retention rate such that between 4,000 and 4,5000 participants in their mid twenties are still involved. The large scale of the research means that new data collection has to be innovative in order to be both highly informative as well as economical. The new data will be collected using online measures, negating the need for costly face-to-face assessment. This will be the first research study to collect new adult data of language and communication ability and competence, and psychosocial functioning in a UK population study, and to analyse this in relation to existing data from birth into adult life in a large general population-based cohort. The main aim of this research is to understand the impact that L&C development in childhood and L&C competence in adulthood have on psychosocial outcomes for adults. Many individuals experience L&C delay and, whilst there is a greater risk of low outcomes for this group as a whole, many go on to live successful lives with positive psychosocial outcomes. Currently, we do not know which individuals who experience suboptimal L&C development in childhood will go on to have positive psychosocial outcomes in adulthood and which do not. Through understanding the relationship between childhood and adulthood L&C competence and ability and psychosocial outcomes in adulthood, we will be able to identify which factors promote resilience in individuals at risk of poor outcomes in adulthood. This will impact on our understanding of which factors can be developed and encouraged in young people to promote resilience in individuals with a history of language impairment in childhood.
Date proposal received: 
Sunday, 10 September, 2017
Date proposal approved: 
Wednesday, 13 September, 2017
Keywords: 
Social Science, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cognitive impairment, Learning difficulty, Mental health, Speech/language problem, Statistical methods, Childhood - childcare, childhood adversity, Cognition - cognitive function, Communication (including non-verbal), Development, Linkage, Intelligence - memory, Psychology - personality, Speech and language, Statistical methods

B2924 - Genetics of MHO/MUNW in children and adolescents - 12/09/2017

B number: 
B2924
Principal applicant name: 
Anna Viitasalo | MD, PhD
Co-applicants: 
Tuomas Kilpeläinen
Title of project: 
Genetics of MHO/MUNW in children and adolescents
Proposal summary: 

Many obese individuals remain free of cardiometabolic comorbidities. These individuals are often labeled as metabolically healthy obese (MHO). Obesity has heterogenic nature also in children and adolescents.

Impact of research: 
This novel and timely research will provide valuable information on about the link between adiposity and its complications in childhood populations.
Date proposal received: 
Wednesday, 2 August, 2017
Date proposal approved: 
Tuesday, 12 September, 2017
Keywords: 
Genetics, Obesity, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., BMI, Cardiovascular, Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Puberty

B2949 - Encouraging Effective Participant Engagement in Cohort Studies EEPECS - 22/09/2017

B number: 
B2949
Principal applicant name: 
Richard Huxtable | University of Bristol (UK)
Co-applicants: 
Prof. Jean Golding, Dr Jonathan Ives, Miss Cynthia Ochieng
Title of project: 
Encouraging Effective Participant Engagement in Cohort Studies (EEPECS)
Proposal summary: 

Participant engagement in cohort studies has been argued to be a key factor in building trust in the cohort and facilitating long-term retention. Despite the acknowledged benefits of engaging participants in such studies, little research has been conducted to understand what this engagement looks like and how it should be conducted. The proposed study seeks to fill this knowledge gap. Following on from CO’s doctoral study that explored participants’ experiences and perception of their engagement with ALSPAC, the proposed study will: (1) review ALSPAC’s engagement and identify key messages present in their communication with participants; (2) conduct a qualitative study into (ALSPAC and other) cohort personnel’s experiences and perceptions of participant engagement; and (3) combine insights from participants’ perspectives (generated from CO’s previous doctoral research) with insights from the ALSPAC material and the cohort personnel perspectives to formulate a theoretical framework for participant engagement that will explain how and why certain strategies are more or less successful, more or less (un)ethical, and more or less (un)appealing to participants and researchers. In so-doing, this study will produce results that meet CLOSER’s objective to build skills in the management of cohort studies.

Impact of research: 
The outcome of the proposed study will be the development of a theoretical framework to guide participant engagement in cohort and longitudinal studies. The study will therefore assist CLOSER in building the capacity of cohort studies and stimulating their engagement with their participants and the general public. Anticipated follow-on work involves translating the framework into practice in different cohorts, followed by an evaluation of its impact on participant engagement in these cohort studies.
Date proposal received: 
Thursday, 7 September, 2017
Date proposal approved: 
Tuesday, 12 September, 2017
Keywords: 
Social Science, Qualitative study, Social science

B2944 - Genetics for social scientists facilitating multidisciplinary research in CLOSER - 06/09/2017

B number: 
B2944
Principal applicant name: 
Meena Kumari | University of Essex (UK)
Co-applicants: 
Michaela Benzeval
Title of project: 
Genetics for social scientists: facilitating multidisciplinary research in CLOSER
Proposal summary: 

The CLOSER studies are composed of those established to examine clinical and biological phenomena or social studies supplemented with biomarker and genetic data. A recent overview of the genetic data indicates that data are available in CLOSER from over n=30,000 participants. However there is wide variation in practice across the CLOSER studies at a number of different levels which may represent barriers for those wishing to apply for these data. These include variation in genetic data sharing processes, differences in information and participant consent and genotyping platforms, which can be multiple within between and within studies. This can represent a challenge for inter-disciplinary research, in particular for social science researchers interested in accessing genetic data. Here we propose to catalogue meta-data (consent and response rates) around the genetic data available in each of the CLOSER studies; create a guidance document to enable researchers to access genetic data – this document should additionally serve to reduce the workload for the data sharing teams and finally to provide a demonstration project of the kind of analyses that can be done with the CLOSER studies on social-biological research, an important ESRC priority area. In particular we will include an in-depth focus on the development of genetic risk scores – here our proposed example is for body mass index and its interaction with social position. Finally we wish to examine the new and growing concern in genetics research to adjust for sample bias or selection by social position in the analysis.

Impact of research: 
This project will have capacity building impact and open up the possibility of scientific impact by create training materials for the research community involved in ‘biosocial’ research agenda as outlined by the ESRC strategy. We anticipate that a single source guide on the genetic data should not only serve to facilitate cross disciplinary research but also to reduce work load for data dissemination and support teams in each of the studies. Further we will provide a guide to the principals of polygenic risk score generation. Studies with genetic data in CLOSER and METADAC are supportive of this proposal, contributing to engagement and commitment. As a result of the project, we will provide materials that should encourage biosocial research across CLOSER. We will present findings at conferences, which will raise awareness of research opportunities within and across CLOSER and other studies.
Date proposal received: 
Thursday, 31 August, 2017
Date proposal approved: 
Wednesday, 6 September, 2017
Keywords: 
Social Science, Obesity, GWAS, Social science

B2945 - Defining ADHD and conduct disorder using linked electronic primary care data - 06/09/2017

B number: 
B2945
Principal applicant name: 
Rosie Cornish | ALSPAC (UK)
Co-applicants: 
Mr Andy Boyd, Professor Ann John, Professor Sinead Brophy, Professor Ronan Lyons, Professor Emla Fitzsimons
Title of project: 
Defining ADHD and conduct disorder using linked electronic primary care data
Proposal summary: 

Longitudinal studies like ALSPAC usually suffer from missing data arising through non-response. This issue can be partly addressed by linking to routine data sources, since individuals who are missing from the study data will be present in such datasets. Measures created using routine data could be used in place of the missing study outcomes or used to impute the missing values. However, in order for them be used in this way, it is important to know how outcomes recorded in these datasets relate to outcomes recorded in the longitudinal studies. To our knowledge, no studies to date have validated measures for defining ADHD or conduct disorder within routine electronic primary care data.

The Strength and Difficulties Questionnaire (SDQ) has been widely used to measure child psychopathology both in research studies and in clinical practice. It has been shown to be a valid tool for identifying children with attention deficit hyperactivity disorder (ADHD) and conduct disorder (Goodman et al, 2000a). The Development and Well-being Assessment (DAWBA) is a tool that can be used to ascertain whether an individual meets DSM IV (American Psychiatric Association, 1994) diagnostic criteria for a range of psychiatric disorders, including ADHD and conduct disorder (Goodman et al, 2000b)

SDQ data have been collected in both ALSPAC and the Millennium Cohort Study (MCS). ALSPAC has also collected DAWBA data. Both studies have also linked to primary care data on a subset of participants. As such, these two studies provide a unique opportunity to validate measures of ADHD and conduct disorder derived using electronic primary care data against previously validated measures.

Impact of research: 
The outcomes of this project will support research in ADHD and conduct disorder using routine health data by demonstrating how to best identify cases using electronic primary care data and will highlight the availability of data on ADHD and conduct disorder data in these two cohorts, including measures derived from linked primary care data.
Date proposal received: 
Friday, 1 September, 2017
Date proposal approved: 
Wednesday, 6 September, 2017
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, health informatics, ADHD Conduct disorder Electronic primary care data

B2946 - Scoping existing dietary data available in CLOSER to support cross-cohort research questions - 06/09/2017

B number: 
B2946
Principal applicant name: 
Jane Maddock | MRC Lifelong Health and Ageing at UCL
Co-applicants: 
Prof Rebecca Hardy
Title of project: 
Scoping existing dietary data available in CLOSER to support cross-cohort research questions
Proposal summary: 

Health related behaviours across the life course, including dietary habits, play an important role in health and ageing (1-3). However, the measurement and analysis of diet in longitudinal epidemiological studies is extremely challenging. An individual’s diet is the result of the current zeitgeist, their social, economic and cultural circumstances and, it varies in relation to age (2, 4, 5). A person’s dietary intake will also vary according to season, day of week and has considerable random variation (6). The aim in epidemiological studies is to capture an individual’s consistent long-term diet in the context of this variation. Objective measures of dietary intake, such as direct observation, are costly and carry significant participant and researcher burden (7). Therefore self-reported measures of dietary intake have been developed. A number of these are used in the CLOSER cohorts e.g. food frequency questionnaires (FFQs) in ALSPAC, National Child & Development Study (NCDS), 1970 British birth cohort (BCS70), Southampton Women's Survey (SWS), Hertfordshire cohort study (HCS) and diet diaries in National Survey of Health and Development (NSHD), ALSPAC and SWS. However, it remains difficult to accurately capture habitual dietary intake, and there is always the possibility of over- or under-reporting (7). Validation studies of these instruments in EPIC-Norfolk demonstrated that correlation between dietary biomarkers and a 7-day food diary was better than correlation with an FFQ (8, 9). However, each of these methods also have specific pros and cons. For example, FFQs can capture foods consumed irregularly but reporting is limited to the items contained in the food list designed for the study (7). In food diaries, all food consumed at the time of consumption is recorded, but it may miss foods not eaten regularly (7). Within-method differences e.g. a 3-day food diary versus a 7-day food diary adds to heterogeneity in dietary measurement. Results from each method can therefore be slightly different. For example, one study found that macronutrient estimates from FFQs are higher compared with estimates from a 7-day or 16-day food diary using data from EPIC-Norfolk (8). In ALSPAC, slightly different dietary patterns in childhood were produced depending on the dietary assessment used (10).

Nutritional epidemiology has advanced during the time span of the CLOSER cohorts. An individual’s diet contains many foods/nutrients that interact or can act in synergy to influence health. Nutritional epidemiology is moving away from analysing associations of health outcomes with individual foods and nutrients towards dietary pattern analysis (11). Analyses of data in the CLOSER cohorts reflect this trend (10, 12-14). Comparing dietary intake across CLOSER cohorts would provide powerful information about longitudinal and secular trends. For example, a previous comparison of data from a 24-hour recall in NSHD and a 4 day food diary in the National Diet and Nutrition Survey, found that children in 1950 consumed a diet that was higher in fat, but was considered healthier than children in the 1990s (15). Clarifying and documenting the methodological differences in dietary assessment between the CLOSER cohorts is an essential step for any cross-cohort dietary pattern comparisons.

Comparing relationships between diet and health outcomes across cohorts will provide insight into potential cohort specific or consistent associations. Allostatic load (AL) is one health outcome that has been harmonised across the CLOSER cohorts. AL is a measure of cumulative biological dysregulation across body systems (16) which has been associated with mortality and frailty (16-18). Environmental stressors, including diet, have been proposed as contributors to AL however evidence is limited (19-24). Supporting evidence from large, longitudinal studies will help to confirm the link between diet and AL. Therefore, examining the association between diet and AL across the CLOSER cohorts would be a significant contribution to this effort.

References
1. Mathers JC. Nutrition and ageing: knowledge, gaps and research priorities. Proceedings of the Nutrition Society. 2013;72(2):246-50.
2. Kiefte-de Jong JC, Mathers JC, Franco OH. Nutrition and healthy ageing: the key ingredients. Proceedings of the Nutrition Society. 2014;73(2):249-59.
3. Ben-Shlomo Y, Cooper R, Kuh D. The last two decades of life course epidemiology, and its relevance for research on ageing. International journal of epidemiology. 2016;45(4):973-88.
4. De Irala-Estevez J, Groth M, Johansson L, Oltersdorf U. A systematic review of socio-economic differences in food habits in Europe: consumption of fruit and vegetables. European journal of clinical nutrition. 2000;54(9):706.
5. Kirkpatrick SI, Collins CE. Assessment of nutrient intakes: Introduction to the Special Issue. Multidisciplinary Digital Publishing Institute; 2016.
6. Willett W. Nature of Variation in Diet. In: Willett W, editor. Nutritional Epidemiology New York: Oxford University Press; 2013.
7. Medical Research Council. Diet, Anthropometry and Physical Activity (DAPA) Measurement Toolkit 2015 [cited 2017 15 August].
8. Bingham SA, Gill C, Welch A, Cassidy A, Runswick SA, Oakes S, et al. Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers. International journal of epidemiology. 1997;26(suppl_1):S137.
9. Day NE, McKeown N, Wong M-Y, Welch A, Bingham S. Epidemiological assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium. International Journal of Epidemiology. 2001;30(2):309-17.
10. Emmett PM, Jones LR, Northstone K. Dietary patterns in the avon longitudinal study of parents and children. Nutrition reviews. 2015;73(suppl_3):207-30.
11. Hu FB. Dietary pattern analysis: a new direction in nutritional epidemiology. Current opinion in lipidology. 2002;13(1):3-9.
12. Emmett P. Dietary assessment in the Avon longitudinal study of parents and children. European journal of clinical nutrition. 2009;63(S1):S38.
13. Prynne C, Paul A, Mishra G, Hardy R, Bolton-Smith C, Wadsworth M. Sociodemographic inequalities in the diet of young children in the 1946 British birth cohort. Public health nutrition. 2002;5(6):733-45.
14. Mishra G, McNaughton S, Bramwell G, Wadsworth M. Longitudinal changes in dietary patterns during adult life. British Journal of Nutrition. 2006;96(4):735-44.
15. Prynne C, Paul A, Price G, Day K, Hilder W, Wadsworth M. Food and nutrient intake of a national sample of 4-year-old children in 1950: comparison with the 1990s. Public health nutrition. 1999;2(4):537-47.
16. Seeman TE, McEwen BS, Rowe JW, Singer BH. Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proceedings of the National Academy of Sciences. 2001;98(8):4770-5.
17. Gale CR, Booth T, Starr JM, Deary IJ. Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936. J Epidemiol Community Health. 2015:jech-2015-205789.
18. Gruenewald TL, Seeman TE, Karlamangla AS, Sarkisian CA. Allostatic load and frailty in older adults. Journal of the American Geriatrics Society. 2009;57(9):1525-31.
19. McEwen BS. Stress, adaptation, and disease: Allostasis and allostatic load. Annals of the New York Academy of Sciences. 1998;840(1):33-44.
20. Frei R, Haile SR, Mutsch M, Rohrmann S. Relationship of serum vitamin D concentrations and allostatic load as a measure of cumulative biological risk among the US population: a cross-sectional study. PloS one. 2015;10(10):e0139217.
21. Rosenberg N, Park CG, Eldeirawi K. Relationship of serum carotenoid concentrations with allostatic load as a measure of chronic stress among middle-aged adults in the USA. Public health nutrition. 2015;18(2):313-21.
22. Mattei J, Bhupathiraju S, Tucker KL. Higher adherence to a diet score based on American Heart Association recommendations is associated with lower odds of allostatic load and metabolic syndrome in Puerto Rican adults. The Journal of nutrition. 2013;143(11):1753-9.
23. Mattei J, Noel SE, Tucker KL. A meat, processed meat, and French fries dietary pattern is associated with high allostatic load in Puerto Rican older adults. Journal of the American Dietetic Association. 2011;111(10):1498-506.
24. Kusano Y, Crews DE, Iwamoto A, Sone Y, Aoyagi K, Maeda T, et al. Allostatic load differs by sex and diet, but not age in older Japanese from the Goto Islands. Annals of human biology. 2016;43(1):34-41.

Impact of research: 
Collating complicated dietary information across the cohorts and the development of harmonised dietary measures (e.g. food groups, macronutrient intakes, pre-defined dietary pattern) will support the dissemination of nutrition expertise to interdisciplinary CLOSER data users and highlight best use of dietary data in future studies. This will also ensure that the CLOSER cohorts are prepared for future advances in nutritional epidemiology e.g. comparing traditional measures with biomarkers of dietary intake using metabolomics. Examining diet with AL will provide better understanding of the pathways that link diet throughout the life course with aging. This has the potential to inform the timing of interventions to improve healthy ageing.
Date proposal received: 
Friday, 1 September, 2017
Date proposal approved: 
Wednesday, 6 September, 2017
Keywords: 
Epidemiology

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