Proposal summaries
B403 - Being 16 Camera Project - 15/09/2006
No outline received
B401 - Longitudinal modelling of energy imbalance based on changes in body composition in ALSPAC participants 9-13 years - 15/09/2006
Obesity is a chronic disorder of energy balance: the amount of energy being spent must remain less than the amount of energy consumed for a long period of time for obesity to develop. The traditional paradigm for the development of obesity is that a process of 'creeping weight gain' occurs1, and that the rate or degree of positive energy balance is very small - in both adults and children - when considered over long periods (equivalent to perhaps as little as 50 kcal/day)1,2. This paradigm translates directly to public health messages aimed at persuading individuals to make small lifestyle changes in order to prevent obesity ("eat a little less, do a little more")1. The paradigm has been challenged by the finding that, in at least one population at high risk of obesity (Latino children, adolescents, and young adults in Houston Texas3), rates of positive energy balance are typically very much higher. In that study, the median positive energy balance was equivalent to greater than 200kcal/day for a year3.
B400 - Gene and environmental influences on childhood asthma STELAR Study Team for Early Life Asthma Research Collaboration - 14/09/2006
No outline received
B396 - DANVA Analysis - 11/09/2006
(No outline received).
B395 - Relationship between Thyroid Status and Skeletal Development - 11/09/2006
(No outline received).
B394 - MTHFR C677T Genotype and Obesity - 11/09/2006
TheMTHFRTT genotype is associated with an increased frequency of obesity relative to the CC genotype, due to a reduction in availability of folate for methylation observed with this genotype.
We plan to examine the association between the MTHFR genotype in 4 distinct populations within 3 Cohort studies; The British Women's Heart and Health Study, Avon longitudinal study of Parents and Children (2 populations: mothers and children) and Copenhagen City Heart Study.
B391 - Social Deprivation and Respiratory Health - A Lifecourse Perspective - 04/09/2006
This project will address the question of health inequalities, by addressing the relationships between measures of socio-economic deprivation and respiratory health, particularly wheezing illnesses, asthma and lung function.The first part of the study will focus on the detailed information on respiratory health and socio-economic factors in the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine the association of socio-economic deprivation and respiratory outcomes during childhood.We will further investigate these associations by attempting to identify explanatory variables, including lifestyle (smoking, diet) and environmental exposures.Observed associations will then be examined using a lifecourse epidemiological approach to investigate whether associations that we observe in a contemporary population of children (ALSPAC) are reproducible across previous generations in the United Kingdom and whether deprivation in childhood is associated with adult respiratory outcomes, independently of adult socio-economic status.In turn, this will allow us to explore the possible effects of social mobility on adult respiratory health. The project brings together expertise on the analysis of inequalities in health from an economics perspective, with a focus on measures of access to resources, and the exploitation of dynamics in data and the use of GIS tools to map local features to individuals (in the Department of Economics), childhood respiratory epidemiology, including assessment of asthma and lung function in a longitudinal birth cohort sample (Department of Community-based Medicine) and the multidisciplinary specialty of lifecourse epidemiology, including access to archived information on other existing cohorts (Department of Social Medicine).Therefore, this is a unique opportunity to build a global, comprehensive picture of the factors associated with socio-economic deprivation in the U.K. and their potential effects on an important aspect of public health.
Obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD) are among the commonest chronic health problems of children and adults in the United Kingdom. However, a review of the evidence on inequalities in Britain did not mentionasthma as a health issue related to poverty. Within countries there have been studies that have examined the relationship between socio-economic status and prevalence of asthma. While there does appear to be a consistent relationship between allergy prevalence and high socio-economic status, there is conflicting evidence with regard to asthma with studies showing increased or decreased prevalence in higher socio-economic groups and others showing no socio-economic gradient. However, one of the problems of interpreting these studies is that many of them are based on cross-sectional surveys and results may be inconsistent across time. For example, we have previously demonstrated differences in social factors associated with wheeze between infants and adults. This may relate to differentpathological aetiologies of wheezing in these two populations.Wheezing in infancy is associated with respiratory tract infection on a background of abnormal airway development, as evidenced by reduced lung function shortlyafter birth. Social factors, including exposure to tobacco smoke, have been demonstrated to be strongly associated with reduced airway function in infancy and a tendency to wheeze in the first few years after birth and factors associated with deprivation, such as crowded living conditions, larger family size and a reduced tendency to breast feeding will tend to increase the risk of respiratory infections. Although wheezing tends to resolve in the majority of these children by the age of 3 years, there is increasing interest in the long-term implications of impaired lung function in infancy and the possible relationship with COPD in adult life. Although COPD is generally regarded as a smoking-related illness, only a minority of active smokers develop the condition and, in observational studies that have examined early life factors, these have been shown to have a greater effect on COPD mortality than active smoking in later life. Therefore, in order to fully understand the nature of associations between markers of socio-economic deprivation and respiratory health and diseases, it is necessary to design studies that have the capacity to examine short and long term outcomes, preferably in the context of a longitudinal cohort design. The Avon Longitudinal Study of Parents and Children is a birth cohort study that has followed a population of children, recruited during their mothers' pregnancies with expected dates of delivery between April 1991 and December 1992. The study has included repeat questionnaires about respiratory symptoms at approximately annual intervals since birth and has objective measurements of lung function at 8 1/2 years of age. During the course of the proposed project, a further measurement of lung function will be available at 15 1/2 years (MRC funded). The ALSPAC study has also collected detailed information on lifestyle and environment (housing type, type of heating/cooking used, reported damp or mould in the home, household cleaning product use, parental smoking, and detailed dietary diaries from the mother and child). This presents the opportunity to carry out a uniquely detailed study of socio-economic influences on respiratory symptoms and function from birth to adolescence. To address the longer term respiratory health questions, we will use the approach of lifecourse epidemiology to investigate exposures at different stages of development that may contribute to the risk of diseases in adults, either by accumulation of exposure over time or by exposures acting at critical periods of development, or by interactions of these. The Department of Social Medicine, University of Bristol has extensive expertise in lifecourse epidemiological approaches using a combination of contemporary and historical cohort studies. We aim to study the Boyd-Orr cohort which was based on the Carnegie survey of diet and health (1937-9) of 4973 children and has information on socio-economic factors, diet and growth in childhood and respiratory follow up including MRC respiratory questionnaire responses and spirometry. We would also seek to collaborate with the 1958 and 1970 British birth cohort studies, which have also collected information on respiratory outcomes.
B449 - Translating genome-wide association data from the WTCCC study into biological and clinical insights in type 2 diabetes - 01/09/2006
Aim.
To test the hypothesis that variation in genes in key beta-cell pathways increases the risk of type 2 diabetes.
Aim: To use large-scale genome wide association data from the Wellcome Trust Case Control Consortium (WTCCC) as a platform for a systematic assessment of the role of variation in beta-cell genes in the aetiology of type 2 diabetes.
B308 - Children in Poverty aspirations expectations and attitudes to education - 01/09/2006
Children from deprived homes emerge from our schools with substantially lower levels of educational attainment. These educational deficits emerge early in children's lives, even before entry into school and widen throughout childhood.
But little is known about how family background affects education attainment. This project will consider the influences on children's skill development, in its broadest sense, focussing particularly on soft skills, and on attitudes to education amongst children from low-income backgrounds
B389 - Use of Genetic-Variation to Explore Associations between Early Life Nutrition - 21/08/2006
To determine whether exposure to specific dietary factors in utero and infancy influences cognition.
Specific Hypotheses:
1) Suboptimum levels of specific nutrients such as folate and omega-3 fatty acids in utero lead to impaired neurodevelopment and low cognitive ability.
2) Polymorphisms in genes which metabolise nutrients are associated with neurodevelopment in infancy and can be used to infer causal relationships between specific nutrients and cognition.
3) Maternal genotype and corresponding offspring genotype, jointly determine neurodevelopment in infancy and childhood. Associations with maternal genotype, independent of offspring genotype, will support the role of the prenatal environment.
Neuroanatomical and neurophysiological studies show that brain development occurs most rapidly during fetal development and in infancy. Nutrition is probably the single greatest environmental influence both on the fetus and neonate, and plays a necessary role in the maturation and functional development of the central nervous system. Therefore a lack of any nutrient required for brain development may be related to neurodevelopmental diseases such as autism as well as influencing general cognition. Nutrients found to be lacking in the mothers' diet could, if shown to be related to brain development, be modified to prevent disease and ensure that the childs' cognitive ability is not impaired.
We plan to:
1) Genotype mothers and their offspring with respect to candidate polymorphisms which influence nutrient intake, metabolism, transport or cellular uptake.
2) Determine associations between the above maternal and infant polymorphisms and childhood cognition.
3) Stratifying by offspring genotype, determine associations between maternal genotype and offspring cognition.
4) Investigate whether the above polymorphisms are associated with cigarette smoking, socioeconomic status, reproductive factors and other potential confounders in the mothers, to confirm that developmental outcome associations with genotypes are not confounded.
Genotype analysis
Variation in genes which alter the availability of specific nutrients will be exploited in this project. Suitable candidate genes include those which are; a) associated with nutrient intake, such as the lactase gene, polymorphisms of which determine lactose intolerance and therefore intake of lactose b) involved in nutrient metabolism, for example there are several enzymes involved in the biosynthesis of the omega-3 fatty acid DHA from its' precursors in the diet including cycloxygenase (COX), lipoxygenase (LOX) and delta-5 desaturase, c) important in the transport and internalization of nutrients into target cells, such as the choline transporter (CHT1) gene. Genotyping of SNPs will be carried by K-Biosciences (http://www.kbioscience.co.uk).
Outcome measurements
The primary outcome will be the Wechsler Intelligence Scale for Children (WISC)-III, which is a UK measure of cognitive ability (IQ) measured at the focus clinic at age 8 1/2 (score available for 7188 children). Education is strongly influenced by political and social factors and is therefore less likely to be due to mothers' diet, however, educational scores will be secondary outcomes in this study as education is likely to be important in the pathway between cognition and later health. Additional outcome measures will be included in this project as they may provide insights into specific aspects of neurodevelopment that may be particularly sensitive to maternal dietary influences in-utero. The secondary outcomes are:
* Wechsler Objective Reading Dimensions (WORD) test and the Wechsler Objective Language Dimension (WOLD) Test - which measure reading and language respectively,
* Social Communication Disorders Checklist (SCDC), - measures social interaction and communication skills.
* Development and Well-Being Assessment (DAWBA) and the Strengths and Difficulties Questionaire (SDQ) - both designed to measure conduct problems, emotional behaviour and hyperactivity,
* School and hospital diagnosed learning difficulties - will pick up individuals with clinically diagnosed conditions.
* SATS test scores and GCSE results are included in the list of outcomes to determine whether dietary effects on cognition, are translated into school performance. We would only explore associations with this outcome where there was a positive association of a maternal dietary factor with cognitive ability. Thus, this would extend the primary analysis to provide an indication of whether the effect of maternal diet on cognition had an important effect on performance.
* Head circumference- this is a more crude measure of brain development than the other outcome measures proposed in this grant. However, it was measured at birth for all children in the ALSPAC study and as this is an indicator which relates specifically to in-utero development.
The large number of tests generated by having several outcomes will increase the possibility of false positive results. In order to guard against this we will:
* Undertake secondary analyses only when there is an indication to do so from the primary analyses (e.g. with school performance)
* Seek to replicate any positive results (with primary or secondary outcomes) in other cohort studies as described in the proposal.
B388 - The Safety and Efficacy of Raspberry Leaf Herb in Pregnancy An Observational Study nested within the Avon Longitudinal Study of Parents and Children ALSPAC - 07/08/2006
(No outline received).
B381 - An investigation into the relationship between Charles de Coti Marshs teaching and the use of complementary medicine products supplements and dietary habits of children and parents within the Avon Longitudinal Study of P - 10/07/2006
The Arthritic Association is built upon the clear recommendations of Charles de Coti-Marsh for the use of diet, supplements and lifestyle for the amelioration of the symptoms of arthritis. The Home Treatment Programme includes recommendations of a diet of potassium-rich foods andincreased intake of fruit, nuts, vegetables and whole grains, low saturated fat intake, low sugar and salt intake, the use of supplements such as homeopathic Arnica, 'K' compound and Oil of Garlic and the advocation of a lifestyle that includes regular gentle exercise and adequate sleep.
However, as pointed out by the Association there is no evidence yet as to whether the use of such diets and/or treatments may prevent symptoms of arthritis and/or limb and other pain from actually occurring. We propose to use data collected in ALSPAC to assess whether there is any evidence to support such a hypothesis and also to investigate associations between the recommendations of the Home Treatment Programme upon ALSPAC parents with arthritis and parents and children with joint pain. In so doing, this investigation has the unique opportunity to examine these key factors by laying down foundations as to the pre-cursors of children developing arthritis in later life.
B385 - Associations in the Diet and Physical Activity Patterns of 11 year old Children Avon Longitudinal Study of Parents and Children - 07/07/2006
(No outline received).
B382 - Deanfield Programme Renewal - 04/07/2006
(No outline received).
B379 - Does Impaired Autobiographical Memory Mediate Associations between Traumatic Life Events in Childhood and Subsequent Depression and Self-harm - 30/06/2006
The aim of this study is to investigate the association between childhood depression, adversity and abuse, deficits in autobiographical memory measured at 13 years, and the subsequent emergence of new onsets of major depression and self-harm by 15 years.
B378 - Long Term Effects of Bedsharing by Mothers and Infants - 26/06/2006
Mother-baby bedsharing is associated with an increased risk of unexpected infant death, particularly for mothers who smoke or drink alcohol, but little is known of the potential beneficial effects of bedsharing (e.g. establishment or maintenance of breastfeeding), and recent US data has confirmed the beneficial effects of breastfeeding in reducing infant mortality. The Avon Longitudinal Study of Parents And Children (ALSPAC) has collected information on health, growth, development, medical, environmental and social factors from pregnancy to the present, in a cohort of 14,000 children born in 1991-2 and their families. Detailed information has been collected on sleep patterns, duration and place for the infants and their parents. Preliminary analysis of the data on sleep in infancy and childhood has shown that in the first 6 months 33-70% infants share a bedroom with their mother, and routine mother-baby bedsharing for night time sleep is common throughout infancy and early childhood, varying between 9% and 18%. Many factors (e.g. birthweight, breastfeeding), are associated with sleep patterns and duration, and, whilst short sleep duration in early infancy is associated with obesity in later childhood, breastfeeding (which is associated with bedsharing) may reduce the risk of obesity.
We will use complex statistical modelling techniques to analyse the data from ALSPAC children and families, to identify factors contributing to parents choices about bedsharing in infancy, together with any immediate or long term adverse consequences or benefits of bedsharing, room sharing or separate sleeping, for both children and mothers. The large size and completeness of the data from the ALSPAC cohort will allow us to take account of multiple psychological, medical, social and environmental factors that may have influenced decisions about infant care practices, and may themselves have been associated with potential benefits or adverse consequences (e.g. breastfeeding, maternal smoking, socio-economic deprivation, pacifier use).
B376 - Preventable Hearing Loss What is the Prevalence Penetrance and Phenotype of the Mitochondrial A1555G Mutation associated with Aminoglycoside-induced Hearing Loss - 25/06/2006
As suspected the prevalence of the m.1555Agreater than G mutation in the ALSPAC cohort was 1 in 540. This prevalence has potentially important implications for the use of aminoglycoside antibiotics in the UK. For this reason we wish to use the mothers of the ALSPAC children to validate the accuracy of the genotyping results.
Genotyping of both mothers and children provides internal quality control because this is a mitochondrial variant which is homoplasmic. So, any children who are positive for the mutation will have mothers who are postitive, and any children who are negative should not have a mother who is also negative.
B399 - Birth Weight and Interleukin-1 Receptor Antagonist - 21/06/2006
Aims
- To use SNPs in linkage disequilibrium with IL-1RN*2 to genotype the 'Children in Focus' (CIF) cohort of the ALSPAC study.
- To test for association of the inferred IL-1RN*2 genotype with birth weight.
B393 - Dyslexia Genotypes - 16/06/2006
(No outline received).
B375 - Sleep Stress and Mental Health - 16/06/2006
(No outline received).