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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B556 - Relation of adverse psychosocial enviroment to childhood obesity and early puberty as markers of future breast cancer risk - 19/09/2007

B number: 
B556
Principal applicant name: 
Dejana Braithwaite (University of California, USA)
Co-applicants: 
Dr Ken Ong (University of Cambridge, UK), Dr Robert Hiatt (University of California, USA), Dr Pauline Emmett (University of Bristol, UK)
Title of project: 
Relation of adverse psychosocial enviroment to childhood obesity and early puberty, as markers of future breast cancer risk
Proposal summary: 

Objectives/aims:

  1. To establish whether markers of adverse psychosocial environment (such as adverse socioeconomic circumstances and stressful life events) are associated with biochemical markers of cortisol metabolism (fasting cortisol levels and urinary excretion of total cortisol metabolites at age 8), central fat patterning (by waist circumference and DXA), and earlier timing of thelarche and menarche (by questionnaire).
  2. To establish whether these associations are modified by level of physical activity and energy intake.

In addition to providing a test of our proposed stress-body fat-puberty model, the proposed study also has the potential to inform the scientific basis of targeted interventions to reverse the childhood obesity epidemic .

Date proposal received: 
Wednesday, 19 September, 2007
Date proposal approved: 
Wednesday, 19 September, 2007
Keywords: 
Diet, Eating disorders
Primary keyword: 

B552 - Meta-analyses of genetic association studies of psychiatric disorders - 17/09/2007

B number: 
B552
Principal applicant name: 
Prof Marcus Munafo (University of Bristol, UK)
Co-applicants: 
Title of project: 
Meta-analyses of genetic association studies of psychiatric disorders
Proposal summary: 

No outline received

Date proposal received: 
Monday, 17 September, 2007
Date proposal approved: 
Monday, 17 September, 2007
Keywords: 
Genetics
Primary keyword: 

B514 - Association between common variants in the adiponectin gene APM1 or ADIPOQ and childhood growth body composition adiponectin levels and insulin sensitivity - 15/09/2007

B number: 
B514
Principal applicant name: 
Ken Ong (University of Cambridge, UK)
Co-applicants: 
Title of project: 
Association between common variants in the adiponectin gene (APM1 or ADIPOQ) and childhood growth, body composition, adiponectin levels and insulin sensitivity"
Proposal summary: 

No outline received

Date proposal received: 
Saturday, 15 September, 2007
Date proposal approved: 
Saturday, 15 September, 2007
Keywords: 
Endocrine, Genetics, Growth, Weight, Obesiy
Primary keyword: 

B554 - Sexually transmitted infections and sexual behavior in an adolescent cohort - 14/09/2007

B number: 
B554
Principal applicant name: 
Dr Caroline Trotter (University of Bristol, UK)
Co-applicants: 
Prof Matt Hickman (University of Bristol, UK), Prof Jonathan Sterne (University of Bristol, UK), Prof John Macleod (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK), Dr Paddy Horner (University of Bristol, UK)
Title of project: 
Sexually transmitted infections and sexual behavior in an adolescent cohort
Proposal summary: 

Sexual health is an important component of physical and mental health. In the UK, rates of teenage pregnancy are among the highest in western Europe and sexually transmitted infections (STIs) such as chlamydia are common in teenagers and young adults. Sexual behaviour is a normal part of human development and it is crucial to understand the factors that influence sexual health and behaviour through this development process in adolescence to guide suitable public health interventions to improve sexual health.

The ALSPAC cohort is representative and extremely well characterised from before birth. The ALSPAC children are now teenagers, and this offers a unique opportunity to study adolescent sexual behaviour and adverse sexual health outcomes, including sexually transmitted infections. Sexual activity has been measured at age 11, 12, 13+, 15+ and factors affecting relationships between the individual and his/her environment have been measured across the life-course. We propose to repeat the sexual activity questionnaire at the age 17+ clinics and in addition, collect biological samples to test for current and past chlamydia and human papillomavirus (HPV) infection. These infections are common and important in terms of public health policy given the recent introduction of the National Chlamydia Screening Programme and imminent HPV vaccine introduction. Using this data, we will describe the sexual behaviour and prevalence and incidence of chlamdyia and HPV in teenagers, and identify risk factors for adverse sexual health outcomes. By doing so, we aim to identify potentially modifiable behaviours/ factors that can be used to develop sexual health interventions for young people.

Aims:

- To describe the sexual behaviour of ALSPAC participants attending the age 17+ clinics

- To establish the prevalence of current and past infection with chlamydia in ALSPAC participants attending the age 17+ clinics

- To establish the prevalence of current and past infection with HPV in ALSPAC participants attending the age 17+ clinics

- To measure associations between sexually transmitted infections with current and past sexual behaviour and other risk taking behaviours

- To establish early-life influences and predictors of adverse sexual health outcomes

Methods:

We propose to engage the cohort in the next round of clinics at age 17+ years. Participants attending the clinics will be invited to complete a computer assisted self-interview (CASI) on 'romantic relations' and other relevant risk behaviours, particularly substance use. The romantic relations questionnaire was first introduced at the age 11+ clinic and to maintain consistency between assessments we will retain this questionnaire. However, we will also assess whether further questions should be added, for example, to allow direct comparisons with NATSAL. Participants will be invited to give blood and first catch urine samples which will be used to test for active and past infection with chlamydia and HPV (see below). In addition, informed consent will also be sought to test stored samples collected in the age 15+ and 13+ clinics.

These data will be analysed to describe the age-specific sexual behaviour and the incidence and prevalence of HPV and chlamydia. We will then identify risk factors for HPV and/or chlamydia infection over life course and associations with other risk taking behaviours. Predictor variables from biological, individual, family, peer, social and cultural domains will be considered for inclusion in regression models.

Date proposal received: 
Friday, 14 September, 2007
Date proposal approved: 
Friday, 14 September, 2007
Keywords: 
Primary keyword: 

B490 - Determination of FT1 abundance in ALSPAC sample lysate - 14/09/2007

B number: 
B490
Principal applicant name: 
Prof George Davey Smith (University of Bristol, UK)
Co-applicants: 
Prof Jeff Holly (University of Bristol, UK), Nick Timpson (University of Bristol, UK)
Title of project: 
Determination of FT1 abundance in ALSPAC sample lysate.
Proposal summary: 

Project outline:

The recent swathe of genomewide analyses, which are essentially acephalous scientific experiments testing all available genetic variants for association with common disease traits, has thrown up a series of apparently novel pathways for further analysis. One of these is that of the FTO locus of chromosome 16 which has been shown now to have a association with T2D driven entirely by its robust associaion with fat mass (Zeginni et al Science 2007, Frayling et al Science 2007). As yet, neither the driving force behind this association, nor its biological foundation have been elucidated.

Returning to the work of Remy & Michnick (Molecular and Cellular Biology) and personal experience alongside Pof Jeremy Tavare, Prof Holly recalled that the adjacent locus to FTO, AKTIP (seen below)fundamentally involved in the insulin signalling pathway. This protein has been observed to enhance the PKB mediated recruitment of GLUT4 to the cell surface and hence the action of IGF1, IGF2, and consequent responsiveness to insulin.

Whilst not the actual site of association

Observed by Zeginni and Frayling, the

protein (FT1) encoded by AKTIP

may well lie in the 5' promoter of the

FTO locus, possibly having an impact on

the expression pattern and profile of the

locus concentrated on by these new

reports.

In efforts to verify this, a simple

experiment can be performed which can

enable one to assess the relative

abundance of this protein (FT1) in the

lysate of spent samples (here derived from

the ALSPAC cohort. With genotypes

already collected for this cohort, one simply

requires samples of cell pellets for examination via the use of FT1 antibody which has already been developed and delivered to Bristol (and lab in question here) by Remy and Michnick. This experiment will employ simple western blotting approaches for the examination of FT1 protein levels (measured in a semi-quantitative manner) in individuals organised by their respective FTO genotype. Under the hypothesis that the FTO locus is exerting its observed metabolic association through its interaction with the FT1 locus, one may anticipate a genotype specific difference in the yield of FT1 by this approach.

Date proposal received: 
Friday, 14 September, 2007
Date proposal approved: 
Friday, 14 September, 2007
Keywords: 
Primary keyword: 

B551 - Early origins of coronary heart disease Application of the Illumina50k chip to the Avon Longitudinal Study of Parents and Children - 14/09/2007

B number: 
B551
Principal applicant name: 
Prof George Davey Smith (University of Bristol, UK)
Co-applicants: 
Title of project: 
Early origins of coronary heart disease: Application of the Illumina50k chip to the Avon Longitudinal Study of Parents and Children
Proposal summary: 

No outline received

Date proposal received: 
Friday, 14 September, 2007
Date proposal approved: 
Friday, 14 September, 2007
Keywords: 
Genetics
Primary keyword: 

B550 - NIH Mercury - 13/09/2007

B number: 
B550
Principal applicant name: 
(Not used 0, Not used 0)
Co-applicants: 
Dr Philippe Grandjean (Harvard School of Public Health, USA)
Title of project: 
NIH Mercury
Proposal summary: 

Fish and seafood are regarded healthy components of a varied diet, particularly important for pregnant women so that they can pass on essential nutrients needed for fetal development of the brain and other organs1. On the other hand, fish may contain environmental pollutants, such as methylmercury, that can put fetal brain development at risk2. A balance has been sought by state and federal agencies in advising the public 3, but certain subpopulations (i.e. pregnant women or women of childbearing age) generally eat less fish than desirable in order to obtain the beneficial effects of fish 1. At the same time, U.S.EPA reports that over 300,000 children born every year exceed the Reference Dose (RfD) for methylmercury and may therefore be at risk at developing adverse effects4.

Tragic pollution episodes have clearly documented that the fetal brain is particularly susceptible to methylmercury toxicity; the adverse effects on the nervous system appear to be irreversible and are much more widespread and serious in children than in adults, especially when exposures have occurred prenatally5,6. While the existence of adverse effects at low exposure levels has been affirmed by national and international regulatory agencies,7-10 certain scientific questions remain unanswered. They relate to the possible occurrence of neurotoxic effects close to the U.S.EPA Reference Dose, the persistence of the cognitive deficits through adolescence, and the possible compensation of adverse effects by essential nutrients present in fish and seafood. The proposed research aims at developing new and more definite information on the benefits and risks associated with seafood intakes at levels relevant to the US general population.

This proposal builds upon the extensive data already collected on a cohort of 14,138 children born between April 1st 1991 and December 31st 1992 in Avon, England, as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) study11. The focus was to identify features of the environment that affect the health and development of children. Detailed information and biological samples were collected at the time of birth and continue to be collected during the course of follow-up11. A10% sample randomly selected was seen at 4, 8 and every 6 months until age 5 years with data including motor and intellectual development. From age 7 years, all children were invited annually for neurobehavioral assessment (including IQ). A pilot project was carried out to measure cord-mercury wet-weight concentrations12, and frozen cords are available from 7,500 subjects to link to the outcome parameters already available.

Because cord tissue has been collected from over half of the children, and because the mercury concentration in the umbilical cord is an excellent biomarker of prenatal exposure levels13, the opportunity exists to assess the developmental mercury exposure level to determine its possible impact on highly relevant neurodevelopmental functions, and the possible interaction with beneficial effects of maternal fish intake.

The specific aims of this project are therefore: to determine if methylmercury-associated cognitive deficits are present at low-level prenatal methylmercury exposures and remain detectable through to adolescence;

  • to examine whether intake of fish containing beneficial nutrients affect the same outcomes and counterbalance the methylmercury-associated deficits; and
  • to identify other behavioral outcomes that are linked to prenatal methylmercury exposure for possible consideration in future research.
Date proposal received: 
Thursday, 13 September, 2007
Date proposal approved: 
Thursday, 13 September, 2007
Keywords: 
Genetics
Primary keyword: 

B553 - FAVOUR Fruit and Vegetables for our children FP7 - 11/09/2007

B number: 
B553
Principal applicant name: 
Dr Pauline Emmett (University of Bristol, UK)
Co-applicants: 
Alison Stephen (MRC Human Nutrition Research, UK), Dr Kate Northstone (University of Bristol, UK), Mrs Louise R Jones (University of Bristol, UK)
Title of project: 
FAVOUR Fruit and Vegetables for our children FP7
Proposal summary: 

FAVOUR work package 4

Epidemiological investigations of impact of fruit and vegetables introductions at weaning on subsequent intake

Data analysis of existing longitudinal studies - ALSPAC, DONALD

Objectives Statistical analysis of fruit and vegetable eating in childhood in relation to early introduction of fruit and vegetables

Exploration of the relationship of socio-economic background to early feeding and later intake of fruit and vegetables

Description of work

ALSPAC: The Avon Longitudinal Study of Parents and Children (ALSPAC) was devised specifically to determine the ways in which the environment influences the health and development of the child (Golding et al,2001; http://www.alspac.bris.ac.uk/). Detailed information was collected regarding weaning practice and records of the child's food/drink intake were kept at repeated time points. During infancy, mothers completed questionnaires covering the age of introduction and types of weaning and family foods given to the child (at ages 6 and 15 months). Frequency of intake of fruit and vegetables was assessed by questionnaire at age 7 years. Preliminary analysis of this data has shown that children introduced to raw and home-cooked fruit and vegetables by 6 months of age ate fruit and vegetables more often at age 7 years than did those introduced to ready-prepared foods. More detailed food and drink record data were collected using 3d unweighed diaries from 750 to 1000 of the children at 4, 8, 18 months, 3.5, 5, 7 and 10 years. A complete range of foods and drinks consumed at each age is available as well as socio-economic background.

DONALD: The DONALD study is an ongoing open cohort study with about 40 new infants recruited every year. Currently there are 750 children and adolescents taking part. Dietary assessment has been conducted in the DONALD study as 3d weighed dietary records at ages 3, 6, 9, 12, 18, 24, 36 months. Food consumption is broken down to single food items including those from composite foods such as baby jars, and it is possible to distinguish between home prepared meals and commercial products at each age.For both studies, the diet records have been coded and analysed and information about food/drink and nutrient intakes including details of actual fruits and vegetables eaten is available. Children will be grouped according to fruit and vegetable weaning practice. Intakes of fruits, vegetables and other foods at each age up to 10 years will be investigated to determine the likely influence of these weaning behaviours. The socio-economic position of the families will be taken into consideration to determine the influence of these external factors on weaning practice. At each of the two cohorts a research nutritionist will be employed to carry out this work. The work will complement the results of the intervention study in work package 3.

Task 4.1 Assembly of dietary dataset covering weaning and later childhood diet Incorporate data from diet records from various timepoints covering nutrients and foods/drinks consumed. Create groups of subjects according to their fruit and vegetable weaning practice at 6 months.

Task 4.2. Linking of dietary dataset to socio-economic background variables. Compile socio-economic background data including educational level and age of mother, housing tenure, marital status and incorporate into dietary dataset

Task 4.3. Establishment of protocol for statistical analysis. Provide descriptive statistics of fruit and vegetable intakes at various ages and discuss with partners to establish protocol for the statistical analysis

Task 4.4. Statistical analysis. Determine amount of fruit eaten at each age in relation to eating raw fruit, home cooked, and ready-prepared fruit. Determine amount of vegetables at each age in relation to eating raw vegetables, home-cooked vegetables, and ready-prepared vegetables by 6 months.Investigate differences in nutrient intakes at each age according to type of fruit and vegetables introduced by 6 monthsInvestigate differences in other food/drinks consumed at each age according to type of fruit and vegetables introduced by 6 months

Task 4.5 Adjustment for socio-economic influences. Investigate the influence of socio-economic position on fruit and of vegetable eating at each age in relation to weaning practice.

Date proposal received: 
Tuesday, 11 September, 2007
Date proposal approved: 
Tuesday, 11 September, 2007
Keywords: 
Diet, Eating disorders
Primary keyword: 

B548 - Outcomes of moderately premature infants born at 33-36 weeks of gestation - 10/09/2007

B number: 
B548
Principal applicant name: 
E Boyle (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Outcomes of moderately premature infants born at 33-36 weeks of gestation
Proposal summary: 

No outline received

Date proposal received: 
Monday, 10 September, 2007
Date proposal approved: 
Monday, 10 September, 2007
Keywords: 
ADHD, Antisocial Behaviour, Behavioural Problems
Primary keyword: 

B549 - Birthweight and subsquent levels of glucose and insulin a quantitative systematic review of published evidence - 06/09/2007

B number: 
B549
Principal applicant name: 
Prof Peter Whincup (St Georges University, London, UK)
Co-applicants: 
Miss S Kaye (Not used 0, Not used 0), Prof Derek Cook (Not used 0, Not used 0), Dr Charlie Owen (Not used 0, Not used 0)
Title of project: 
Birthweight and subsquent levels of glucose and insulin: a quantitative systematic review of published evidence
Proposal summary: 

Background:

Early life exposures have been hypothesised to affect subsequent levels of glucose and insulin. We aim to draw together all of the research done to date looking at this possible relationship in all normal populations in both children and adults.

Scientific hypothesis:

That there is an association between birthweight and subsequent levels of glucose and insulin.

Objectives:

To establish the difference in mean levels of fasting and post load glucose and insulin per one Kg increase in birthweight. We also wish to examine the effect of potential modifiers and confounders.

Methodology and planned statistical analyses:

The first stage is to identify all studies with published reports on the relationship between birthweight and subsequent levels of glucose and insulin in general populations of both children and adults. Investigators will be asked to provide data (preferably) or to carry out pre-defined analyses. Individual study data will be analysed with multiple logistic regression to obtain estimates for the differences in glucose and insulin that are associated with a 1 kg increase in birthweight, based on the full range of birthweights for each study. Models will be fitted without adjustment and then with additional adjustments for

* age and (if appropriate) gender

* for social class

* current body mass index

Analyses will also examine the effect of excluding subjects with

* birthweights greater than 4kg

* maternal diabetes.

The estimates will then be included in meta-analyses, carried out using fixed-effects modelling if there is not appreciable evidence of heterogeneity.

Date proposal received: 
Thursday, 6 September, 2007
Date proposal approved: 
Thursday, 6 September, 2007
Keywords: 
Weight
Primary keyword: 

B544 - The lifecourse determinants of oral health in a contemporary birth cohort - 31/08/2007

B number: 
B544
Principal applicant name: 
D Jagger (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
The lifecourse determinants of oral health in a contemporary birth cohort
Proposal summary: 

No outline received

Date proposal received: 
Friday, 31 August, 2007
Date proposal approved: 
Friday, 31 August, 2007
Keywords: 
Primary keyword: 

B542 - A study of psychosis-like symptoms PLIKS in 17-year old adolescents in ALSPAC - 30/08/2007

B number: 
B542
Principal applicant name: 
Prof Mary Zanarini (Harvard School of Public Health, USA)
Co-applicants: 
Dr Stanley Zammit (University of Cardiff, UK), Prof Chris Hollis (Not used 0, Not used 0), Prof Glyn Lewis (University of Bristol, UK), Prof Glynn Harrison (University of Bristol, UK), Prof Peter Jones (University of Cambridge, UK), Prof Dieter Wolke (University of Warwick, UK), Prof David Gunnell (University of Bristol, UK)
Title of project: 
A study of psychosis-like symptoms (PLIKS) in 17-year old adolescents in ALSPAC
Proposal summary: 

AIMS The aim of this proposal is to examine risk factors for developing psychosis-like symptoms (PLIKS) during late adolescence within a population-based birth cohort. Furthermore, we will examine factors affecting persistence of PLIKS throughout adolescence, and the pathways from developing PLIKS in early adolescence through to disorder (PLIKS with concurrent functional impairment) in late adolescence, focusing on both risk and protective factors that are likely to be operating along this trajectory. More specifically, the aims of this proposal are:

1) To carry out an interview-based assessment of PLIKS, along with measures of functional impairment, in order to determine the prevalence and distribution of sub-clinical PLIKS, and of PLIKS related disorder (PLIKS and concurrent functional impairment) in 17-year olds.

2) To investigate whether established risk factors for adult onset psychotic illness (maternal exposures during pregnancy, pregnancy and birth complications, social relationships during childhood and adolescence, social cognition, emotional experiences, cognitive ability, substance use, and genetic variation) alter risk of developing PLIKS at age 17, or impact upon persistence of symptoms (from assessment at age 12 through to age 17 assessment) or transition into PLIKS related disorder.

3) To further refine and increase the validity and positive predictive value of a self-rated questionnaire-based assessment of PLIKS by comparing self-reported responses to structured questions with observer ratings of PLIKS from a semi-structured interview

Date proposal received: 
Thursday, 30 August, 2007
Date proposal approved: 
Thursday, 30 August, 2007
Keywords: 
Depression, Mental Health
Primary keyword: 

B541 - Role of PHLDA2 in fetal growth - 29/08/2007

B number: 
B541
Principal applicant name: 
Prof Gudrun Moore (UCL Institute of Child Health, London, UK)
Co-applicants: 
Mr David Monk (Not used 0, Not used 0)
Title of project: 
Role of PHLDA2 in fetal growth
Proposal summary: 

The Objective

Understanding the basic molecular mechanisms for growth in utero will eventually lead to prevention or therapy for intrauterine growth restriction (IUGR). Our group and others have shown that imprinted genes have an important role in fetal growth both in mouse and man (1). Some of these genes are imprinted in the placenta and their role appears to be linked to successful nutrient transfer, which is vital for normal fetal growth (2). The objective of this proposal is to follow up our study on the maternally expressed PHLDA2 imprinted gene and its promoter region. The expression of PHLDA2 in the placenta has been negatively correlated with growth (3). Recently we have found a deletion polymorphism in the PHLDA2 promoter region that exhibits a trend implicating a role in its growth suppressing function.

Date proposal received: 
Wednesday, 29 August, 2007
Date proposal approved: 
Wednesday, 29 August, 2007
Keywords: 
Genetics
Primary keyword: 

B545 - Prediction of Drinking Outcomes in ALSPAC An Update - 28/08/2007

B number: 
B545
Principal applicant name: 
Prof Marc Schuckit (University of California, San Diego, USA)
Co-applicants: 
Title of project: 
Prediction of Drinking Outcomes in ALSPAC: An Update
Proposal summary: 

?SEQ CHAPTER h
1Our overall goal is to add a limited number of additional variables to our current data analyses using the ALSPAC data. We currently have information on the level of response to alcohol and demography at age 12-13, know the outcome regarding a limited number of alcohol-related variables at age 14-15, and have models of how the level of response to alcohol relates to alcoholic outcomes in teenagers and adults from several additional studies (the Collaborative Study on Genetics of Alcoholism, the San Diego Prospective Study adults, and the San Diego Prospective Study adolescents). However, to date none of these structural equation models have been tested in subjects in their early teens. Therefore, if several additional areas of data can be made available to us within the next week or so, we will be able to test whether aspects of the structural equation models generated in late teenagers and adults apply to the ALSPAC population using predictors from age 12-13. The published structural equation models have utilized both the MPlus approach and the AMOS programs as described in the references offered below. To carry out these analyses, we would be grateful for any of the following variables as an update to the data already supplied to us in June 2007.

Date proposal received: 
Tuesday, 28 August, 2007
Date proposal approved: 
Tuesday, 28 August, 2007
Keywords: 
Alcohol, Drugs
Primary keyword: 

B536 - When to have another baby An event history analysis of the reproductive decisions of contemporary British mothers MERGED WITH B535 - 20/08/2007

B number: 
B536
Principal applicant name: 
Prof Ruth Mace (University College London, UK)
Co-applicants: 
Mr David Lawson (University College London, UK)
Title of project: 
When to have another baby? An event history analysis of the reproductive decisions of contemporary British mothers. (MERGED WITH B535)
Proposal summary: 

Aim:

Using existing ALSPAC data this project will model social, economic and demographic measures as risk factors for having another baby over the following decade. ALSPAC provides an unusually detailed dataset to consider these questions, providing regular time varying data on a range of relevant variables. Accordingly, multilevel event history models will be utilised to gain a uniquely sophisticated longitudinal analysis of the determinants of fertility. The project aims to appraise current theories of reproductive decision making grounded in evolutionary and economic theories of fertility (e.g. Kaplan et al., 2002; Mace, 2007) and further promote integration between these two frameworks.

Date proposal received: 
Monday, 20 August, 2007
Date proposal approved: 
Monday, 20 August, 2007
Keywords: 
Social Science, Stress, Social Conditions
Primary keyword: 

B535 - Contact with kin childhood development trajectories in contemporary Bristish families MERGED WITH B536 - 20/08/2007

B number: 
B535
Principal applicant name: 
Prof Ruth Mace (University College London, UK)
Co-applicants: 
Title of project: 
Contact with kin & childhood development trajectories in contemporary Bristish families (MERGED WITH B536)
Proposal summary: 

Aims:

Grounded in evolutionary life history theory (Mace and Sear, 2005), the proposed research will examine the wider rearing environment of British children as a determinant of social and physical development trajectories, using the Avon Longitudinal Study of Parents and Children cohort (ALSPAC - children born in 1991/92). A previous study on this cohort has already identified a distinction in the impact of informal friend or kin-based care vs. paid care in determining cognitive outcomes by age 7 (Gregg et al., 2005) The proposed research takes a broader focus considering a wider range of development outcomes, over a longer period, and crucially will involve a more precise categorisation of contact with kin and investments by kin, informed by evolutionary demography. Outcome variables will include childhood malaise, growth, cognitive development and pubertal timing. ALSPAC provides an unusually detailed dataset to consider these questions, providing regular time-varying data on a wide range of relevant variables. Accordingly, multivariate multilevel models for change (Singer and Willet, 2003) will be utilised to gain a uniquely sophisticated longitudinal analysis of the role of contact with kin in childhood well-being.

Date proposal received: 
Monday, 20 August, 2007
Date proposal approved: 
Monday, 20 August, 2007
Keywords: 
Social Science, Stress, Social Conditions
Primary keyword: 

B538 - Effects of BDNF and ACE genes on normal variation in cognitive function - 14/08/2007

B number: 
B538
Principal applicant name: 
(Not used 0, Not used 0)
Co-applicants: 
Prof Peter Jones (University of Cambridge, UK), Jennifer Barnett (Not used 0, Not used 0)
Title of project: 
Effects of BDNF and ACE genes on normal variation in cognitive function
Proposal summary: 

The project would be two genetic association studies assessing the effects of variations in two genes (BDNF and ACE) on normal variation in cognitive function in ALSPAC. This would be an extension of our previous, successful collaboration in which we have investigated the effects of SNPs in the COMT, 5HTTP and MAOA genes (Barnett et al 2007). Analyses are hypothesis-driven (see below). Outcome measures would be cognitive scores from ages 8 (attention and IQ) and ten years (working memory). Genotype data would be required for the ACE and BDNF genes, which we understand has already been completed in the cohort.

Brain-derived neurotrophic factor (BDNF) is one of the group of neurotrophins which affect cell survival, axonal and dendritic growth and synaptic plasticity among dopaminergic and other neurons (Bath and Lee 2006). The BDNF gene on 11p13 contains a common Val-Met substitution at codon 66. The Met allele is associated with smaller hippocampal volume (Pezawas et al 2004; Szeszko et al 2005) and better memory (Egan et al 2003; Hariri et al 2003; Dempster et al 2005; Tan et al 2005; Ho et al 2006) but not attention, processing speed, language or planning abilities (Ho et al 2006). The relative rarity of Met/Met homozygotes (about 4% of the US population, (Shimizu et al 2004)) means that the cognitive status of Met/Met individuals is effectively unknown. There have been no studies, to our knowledge, of the effect of BDNF genotype on children's cognitive function, despite the obvious importance of BDNF in neurodevelopment.

Angiotension-converting enzyme (ACE) is a central enzyme of the renin-angiotensin system (RAS) and is primarily involved in blood pressure regulation. It is widely distributed throughout the brain, and particularly associated with cerebral blood vessels, and astrocytes of the periventricular nuclei. Raised RAS activity through elevated ACE is thought to impair cellular metabolism (Williams et al 2000) and amplify free radical and pro-inflammatory responses (Harding et al 2005). ACE may therefore play a role in neurodevelopmental progress and subsequent cognitive development (Harding et al 2005) as well as late-life cognitive decline (Amouyel et al 1996). This hypothesis is supported by demonstrations that ACE inhibitors improve cognitive function (Amenta et al 2002; Tzourio et al 2003).

The ACE gene on 17p23 contains a 287bp insertion/deletion polymorphism in intron 16. Both tissue and circulating ACE levels are higher in individuals with two copies of the deletion allele (Tiret et al 1992). The insertion allele appears to confer a slightly increased risk for Alzheimer's disease (Narain et al 2000) while the deletion allele has been repeatedly associated with increased risk for age-related cognitive impairment and dementia (Amouyel et al 1996; Palumbo et al 1999; Bartres-Faz et al 2000; Richard et al 2000; Stewart et al 2004). Deletion allele carriers are reported to show greater cognitive impairment in moderate and severe traumatic brain injury (Ariza et al 2006), less improvement after shunt surgery in normal pressure hydrocephalus (del Mar Matarin et al 2005), and reduced cognitive impairment in alcoholism (Bartres-Faz et al 2002). However three epidemiological studies have found no associations between ACE genotype and normal cognitive ageing (Visscher et al 2003, Frederiksen et al 2003, Yip et al 2002). Two studies have investigated the effects of ACE genotype on cognitive function in children (Gao et al 2006, Harding et al 2005). Both studies were negative, however both were limited by sample size and by the relatively crude cognitive measure they employed.

Date proposal received: 
Tuesday, 14 August, 2007
Date proposal approved: 
Tuesday, 14 August, 2007
Keywords: 
Endocrine, Obesity, Weight, Genetics
Primary keyword: 

B537 - HOPE Project - 14/08/2007

B number: 
B537
Principal applicant name: 
Dr Adriano Cattaneo (Institute for Child Health Burlo Garofolo, Europe)
Co-applicants: 
Dr David Batty (University of Glasgow, UK)
Title of project: 
HOPE Project
Proposal summary: 

HOPE Project (http://www.hopeproject.eu/)

Work Package 3 (WP3): Early Childhood Obesity Prevention.

Objectives:

1. To describe differences in prevalence and trends in overweight and obesity across Europe in infants and preschool children.

2. To identify specific obesogenic nutrition and physical activity patterns in infants and preschool children across Europe.

3. To identify family-environmental determinants of overweight and obesity including types of feeding, weaning practices, optimum activity learning techniques in infants and preschool children across Europe.

4. To produce a checklist for good quality interventions, as a means of strengthening the evidence base regarding effectiveness of interventions.

Date proposal received: 
Tuesday, 14 August, 2007
Date proposal approved: 
Tuesday, 14 August, 2007
Keywords: 
Endocrine, Weight, Obesiy
Primary keyword: 

B543 - The communicating teenagerInvestigating the role of language and literacy in the employability and social success of the young people of ALSPAC - 10/08/2007

B number: 
B543
Principal applicant name: 
Prof Susan Roulstone (University of the West of England (UWE), Bristol)
Co-applicants: 
Dr Jane Powell (University of the West of England (UWE), Bristol), Dr Judy Clegg (University of Sheffield, UK), Prof Timothy James Peters (University of Bristol, UK), (Queen Margaret University, UK), Prof Alan Emond (University of Bristol, UK), Miss Laura Miller (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK)
Title of project: 
The communicating teenager.Investigating the role of language and literacy in the employability and social success of the young people of ALSPAC
Proposal summary: 

The overall aim is to investigate the role that language and literacy play in the educational and social functioning of young people as they enter adulthood and to identify factors and processes that are associated with positive and negative outcomes. Four work streams will focus on particular objectives as follows: 1. To identify risk and protective factors associated with language and literacy outcomes. In particular we will identify: how speech, language, literacy and cognitive variables cluster and change during childhood; to what extent do language learning and literacy difficulties persist to school leaving age predictors of language and literacy performance at school leaving age; mechanisms and characteristics by which social class impacts upon children's language and literacy during preschool, primary school and at school leaving. 2. To identify the relationship between young people's current and past performance in language and literacy and their decisions about social activities, further education and future employment as they leave school. We aim to identify the patterns of social, educational and employment outcomes at school leaving age that are related to different language learning and literacy trajectories; social conditions that predict young people's perceptions of their own functional language and literacy performance and outcomes. 3. To identify the prevalence of conduct and behaviour disorders, risk taking and criminal offending behaviours in relation to young people's current and past performance in language and literacy. In particular we will identify any subgroups of speech, language and literacy deficits that are associated with raised occurrence of psychopathology and /or conduct disorders and at what age the mental health impact become apparent. 4. To identify the current and predicted social costs and return on investment to society as a whole from support of children's language and literacy skills development through professional involvement of speech and language services. Particular objectives include: What is the relationship between GCSE performance outcomes and the level of support in childhood for language and literacy skills development and how does this translate to economic resource savings in the UK economy? To identify whether children with language and literacy difficulties who have received support in childhood through the professional involvement of speech and language services choose higher skill occupation destinations than who have not received such support and, if so, what are the social costs incurred? To identify the economic benefits in monetary terms of professional involvement in language and literacy skills support for emotionally and socially vulnerable young people. Finally it is also an objective of the project to create an archive of the language samples from 5, 8 and from the young people at 17+.

Date proposal received: 
Friday, 10 August, 2007
Date proposal approved: 
Friday, 10 August, 2007
Keywords: 
Speech & Language
Primary keyword: 

B531 - Combined depression and head injury at 17 - 10/08/2007

B number: 
B531
Principal applicant name: 
Prof Alan Emond (University of Bristol, UK)
Co-applicants: 
Prof Glyn Lewis (University of Bristol, UK), Prof Marcus Munafo (University of Bristol, UK), Kate Button (University of Bristol, UK)
Title of project: 
Combined depression and head injury at 17+
Proposal summary: 
Date proposal received: 
Friday, 10 August, 2007
Date proposal approved: 
Friday, 10 August, 2007
Keywords: 
Depression
Primary keyword: 

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