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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B484 - Physical activity and depression in mothers from a community ALSPAC sample - 24/07/2007

B number: 
B484
Principal applicant name: 
Dr Anne M Haas (University of Bristol, UK)
Co-applicants: 
Dr Melvin Hillsdon (Not used 0, Not used 0), Dr Jonathan Evans (University of Bristol, UK), Dr Jon Heron (University of Bristol, UK)
Title of project: 
Physical activity and depression in mothers from a community (ALSPAC) sample
Proposal summary: 

This study aims to use the ALSPAC data to examine the association between risk of a 'high depressive symptom score' and levels of physical activity during pregnancy. The ALSPAC data is ideally suited to address this question as it has an appropriate measure of exposure, at more than one time point, an outcome measure that has been accepted in previous publications and a longitudinal, prospective design.

Date proposal received: 
Tuesday, 24 July, 2007
Date proposal approved: 
Tuesday, 24 July, 2007
Keywords: 
Primary keyword: 

B522 - Does the FTO genotype interact with dietary energy density in the causation of obesity in children - 17/07/2007

B number: 
B522
Principal applicant name: 
Laura Johnson (Not used 0, Not used 0)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK), Dr Susan Jebb (University of Cambridge, UK), Dr Pauline Emmett (University of Bristol, UK)
Title of project: 
Does the FTO genotype interact with dietary energy density in the causation of obesity in children?
Proposal summary: 

Appetite is tightly controlled by internal physiological mechanisms in younger children but a decline in the degree of innate appetite control is observed with age 1-3. It has been postulated that external factors, such as palatability of food, begin to influence internal controls and ultimately override satiety signals 4. The energy density of food has been shown to increase energy intake and short term weight gain in experimental studies 5. Energy density is closely related to the palatability of a food and may disrupt appetite control by over stimulating sensory centres in the brain, which process information on texture and taste of food. An association between fat mass and the FTO gene has recently been identified 6. No functional information about the FTO gene is currently available. Human tissue panel expression studies showed that the FTO gene was most highly expressed in the brain, specifically the cerebral cortex, which may implicate a role in the sensory centres, located in the prefrontal cortex.

I hypothesise that the relationship between dietary energy density and obesity, which we have shown to vary by age in the ALSPAC sample 7, may also vary by the FTO genotype, such that children carrying the high-risk allele A will have a stronger relationship between energy density and obesity than those without. Since the relationship between the FTO gene and BMI z score also appeared to get stronger with age this may be explained by age related changes in appetite control in response to energy dense foods. So I would hypothesise further that the interaction between FTO and energy density on obesity may also get stronger with age.

Data requirements:

This analysis would require access to existing data at ALSPAC from direct assessment and biological samples including:

  • Dietary energy density from diet diaries at age 10 years
  • Genotype for FTO gene
  • Fat mass from DXA at age 13 years
  • Height measured at age 13 years (In order to adjust fat mass for height)

The proposed work would be split between MRC HNR and ALSPAC. Laura Johnson, at MRC HNR, would generate the dietary energy density variable from the dietary data at age 10 years. This variable would be checked and cleaned by Laura and sent to ALSPAC. Nick Timpson, at ALSPAC, would perform the analysis of association between the FTO genotype, dietary energy density and fat mass. Laura Johnson would then write up the results of the analysis in a paper.

The plan of analysis to test the hypothesis would be to initially inspect the data for potential associations using cross tabs. If there is evidence for an association then a linear regression should be performed with fat mass (adjusted for height) as the dependent variable and the FTO gene, dietary energy density (DED) and FTO*DED interaction term as independent variables.

If there is evidence for an interaction then a linear regression analysis of fat mass and DED stratified by genotype would be done in order to test the hypothesis that the relationship between DED and obesity is stronger in children with the A allele. Further analysis could include a logistic regression with obesity (the top quintile of fat mass adjusted for height) as the dependent variable and the FTO gene, dietary energy density (DED) and FTO*DED interaction term as independent variables. Followed by stratification by genotype if evidence of an interaction is found.

Calculations in Quanto (http://hydra.usc.edu/gxe/) indicate that using a sample of 5000 children there is a power of 0.99 to detect a true positive effect, using the following parameters to estimate power:

For the continuous outcome fat mass index (kg/m5.8);

Risk allele (A) frequency = 0.39

Mode of inheritance = additive

Dietary energy density standard deviation = 1.5 kJ/g

Fat Mass Index mean = 1.21 kg/m5.8, standard deviation = 0.63

Main effect sizes

Gene B = 0.1 kg/m5.8 per A allele

Diet B = 0.05 kg/m5.8 per 1kJ/g

Gene*Diet B = 0.05 to 0.15

N = 5000

Power for all G*E effect sizes between 0.05 and 1.5 was 0.99, meaning that it should be possible to detect an interaction effect as small as 0.05 kg/m5.8

Date proposal received: 
Tuesday, 17 July, 2007
Date proposal approved: 
Tuesday, 17 July, 2007
Keywords: 
Genetics
Primary keyword: 

B527 - Depression at 17 - 17/07/2007

B number: 
B527
Principal applicant name: 
Prof Glyn Lewis (University of Bristol, UK)
Co-applicants: 
Title of project: 
Depression at 17
Proposal summary: 

Depression in adolescence is important for a number of reasons. First, there is a high risk of recurrence in adulthood. Evidence from both clinical1 and community2 studies finds that adolescents with depression are more likely to have depression as adults. For example in Lewinsohn's Oregon study2 45% of 16 year olds with depression had a recurrence before the age of 23 (odds ratio 3.2 compared to no disorder). Second, once a person has had an episode of depression, it seems that future episodes are easier to provoke.3 In other words, successfully preventing the first episode of depression in adolescence might have much greater public health benefit than preventing recurrent episodes in adulthood. Third, adolescence is a critical period of life and can interfere with educational attainment and have detrimental effects on future occupation and the stability of future relationships4. Finally, self-harm is common in young people with depression5 and is associated with a substantial risk of suicide.

We propose to study depression at age 17 years in the Avon Longitudinal Study of Parents and Children (ALSPAC), a large birth cohort based in Bristol. Results from the ONS Longitudinal study suggest that the peak incidence of depression and anxiety occurs in young people6 in contrast to the prevalence that is higher in middle age. Depression has been measured before in ALSPAC, and the last occasion was at 15. However, the rates of depression are increasing rapidly at this age and the current proposal will allow investigation of a number of hypotheses by carrying out an assessment of depression at 17 years. It will also allow us to investigate psychological vulnerability factors for depression.

Date proposal received: 
Tuesday, 17 July, 2007
Date proposal approved: 
Tuesday, 17 July, 2007
Keywords: 
ADHD, Antisocial Behaviour, Behavioural Problems
Primary keyword: 

B521 - Diagnosing Autistic Spectrum Disorders Health and Social Implications - 10/07/2007

B number: 
B521
Principal applicant name: 
Ms Virginia Russell (Egenis, (ESRC Centre for Genomics in Society) , UK)
Co-applicants: 
Title of project: 
Diagnosing Autistic Spectrum Disorders: Health and Social Implications
Proposal summary: 

It has been argued that diagnosis of learning disorders including those associated with ASD involves stigmatisation and is therefore not desirable.1,2, 3 Parents have claimed that the social factors involved in identification, interpretation and remediation determine what it means to be autistic.4 On the other hand many clinicians, health practitioners, educators and parents have argued that ASD is partly genetically determined and diagnosis is essential as young as possible to treat and manage the condition.5,6 In order to address this debate we examine whether diagnosing ASD in children leads to a deterioration or improvement of the condition over time as compared to an undiagnosed group with similar social awareness skills, using ALSPAC data.

How parents perceive diagnosis of ASD at the point of diagnosis has not been studied. To address this, a qualitative study will examine what triggers parents to ask for diagnosis, and how parents, who receive or do not receive a diagnosis, view the diagnosis of the condition and construct their own explanations and causes for it. These views will be mapped on to the views of experts to examine any differences of perspective that may exist to highlight how parents and professionals can best work together to help the children.

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

B525 - Determining the causal effect of vitamin D on perinatal metabolic vascular and bone health - 08/07/2007

B number: 
B525
Principal applicant name: 
Prof Debbie A Lawlor (University of Bristol, UK)
Co-applicants: 
Dr Bill Fraser (University of Liverpool, UK), Prof Naveed Sattar (University of Glasgow, UK), Dr Tom Gaunt (University of Bristol, UK), Dr Dave Evans (University of Bristol, UK)
Title of project: 
Determining the causal effect of vitamin D on perinatal, metabolic, vascular and bone health
Proposal summary: 

This grant will be submitted as DA Lawlor's main MRC programme grant for 2008 as part of the MRC Centre for Causal Analyses in Translational Research. It is concerned with determining the causal effect of vitamin D on perinatal outcomes (gestational diabetes, pre-eclampsia, variations in blood pressure during the antenatal period, intrauterine growth retardation, preterm delivery), vascular outcomes (variations in blood pressure, endothelial function, carotid intima media thickness), metabolic outcomes (variations in fasting glucose, insulin, pro-insulin, lipids) and skeletal health (variations inpeak bone mass and fracture risk in later lifeassessed by DXA scan andcortical bone geometry, and hence bone strength assessed bypQCT). Data from ALSPAC offspring and mothers other relevant studies that are linked to the MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE) will contribute to the programme. Our specific objectives are:

1. To use bioinformatics and genome wide association studies to identify genetic variants that are associated with vitamin D levels.

2. To replicate the association of these variants with vitamin D levels in ALSPAC mothers and offspring.

3. To use the genetic variants, identified in 1 and tested in 2 above, as instrumental variables to determine the causal effect of vitamin D on perinatal outcomes (gestational diabetes, pre-eclampsia, variations in blood pressure during the antenatal period, intrauterine growth retardation, preterm delivery)using data from ALSPAC, Danish National Birth Cohort, the Norwegian Birth Cohort and the Born in Bradford Cohort.

4. To use the genetic variants, identified in 1 and tested in 2 above, as instrumental variables to determine the causal effect of vitamin D on vascular outcomes (variations in blood pressure, endothelial function, carotid intima media thickness)using data from ALSPAC (offspring and mothers), the Cardiovascular Risk in Young Finns study, the 1958 UK birth cohort and other CAiTE based adult cohort studies with these measurements.

5. To use the genetic variants, identified in 1 and tested in 2 above, as instrumental variables to determine the causal effect of vitamin D on metabolic outcomes (variations in fasting glucose, insulin, pro-insulin, lipids)using data from ALSPAC (offspring and mothers), the Cardiovascular Risk in Young Finns study, the 1958 UK birth cohort and other CAiTE based adult cohort studies with these measurements.

6. To use the genetic variants, identified in 1 and tested in 2 above, as instrumental variables to determine the causal effect of vitamin D on skeletal outcomes(variations inpeak bone mass and fracture risk in later lifeassessed by DXA scan andcortical bone geometry, and hence bone strength assessed bypQCT). Data from ALSPAC mothers and offspring will be used for this objective.

Date proposal received: 
Sunday, 8 July, 2007
Date proposal approved: 
Sunday, 8 July, 2007
Keywords: 
Primary keyword: 

B524 - Linkage of polymorphisms of PMCH with asthma and obesity - 08/07/2007

B number: 
B524
Principal applicant name: 
Prof Tak Lee (King's College London, UK)
Co-applicants: 
Dr David Cousins (Not used 0, Not used 0), Ms Hilary Sandig (Not used 0, Not used 0), Prof John Henderson (University of Bristol, UK), Dr Roger Newson (Imperial College London, UK), Prof Seif Shaheen (University of Bristol, UK), Prof John Holloway (University of Southampton, UK)
Title of project: 
Linkage of polymorphisms of PMCH with asthma and obesity
Proposal summary: 

Th1 and Th2 cells are the two main subsets of CD4+ T helper cell and are defined by their cytokine expression patterns. The subsets have different roles in the clearance of pathogens, and their unregulated activation leads to distinct immune pathologies. Th1 cells express IFNgamma and are crucial for the phagocytic immune response against intracellular pathogens such as M. tuberculosis, but their aberrant activation is implicated in autoimmunity. Human Th2 cells express IL-4, IL-5 and IL-13 and orchestrate an immune response characterized by eosinophilia and IgE class-switching, in order to fight extracellular pathogens. Th2 cell activation is also central to the pathogenesis of allergic diseases such as asthma, in which the Th2 cytokines play important roles.

PMCH encodes a pro-hormone, pro-melanin concentrating hormone (PMCH) of 165 amino acids which is proteolytically processed to form several peptides including the orexigenic peptide melanin concentrating hormone (MCH). PMCH was first implicated in the regulation of appetite by the finding that the gene is upregulated in obese, leptin deficient mice. Further studies demonstrated that intracerebroventricular administration of MCH into rats increases feeding, and weight gain occurs after chronic infusion of the peptide into the lateral ventricle, strongly suggesting that the peptide stimulates appetite. In addition, mice deficient in MCH are lean and hypophagic, and animals overexpressing the gene are obese. Several groups cloned the G-protein coupled receptor for MCH termed MCHR1, and MCHR1 deficient mice are resistant to diet induced obesity. A second receptor, MCHR2, was later identified in humans by its homology to MCHR1. MCHR2 is not present in the rodent genomes, but orthologues have been identified in ferret, dog and rhesus monkey, in addition to the human gene. PMCH therefore has an important role in increasing appetite, and a small molecule antagonist of MCHR1 has been shown to reduce feeding and weight gain in rats fed a high fat diet ad libitum.

The prevalence of both asthma and obesity are increasing in the western world, and a link between the two conditions has been proposed and debated. Epidemiological evidence from several studies suggests a positive association between body mass index (BMI) and asthma, especially in females (1). Mechanisms to explain the association are unknown.

Utilizing microarray analysis of in vitro differentiated Th1 and Th2 cells to identify secreted proteins selectively expressed by human Th2 cells, we found for the first time that activated Th2 cells expressed the gene PMCH. Activated Th2 cells secreted MCH-containing proteins, and ex vivo Th2 but not Th1 cells also expressed the gene.

PMCH gene is located on chromosome 12q23.1, a region consistently shown to have linkage to asthma. We hypothesize that expression of PMCH by Th2 cells in vivo in the asthmatic lung may provide a mechanistic link between allergic inflammation, asthma and obesity. Asthmatic individuals are not necessarily obese, however, therefore we wish to test whether there are genetic polymorphisms of PMCH that are associated with both asthma and obesity. As expected, a positive association between BMI and asthma in girls at 7 years of age has been confirmed in ALSPAC (AJ Henderson, unpublished data).

Date proposal received: 
Sunday, 8 July, 2007
Date proposal approved: 
Sunday, 8 July, 2007
Keywords: 
Allergies, Genetics, Respiratory, Atopy
Primary keyword: 

B520 - An investigation into the relationship between growth and dental caries - 02/07/2007

B number: 
B520
Principal applicant name: 
Prof Elizabeth Kay (Peninsula Medical School, University of Plymouth, UK)
Co-applicants: 
Prof Andy Ness (University of Bristol, UK)
Title of project: 
An investigation into the relationship between growth and dental caries
Proposal summary: 

Introduction:

The study planned is an analysis of existing data within the Avon Longitudinal Study of Parents and Children (ALSPAC). The aim is to examine the growth rates of children with and without dental caries from birth until the age of five years.

The hypothesis-generating observation that stimulated the proposed study was that weight and body mass index appeared to increase following removal of diseased teeth (1). The proposed study is required because in the original observational study it was not possible, for ethical reasons, to have a control group i.e. the ethical committee found it unacceptable to observe disease in children's mouths without offering a treatment service to them. Since funding to provide such a service was unavailable the study had to utilize population data for the reference group. The best reference population data available was the UK 90 growth reference data. However, the findings of the study have such profound policy implications that it is important to explore the hypothesis of a caries/growth association with high quality data such as ALSPACs as the weaknesses in the former study cast doubt upon the crucially important findings.

Method:

The growth measurements of the children will be converted to percentiles and SD scores. L grow software will then be used to calculate longitudinal norms and to judge the growth pattern of the participants. The average velocity of growth calculated from their height, weight and body mass index at 4, 8, 12 monthly and 6 monthly thereafter until the age of five for each individual will be correlated with their measured dmfts. The children's gender, maternal and partner social class, maternal education, maternal age, maternal and partner height, breast feeding, ethnic group on growth and their effect on caries rates will also be determined.

Thus the relationship between growth and dental caries can be established as well as the extent to which poor oral health is associated with either abnormal body mass index or acceleration/ deceleration in growth.

Sample Size: the number of children will be between 300 (with complete data) and 800 with data on some measurement occasions

Percentile curves on growth charts are spaced 0.67 of a SD apart. The sample size is therefore calculated for a change in SD score of 0.67 units (one percentile space) assuming a correlation between the SD measure on two occasions of 0.80.

A sample size of 20 in each of two groups would have 96% power to detect a difference in means of 0.67 assuming the common standard deviation was 0.63 using a two group t test with two sided significance. Thus in order to allow analysis and comparison of up to 5 sub groups, a sample size of 200 is suggested.

sample. (1) Childhood Growth and Dental Caries. Mohammadi M and Kay E Comm Dent Hlth (in press)

Date proposal received: 
Monday, 2 July, 2007
Date proposal approved: 
Monday, 2 July, 2007
Keywords: 
Primary keyword: 

B530 - Early Growth genetic and environmental determinants of sex hormone and growth factor exposure during puberty - 01/07/2007

B number: 
B530
Principal applicant name: 
Prof David Dunger (University of Cambridge, UK)
Co-applicants: 
Ken Ong (University of Cambridge, UK), Dr Hany Lashen (University of Sheffield, UK), Prof Tim Cole (University of Bristol, UK), Prof Jeff Holly (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK), Prof Andy Ness (University of Bristol, UK)
Title of project: 
Early Growth, genetic and environmental determinants of sex hormone and growth factor exposure during puberty
Proposal summary: 

No outline received

Date proposal received: 
Sunday, 1 July, 2007
Date proposal approved: 
Sunday, 1 July, 2007
Keywords: 
Endocrine, Genetics, Obesity, Weight
Primary keyword: 

B519 - Prediction of drinking outcomes in ALSPAC - 26/06/2007

B number: 
B519
Principal applicant name: 
Prof Marc Schuckit (University of California, San Diego, USA)
Co-applicants: 
Title of project: 
Prediction of drinking outcomes in ALSPAC
Proposal summary: 

Our 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.

1. Age 11 (KW file) and age 13 (TA file) for all SDQ scores. Of particular importance are summarizing scores for externalizing and internalizing symptoms. We do not need specific items. The variables we would like include KW6600a to KW6605c. NOTE: I could not locate the SDQ variables for the 13-year clinic (TA file).

2. Stop-Signal (SS Task Score) from the 10-year clinic. Specifically, we need the number of failures for the hard and easy inhibition items. The specific variable names are: FDCM210 to FDCM222 and FDCM230 to FDCM233.

3. Scores for the TEA-CH test of Sky Search, Sky Search Dual Task, and Opposite Worlds Task from the 11-year clinic. These include variables FEAT060 to FEAT065, FEAT141, FEAT146 to FEAT148, FEAT225, FEAT226, FEAT228, FEAT229.

4. Scores from the Counting Span Task at the 10-year clinic. These variables are FDCM110, FDCM111, FDCM130 to FDCM133.

5. The mother's alcohol, nicotine, and cannabinol use at 18 weeks gestation, as well as the alcohol and nicotine use at 32 weeks gestation. It would also be valuable to have the mother's use of heroin, cocaine, amphetamines, or other drugs at 18 weeks gestation. The variable names for these items include B650 to B679, B700 to B714, B720 to B724, B752 to B760, B767 to B769, C361 to C373, C490, C491, C492.

6. From the puberty questionnaire (including Tanner) scores at the 11-year and 13-year clinics. Specific names include PUB407 to PUB497. NOTE: I could not locate the puberty variables for the 13-year clinic.

7. From the Arnett Sensation Seeking data, variables would include: FESS020 to FESS039, FESS050, FESS051.

Date proposal received: 
Tuesday, 26 June, 2007
Date proposal approved: 
Tuesday, 26 June, 2007
Keywords: 
Alcohol, Smoking
Primary keyword: 

B517 - Qualitative survey of use of cannabis and tobacco among adolescents in ALSPAC - towards assessing feasibility of developing and extending a tobacco peer-led intervention ASSIST to preveting cannabis and tobacco use - 25/06/2007

B number: 
B517
Principal applicant name: 
Prof Matt Hickman (University of Bristol, UK)
Co-applicants: 
Title of project: 
Qualitative survey of use of cannabis and tobacco among adolescents in ALSPAC - towards assessing feasibility of developing and extending a tobacco peer-led intervention (ASSIST) to preveting cannabis and tobacco use
Proposal summary: 

No outline received

Date proposal received: 
Monday, 25 June, 2007
Date proposal approved: 
Monday, 25 June, 2007
Keywords: 
Alcohol, Drugs, Smoking
Primary keyword: 

B516 - Maternal thyroid levels and development outcome of offspring - 25/06/2007

B number: 
B516
Principal applicant name: 
James Sargent (Not used 0, Not used 0)
Co-applicants: 
Pamela Jenkins (Not used 0, Not used 0)
Title of project: 
Maternal thyroid levels and development outcome of offspring
Proposal summary: 

Specific Aims:

1. To determine the levels of maternal thyroid function tests which result in impaired development of the offspring.

a. To determine the levels of TSH, free thyroxine, thyroglobulin, and thyroid peroxidase antibody in the sera of pregnant women at known times in the pregnancy

b. To compare maternal thyroid function with the neurodevelopment of the child at age 8 years, and determine the association between maternal thyroid levels and specific effects in domains of IQ, attention, behavior, speech and language skills, social cognition, gender behavior, executive function, and manual dexterity in the ALSPAC dataset, controlling for potential confounders such as maternal smoking status and socioeconomic status.

c. To determine which maternal factors (e.g. age, antibody status) and offspring factors (e.g. gender) modify the relationship between trimester-specific thyroid status and development of the offspring.

2. To determine the levels of maternal thyroid function tests which result in fetal demise.

3. To develop trimester-specific normative ranges for thyroid hormone levels during pregnancy, based on the relationship with impaired development and fetal loss.

Date proposal received: 
Monday, 25 June, 2007
Date proposal approved: 
Monday, 25 June, 2007
Keywords: 
Endocrine, Weight, Obesiy
Primary keyword: 

B515 - Risk factor modelling of the devlopment of atelectasis and retraction of the tympanic membrane usign the ALSPAC dataset - 25/06/2007

B number: 
B515
Principal applicant name: 
David Pothier (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Risk factor modelling of the devlopment of atelectasis and retraction of the tympanic membrane usign the ALSPAC dataset
Proposal summary: 

No outline received

Date proposal received: 
Monday, 25 June, 2007
Date proposal approved: 
Monday, 25 June, 2007
Keywords: 
Genetics, Autism, Development, Neurology, Vision, Moto Co-ordination
Primary keyword: 

B506 - The effects of dietary factors on bone development in children and their mothers The Avon Longitudinal Study of Parents and Children - 22/06/2007

B number: 
B506
Principal applicant name: 
Dr Kate Northstone (University of Bristol, UK)
Co-applicants: 
Dr Pauline Emmett (University of Bristol, UK), Dr Jon Tobias (University of Bristol, UK), Prof Jean Golding (University of Bristol, UK)
Title of project: 
The effects of dietary factors on bone development in children and their mothers: The Avon Longitudinal Study of Parents and Children
Proposal summary: 

We propose to examine the following research question:

What aspects of the child's diet are related to bone structure in children either before and/or during puberty (depending on when the measures were made)?

Aspects of the diet will include:

  • Overall assessment of the diet using dietary patterns
  • Individual nutrients
  • Individual foods and food groups
  • Longitudinal measures of dietary effects (from prenatal to the current time)

Aspects of the bone structure to be examined will include:

  • Bone size (assessed by area of the whole skeleton derived from total body DXA scans, width of the femoral neck derived from DXA scans of the hip, and cross sectional area of the tibia derived from pQCT scans).
  • Bone shape (reflected by the ratio of length and width of the humerus based on a novel method we have recently developed19).
  • Cortical thickness (based on hip DXA scans and tibial pQCT scans).
  • Trabecular bone mass (based on bone mineral density (BMD) of the spine obtained from sub-regional analysis of total body DXA scans).
  • Bone strength (reflected by cross sectional moment of inertia derived from hip DXA scans and tibial pQCT scans).
Date proposal received: 
Friday, 22 June, 2007
Date proposal approved: 
Friday, 22 June, 2007
Keywords: 
Diet, Eating disorders
Primary keyword: 

B511 - Infant feeding rapid weight gain and obesity - 11/06/2007

B number: 
B511
Principal applicant name: 
Z Maalouf (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Infant feeding, rapid weight gain and obesity
Proposal summary: 

No outline received

Date proposal received: 
Monday, 11 June, 2007
Date proposal approved: 
Monday, 11 June, 2007
Keywords: 
Diet, Weight, Eating disorders
Primary keyword: 

B509 - Adverse clinical risk identification and utilisation for bespoke eye health strategies - 08/06/2007

B number: 
B509
Principal applicant name: 
John Sparrow (University of Bristol, UK)
Co-applicants: 
Title of project: 
Adverse clinical risk identification and utilisation for bespoke eye health strategies
Proposal summary: 

No outline received

Date proposal received: 
Friday, 8 June, 2007
Date proposal approved: 
Friday, 8 June, 2007
Keywords: 
Neurology, Vision, Moto Co-ordination
Primary keyword: 

B510 - Do anxiety and depression associated with previous miscarriage resolve following the birth of a health child - 06/06/2007

B number: 
B510
Principal applicant name: 
Dr Tom O'Connor (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Do anxiety and depression associated with previous miscarriage resolve following the birth of a health child?
Proposal summary: 

No outline received

Date proposal received: 
Wednesday, 6 June, 2007
Date proposal approved: 
Wednesday, 6 June, 2007
Keywords: 
Depression, Mental Health
Primary keyword: 

B547 - CCR5 delta 32 mutation and immune related outcomes Is there a link - 05/06/2007

B number: 
B547
Principal applicant name: 
Dr Martin R??sli (University of Bern, Switzerland, Europe)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK), Prof Matthias Egger (University of Bern, Switzerland, Europe), Prof Claudia Kuenhi (University of Bern, Switzerland, Europe)
Title of project: 
CCR5 delta 32 mutation and immune related outcomes: Is there a link?
Proposal summary: 

The aim of this study is to investigate whether the CCR5 ?32 mutation is associated with immune related phenotypic outcome. It was proposed that abrogation of CCR5 bias the immune system toward a T-helper-2-driven response(Lucotte and Mercier, 1998). As a consequence we hypothesize that the presence of a CCR5?32 mutation is negatively correlated with the incidence of viral childhood infections and positively correlated with atopic disorders. Corresponding phenotypic outcomes will be obtained from the child-based questionnaires completed by a parent at different ages as well as from biological samples (e.g. skin prick test, IgE). Effect modification by environmental exposure will be investigated. The data will be analyzed using established statistical methods for genetic studies, primarily via regression models adjusted for potential confounding factors. Potential population admixture will be allowed for in the analysis.

Genotyping will be done until end of July. Subsequently the analysis will be performed. The results will published in a scientific journal.

Date proposal received: 
Tuesday, 5 June, 2007
Date proposal approved: 
Tuesday, 5 June, 2007
Keywords: 
Genetics
Primary keyword: 

B528 - 1958 DNA distribution - 01/06/2007

B number: 
B528
Principal applicant name: 
Dr Susan Ring (University of Bristol, UK)
Co-applicants: 
Title of project: 
1958 DNA distribution
Proposal summary: 

The British 1958 birth cohort1 is based on all persons born in Britain during one week in March in 1958. Participants have been followed throughout their lives and biomedical information has been collected at various time points. Biological samples were collected from the cohort during medical examinations between Sept 2002 and March 2004. Funding for creation of a blood derived DNA bank was provided by the MRC (strategic project grant G0000934). Funding for creation of lymphoblastoid cell lines, cell line derived DNA extraction, banking and distribution was funded by the Wellcome Trust (grant no 068545).

DNA and cell line banks were created in the ALSPAC Laboratory. Blood derived DNA is available from 8018 individuals and has been used successfully in several genotyping studies.

Cell lines from 2288 individuals were created at ECCAC, Porton and a further 5239 in the ALSPAC laboratory. DNA has been extracted from all of these samples and has been organised into geographically representative subgroups of samples specifically for use as control samples in case control studies. Samples have been distributed to over 20 collaborators and were used as control samples by the Wellcome Trust Case Control Consortium2.

Further funding was obtained in 2006 for management of the cell line and DNA banks and distribution of samples (grant details). This funding will end on 31st August 2007 and we are therefore applying for additional funds to continue these functions.

Date proposal received: 
Friday, 1 June, 2007
Date proposal approved: 
Friday, 1 June, 2007
Keywords: 
Genetics
Primary keyword: 

B512 - Vigorous physical activity increases fracture risk in children independently of bone mass - 31/05/2007

B number: 
B512
Principal applicant name: 
Dr Emma Clark (University of Bristol, UK)
Co-applicants: 
Title of project: 
Vigorous physical activity increases fracture risk in children independently of bone mass
Proposal summary: 

No outline received

Date proposal received: 
Thursday, 31 May, 2007
Date proposal approved: 
Thursday, 31 May, 2007
Keywords: 
Bones, Physical Activity, Physical Fitness, Exercise & Fitness
Primary keyword: 

B502 - The impact of domestic violence during pregnancy on child development - 30/05/2007

B number: 
B502
Principal applicant name: 
Dr Louise Howard (King's College London, UK)
Co-applicants: 
Prof Debbie Sharp (Not used 0, Not used 0), Prof Gene Feder (University of Bristol, UK), Dr Jonathan Evans (University of Bristol, UK)
Title of project: 
The impact of domestic violence during pregnancy on child development
Proposal summary: 

Background: Domestic violence may start or increase in severity during pregnancy (Gazmararian et al 1996; Bowen et al, 2005). The main health effect specific to domestic violence during pregnancy is the threat to health and risk of death of the mother, foetus, or both, from trauma (El Kady et al, 2005; Pearlman et al, 1990). Domestic violence is also associated with depression, anxiety, insomnia, alcohol and drug abuse, and suicide attempts (Campbell 2002). However, the impact of domestic violence during pregnancy on the risk ofchild development has not been previously investigated to our knowledge. A recent study has reported, though, on the significant impact of postnatal domestic violence on child development, which, with postnatal depression, had a cumulative effect, leading to worse child outcome (Whitaker et al, 2006). There is increasing evidence that prenatal stress and major depression during pregnancy are associated with increased concentrations of corticotrophin releasing hormone (O'Keane et al, submitted); this increase in pituitary-adrenal activity may explain the association of domestic violence during pregnancy with poor obstetric outcomes (low birthweight and preterm pregnancy) . Domestic violence may therefore adversely affect child development independent of the effect of antenatal psychiatric morbidity or subsequent psychiatric morbidity, but any effects on child development may also be partly mediated by antenatal psychiatric morbidity.

Date proposal received: 
Wednesday, 30 May, 2007
Date proposal approved: 
Wednesday, 30 May, 2007
Keywords: 
Primary keyword: 

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