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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B580 - Tonsillectomy for recurrent paediatric tonsillitis - does it work The ALSPAC experience - 06/11/2007

B number: 
B580
Principal applicant name: 
(Not used -1, Not used -1)
Co-applicants: 
Prof Mark Griffiths (Not used 0, Not used 0)
Title of project: 
Tonsillectomy for recurrent paediatric tonsillitis - does it work? The ALSPAC experience
Proposal summary: 

Background:

Debate continues as to the benefit of tonsillectomy. A recent Cochrane review found that there were insufficient trials to fully evaluate the effectiveness of tonsillectomy (1). However, the author of the only studies included in this review stand by their conclusion that tonsillectomy was efficacious in reducing sore throat episodes (1). Furthermore, recent comment from a leading ENT academic asks the pertinent question of the whether the perceived supremacy of this type of review for answering questions related to the use of surgical interventions is justified (2).

Primary question:

Is there a manifest, bias balanced benefit from tonsillectomy versus non-operative management for children with recurrent tonsillitis?

Rationale for using ALSPAC data:

Although there are many studies into the benefit of tonsillectomy, we believe that the ALSPAC database will contain information to add significantly to this debate. Last year there were nearly 30,000 tonsillectomies carried out across England in the 0-14 age group (3). Assuming the national average rate of tonsillectomy applies to the ALSPAC population we expect around 300 tonsillectomies to have been performed on this cohort of children. This study size is comparable with other studies (1).

The incidence of self-reported sore throat is included in the questionnaires, this is the primary outcome that has been previously used to assess benefit of the intervention. However, other outcome measures such as SAT scores and school attendance may be used to demonstrate an association with tonsillectomy. Also, confounders such as socio-economic and smoking status may be examined to balance any potential bias.

Plan of action:

1. We intend to review the ALSPAC database to ascertain the incidence of the exposure variable (tonsillectomy) and the outcome measure (primary being reported sore throat episodes, secondary measures being school attendance/performance).

2. Assess likely bias from confounders between groups.

3. Extract data.

4. Statistical analysis (3. and 4. to be supported by the ALSPAC statistics team, funded by the applicants).

5. Presented locally, regionally and nationally.

6. Publish in the ENT-UK journal (Clinical Otolaryngology).

Date proposal received: 
Tuesday, 6 November, 2007
Date proposal approved: 
Tuesday, 6 November, 2007
Keywords: 
Hearing
Primary keyword: 

B575 - Peri pubertal hip geometry in the ALSPAC Cohort - 25/10/2007

B number: 
B575
Principal applicant name: 
Dr Jon Tobias (University of Bristol, UK)
Co-applicants: 
Title of project: 
Peri pubertal hip geometry in the ALSPAC Cohort
Proposal summary: 

Several studies in ALSPAC have revealed significant effects of different factors on bone size as assessed by DXA measurements. Interestingly, effects such as social position persist after adjustment for height, suggesting an influence on bone width (1). This observation is important, since influences on bone width imply that bone shape and geometry are being affected, which may have important implications for the risk of sustaining osteoporotic fractures in later life. Therefore, we are keen to explore potential influences on bone geometry in ALSPAC in more detail.

Initial time constraints in the focus clinics limited the acquisition of all three bone scans (Total body and Hip DXA, and PQCT) mainly due to the unfamilarity of the PQCT scanner, therefore we were limited to using only total body DXA and PQCT. However now the operators have become more familiar with the PQCT scanner the length of time required complete this section has been reduced. Therefore at the end of, and breaks in each clinic session there is now time to perform a unilateral hip DXA scan.

Currently total body DXA scans are being performed, and although total body DXA provides important information about bone density in the body it does not provide any information about the shape and strength of the bone. Other groups are currently measuring physical activity within the cohort and it is postulated that bone adapts to the functional requirements placed upon it. The hip is a key area linking the peripheral and axial skeleton together, and due to the geometric orientation of the hip functional stress and strains are very large, and therefore have the potential to show the greatest adaptation to these stresses and strain.

We are currently investigating the effects of physical activity on bone shape and geometry using pQCT as part of a welcome grant. However pQCT is confined to the use of the peripheral skeleton and we can only measure the tibia. Whilst the information gained from this part of the investigation is important due to the direct measurement of shape and geometry, it can not be used to infer information about the hip. Although hip DXA does not directly measure geometry unlike the pQCT, these parameters can be estimated, therefore we are keen to incorporate this scan into the current clinic, especially as there are no extra associated costs incu

We would like to include a unilateral hip DXA, time permitting, in the densitometry element of the data collection clinic. We are proposing to perform all 3 scans in the Age 17 clinic, and have previously collected information on hip geometry at age 13/14. By collecting hip geometry information at age 15/16 we will be better able to investigate the growth and development of bone whilst the young people are going through puberty, and how this may influence osteoporotic fractures later in life.

Hip DXA uniquely estimates the strength and cross sectional area of the hip, this aspect of bone geometry cannot be obtained via the PQCT or the total body DXA. The hip is commonly associated with osteoporotic fractures later in life and th

Date proposal received: 
Thursday, 25 October, 2007
Date proposal approved: 
Thursday, 25 October, 2007
Keywords: 
Physical Activity, Physical Fitness, Exercise & Fitness
Primary keyword: 

B577 - Public Health Consequences of Modifiable Maternal Exposures Offspring Obesity and Cognitive Health in the UK and Brazil - 24/10/2007

B number: 
B577
Principal applicant name: 
Dr Marie-Jo Brion (University of Bristol, UK)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK), Prof Debbie A Lawlor (University of Bristol, UK), Dr Sarah J Lewis (University of Bristol, UK)
Title of project: 
Public Health Consequences of Modifiable Maternal Exposures: Offspring Obesity and Cognitive Health in the UK and Brazil
Proposal summary: 

Research Programme.The aim of his project is to:

1)Increase the strength of causal inference regarding associations between modifiable maternal exposures (medication and supplement use, diet, smoking, alcohol consumption, physical activity) and offspring obesity, psychological health and cognitive function.

2) Formally compare these associations in a cohort from LMIC (Brazil) and one from HIC (Britain).

I (under the supervision of Professors Davey Smith, Victora, Lawlor, and Drs Lewis and Matijasevich) will implement this utilising:

1) Maternal and child data collected prospectively in the ALSPAC cohort in Britain and Pelotas cohort in Brazil.

2) Using two methods that can provide more robust causal inference regarding effects of maternal intrauterine effects that can be obtained from conventional observational epidemiology approaches11.

a. Comparison of maternal behaviour-offspring outcome associations to paternal behaviour-offspring outcomes. The idea behind this approach is that specific maternal intrauterine effects should result in stronger associations between maternal behaviour-offspring outcome and paternal behaviour-offspring outcome. I have used this approach once in my PhD work12 and would like to develop this relatively novel approach, including more sophisticated statistical modelling (e.g. to account for possible non-paternity further).

b. Use of genetic variants that are related to maternal modifiable exposures as instrumental variables to determine the causal effect of the maternal modifiable exposure. Mendelian randomisation has been proposed as one way of overcoming confounding by utilising the random allocation of alleles from parent to offspring13. Certain genetic variants can be found to affect behaviours e.g. LCT genotype and lactose-containing foods14. Genetic variants such as these can be used as instrumental variables for maternal behaviours, and provide a means for testing an unconfounded and unbiased association with components of offspring health.

ALSPAC. ALSPAC data that would be required for this proposed outline include maternal and paternal questionnaire data on health and behaviours during pregnancy (medication and supplement use, diet, smoking, alcohol) and clinic data in the children relating to size and obesity (BMI, body fat, lean mass, trunk fat etc) as well as psychological measures (depression, anxiety, cognitive function). In addition, genetic data from the DNA samples that are currently being collected in both mothers and children would be required.Pelotas cohort, Brazil.One of the largest and longest running birth cohorts in the developing world, this cohort consists of 5914 infants born in 1982 in the Brazilian city of Pelotas. Follow-up assessments (in varying numbers of children) have been carried out at varying stages of development ranging from at birth, infancy and childhood (age ranges from less than 1 year to 5 years), adolescence (12 to 19 years) and young adulthood (22 to 24 years). A wide range of information is available, including family socioeconomic position, maternal characteristics, maternal health and behaviours in pregnancy, infant perinatal data, environmental factors, infant nutrition, as well as physical and psychological measures in infancy, childhood and adolescence. Similar data is also available in another Pelotas cohort initiated in 1993.DNA samples will be collected in a planned follow up study in 2008.Existing collaborations between ALSPAC and Pelotas.There is enormous potential (given the similarity of design and measurements in the two studies) for scientifically valuable collaborations between these two cohorts, and the two scientific directors (Davey Smith and Victora) are eager to facilitate and support such collaboration. With an award by the Wellcome Trust for Dr Alicia Matijasevich, who works with Professor Victora on the Pelotas cohort to spend six months in Bristol on a project comparing socioeconomic differentials of maternal and childhood outcomes between the two cohorts. I intend to build upon this work in the current proposal and further strengthen collaborations between the two cohorts.

Date proposal received: 
Wednesday, 24 October, 2007
Date proposal approved: 
Wednesday, 24 October, 2007
Keywords: 
Diet, Eating Disorder
Primary keyword: 

B576 - Dietary patterns in early childhood and IQ - 23/10/2007

B number: 
B576
Principal applicant name: 
Dr Kate Northstone (University of Bristol, UK)
Co-applicants: 
Dr Carol Joinson (University of Bristol, UK), Dr Pauline Emmett (University of Bristol, UK), Dr Tomas Paus (Not used 0, Not used 0), Prof Jean Golding (University of Bristol, UK)
Title of project: 
Dietary patterns in early childhood and IQ
Proposal summary: 

There have been several studies showing the effects of vitamin supplementation, nutrient deficiency and recent dietary intake on IQ in children [see 1 for a review]. We have recently shown in the ALSPAC cohort that overall dietary patterns in early childhood are associated with both later child behaviour and school performance [2,3]. There appears to be little known about the long-term effects of early diet (with the exception of infant feeding) on later child cognition, as assessed by IQ. The use of dietary patterns aims to overcome the inherent problems of examining individual food and nutrients associations, namely, the inter-correlations between these foods and nutrients. The proposed analysis provides a novel approach to examining the effects of dietary intake on cognitive development.

A preliminary analyses assessing the effects of childhood dietary patterns on IQ has already performed in order to feed into a grant proposal to be submitted to NIH in Feb 08 by Tomas Paus (Nottingham), a primary aim of which is to evaluate the role of nutrition during the first five years of life on brain structure in adolescence.

At his request, I examined the associations between dietary patterns in early childhood (at ages 3, 4, 7 and 8 years [4,5]) and overall IQ assessed at 8 years of age. Initial results suggest that there may be an effect of overall dietary patterns in childhood and IQ. In particular a 1 SD increase in the 'processed' component score at each age (3, 4, 7 and 8) was associated with a decrease of between 2 and 4 points on the WISC IQ scale, while a 1 SD increase in 'health conscious' component score at each age resulted in a 2 point increase. After adjustment for a limited number of confouding or mediating factors the effect sizes were attenuated, though strong relationships remained the 3-year data; as such further analyses is required to take into account additional factors which may be important after a thorough review of the literature. This will determine whether the observed effects are real or due to residual confounding.

Proposed further anlaysis will include:

1. Examining the verbal and performance components of the WISC;

2. Examining the results of the subtests of the WISC;

3. Further adjustment for other factors, including maternal diet, aspects of which have been shown to be associated with IQ in this sample [6];

4. Using cut-offs for IQ in order to determine the risk of poor performance.

Although this work is unfunded it will be of particular use to the NIH grant and is a natural follow-on to the work constituting my PhD. It will also feed into other funding opportunities to investigate the effects of diet on other cognitive and neuro-developmental outcomes.

Date proposal received: 
Tuesday, 23 October, 2007
Date proposal approved: 
Tuesday, 23 October, 2007
Keywords: 
Physical Activity, Physical Fitness, Exercise & Fitness, Diet, Eating disorders
Primary keyword: 

B572 - Enviromental determinants of physcial activity - 22/10/2007

B number: 
B572
Principal applicant name: 
Dr Melvin Hillsdon (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Enviromental determinants of physcial activity
Proposal summary: 
Date proposal received: 
Monday, 22 October, 2007
Date proposal approved: 
Monday, 22 October, 2007
Keywords: 
Physical Activity, Physical Fitness, Exercise & Fitness
Primary keyword: 

B571 - The ontogeny of paranoid delusions - 22/10/2007

B number: 
B571
Principal applicant name: 
Prof Richard Bentall (University of Liverpool, UK)
Co-applicants: 
Dr Charles Fernyhough (University of Durham, UK), Emma Barkus (Institute of Psychiatry, King's College London, UK), Shon Lewis (University of Manchester, UK), Nick Shryane (University of Manchester, UK), Prof Glyn Lewis (University of Bristol, UK), Prof Glynn Harrison (University of Bristol, UK)
Title of project: 
The ontogeny of paranoid delusions
Proposal summary: 

No outline received

Date proposal received: 
Monday, 22 October, 2007
Date proposal approved: 
Monday, 22 October, 2007
Keywords: 
Depression, Mental Health
Primary keyword: 

B672 - Enviromental determinants of physcial activity - 22/10/2007

B number: 
B672
Principal applicant name: 
Dr Melvin Hillsdon (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Enviromental determinants of physcial activity
Proposal summary: 
Date proposal received: 
Monday, 22 October, 2007
Date proposal approved: 
Monday, 22 October, 2007
Keywords: 
Physical Activity, Physical Fitness, Exercise & Fitness
Primary keyword: 

B467 - Prevalence of antimicrobial resistance in bacteria in healthy humans and identifying risk factors that are contributing to the carriage andpersistence of antimicrobial genes in human - 19/10/2007

B number: 
B467
Principal applicant name: 
Anne Delsol (Not used 0, Not used 0)
Co-applicants: 
Title of project: 
Prevalence of antimicrobial resistance in bacteria in healthy humans and identifying risk factors that are contributing to the carriage and persistence of antimicrobial genes in human
Proposal summary: 

No outline received

Date proposal received: 
Friday, 19 October, 2007
Date proposal approved: 
Friday, 19 October, 2007
Keywords: 
Primary keyword: 

B573 - Preterm Birth Whole Genome Association Study - 16/10/2007

B number: 
B573
Principal applicant name: 
Dr Caroline Relton (University of Bristol, UK)
Co-applicants: 
Title of project: 
Preterm Birth Whole Genome Association Study
Proposal summary: 

No outline received

Date proposal received: 
Tuesday, 16 October, 2007
Date proposal approved: 
Tuesday, 16 October, 2007
Keywords: 
Genetics
Primary keyword: 

B569 - Genetic and environmental influences on developmental trajectories of alcohol use misuse and related behaviours - 15/10/2007

B number: 
B569
Principal applicant name: 
Prof Kenneth Kendler (Virginia Commonwealth University, USA)
Co-applicants: 
Title of project: 
Genetic and environmental influences on developmental trajectories of alcohol use, misuse and related behaviours
Proposal summary: 

No outline received

Date proposal received: 
Monday, 15 October, 2007
Date proposal approved: 
Monday, 15 October, 2007
Keywords: 
Alcohol, Drugs, Smoking
Primary keyword: 

B568 - The influence of the enviroment on face shape - 10/10/2007

B number: 
B568
Principal applicant name: 
Prof Stephen Richmond (University of Cardiff, UK)
Co-applicants: 
Dr Alexei Zhurov (University of Cardiff, UK), Prof Andy Ness (University of Bristol, UK), Dr Rebecca Playle (University of Cardiff, UK), Dr Tomas Paus (Not used 0, Not used 0)
Title of project: 
The influence of the enviroment on face shape
Proposal summary: 

No outline received

Date proposal received: 
Wednesday, 10 October, 2007
Date proposal approved: 
Wednesday, 10 October, 2007
Keywords: 
Primary keyword: 

B574 - Variants in the cannabinoid receptor gene and their influence on alcohol and drug consumption - 10/10/2007

B number: 
B574
Principal applicant name: 
(Not used 0, Not used 0)
Co-applicants: 
Dr Martin R??sli (University of Bern, Switzerland, Europe), Prof Matthias Egger (University of Bern, Switzerland, Europe), Prof Debbie A Lawlor (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK)
Title of project: 
Variants in the cannabinoid receptor gene and their influence on alcohol and drug consumption
Proposal summary: 

The CB1 receptor of the endocannabinoid system is known to modulate the endocrine hypothalamic-peripheral endocrine axes. Important advances have been made in our understanding of the endocannabinoid signaling system in various aspects of alcoholism and drug consumption. Alcohol increases the synthesis or impairs the degradation of endocannabinoids, leading to a locally elevated endocannabinoid tone within the brain. Elevated endocannabinoid tone might be expected to result in compensatory down-regulation of CB1 receptors or dampened signal transduction. Following release, endocannabinoids diffuse back to the presynaptic neuron where they act as short-range modulators of synaptic activity by altering neurotransmitter release and synaptic plasticity (Basavarajappa, 2007). Several small studies investigated a potential association between variants on the CNR1 gene and alcohol and/or drug consumption yielding inconsistent results (Herman et al. 2006; Racz et al. 2003; Schmidt et al. 2002; Zhang et al. 2004, Zuo et al. 2007).

We used data from the BWHHS study to evaluate whether two different single nucleotide polymorphisms of the CB1 receptor of the endocannabinoid system (CR1=rs1049353; CR2=rs2023239) are associated with obesity (2 variables), blood measures (9 variables), food intake (22 variables), drug consumption (6 variables) or mood (3 variables). There was no evidence that body mass measures, food intake or mood were related to genetic variants. However the results concerning alcohol and tobacco use are intriguing and merits further clarification.

Methods

Data from the ALSPAC study will be used to evaluate a potential association between variants of the CNR1 gene and alcohol consumption. We will genotype the two SNPs from the previous study (rs1049353; rs2023239) as well as to additional SNPs: rs806368 & rs12720071.The following data from the mother's forty seven month post-natal questionnaire will be investigated: alcoholic drinks (B22), own smoking (F4), passive smoking (D2, F5), drug/cannabis consumption (A3), being currently pregnant (A8).

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 November. Subsequently the analysis will be performed. The results will published in a scientific journal.

Significance

The ALSPAC study has considerable larger sample size than every other previous study on this topic. This candidate gene study will help to understand the role of the endocannabinoid system in the process of addiction. In addition,the study results are relevant regarding the application effects of cannabinoid (CB1) receptor antagonists. For instance a recent Cochrane review found that Rimobanant is helpful for quitting smoking (Cahill & Ussher, 2007).

Date proposal received: 
Wednesday, 10 October, 2007
Date proposal approved: 
Wednesday, 10 October, 2007
Keywords: 
Genetics
Primary keyword: 

B592 - Predictive Value of Questionnaire Data for Assessing Atopic Status - 06/10/2007

B number: 
B592
Principal applicant name: 
Dr Leslie Elliott (Washoe County District Health Department, USA)
Co-applicants: 
Title of project: 
Predictive Value of Questionnaire Data for Assessing Atopic Status
Proposal summary: 

Background: In epidemiological studies, questionnaire data are often used to determine atopic status of participants. When children are study subjects, the information on atopic status is provided by the parents. However, there does not appear to be a literature on the predictive value of a parent's report of allergies. To address this issue, questionnaire data regarding a child's allergy status need to be compared with objective data such as skin prick tests or specific IgE. In addition to obtaining both questionnaire and objective data, the temporal sequence is important for calculating predictive value.

Because of its prospective design, the ALSPAC cohort is ideal for addressing this question. Mothers were asked about their study child's specific allergies at ages 54 months and 81 months. At age 7 years, children attended Focus @7, which included skin prick testing.

Variables related to allergies and allergy symptoms will be used from earlier questionnaires (i.e., 54 months and 81 months) and compared with results of skin prick testing at age 7 years for children who attended the allergy clinic. Wheal size will also be considered. Predictive values of mother's responses at the 54 month and 81 month questionnaires will be calculated. Other variables that may influence a mother's report of child's allergic status will be considered, including mother's self-report of allergy and asthma, paternal allergy and asthma, mother's report of child's asthma, and child's history of wheezing and eczema at younger ages.

Again, I will not need to obtain any variables. All necessary variables were included in the dataset obtained for a project which will be submitted for publication by the end of December, 2007.

Date proposal received: 
Saturday, 6 October, 2007
Date proposal approved: 
Saturday, 6 October, 2007
Keywords: 
Environmental Exposure, Atopy
Primary keyword: 

B567 - How common is CFS/ME at age 13 and what factors increase the risk of developing it - 03/10/2007

B number: 
B567
Principal applicant name: 
Dr Esther Crawley (University of Bristol, UK)
Co-applicants: 
Prof Peter Fleming (University of Bristol, UK), Prof Alan Emond (University of Bristol, UK)
Title of project: 
How common is CFS/ME at age 13 and what factors increase the risk of developing it?
Proposal summary: 

No outline received

Date proposal received: 
Wednesday, 3 October, 2007
Date proposal approved: 
Wednesday, 3 October, 2007
Keywords: 
Primary keyword: 

B566 - An investigation of language-impairment and dyslexia associated SNPs within the general population - 03/10/2007

B number: 
B566
Principal applicant name: 
Prof Anthony P Monaco (University of Oxford, UK)
Co-applicants: 
Dr Silvia Paracchini (University of Oxford, UK), D F Newbury (University of Oxford, UK)
Title of project: 
An investigation of language-impairment and dyslexia associated SNPs within the general population
Proposal summary: 

We are submitting this project proposal to obtain approval to analyse an additional gene for the project "An investigation of language-impairment and dyslexia associated SNPs within the general population".

We are proposing to include in our analysis the CNTNAP2 gene. This gene has recently been associated with language abilities in separate samples of individuals diagnosed with autism spectrum disorders. We have replicated the associations in our sample of families affected by SLI. This gene is located at 7q36 within the AUTS1 locus where several studies have mapped linkage to autism.

The panel of markers selected for the CNTNAP2 is listed at the end of the Appendix together to the other markers already approved for this project. The genotyping will be performed through the Sequenom system using the ALSPAC DNA samples we already have in our laboratory. Due to multiplex assays' constraints alternative markers might be selected to screen the listed genes. The statistical analysis we plan to perform is based on very standard single marker association approaches and will be very similar to what we conducted for the KIAA0319 gene.

Date proposal received: 
Wednesday, 3 October, 2007
Date proposal approved: 
Wednesday, 3 October, 2007
Keywords: 
Genetics
Primary keyword: 

B561 - Genetic contributions to childhood resilience - 01/10/2007

B number: 
B561
Principal applicant name: 
Prof Michael E Lamb (University of Cambridge, UK)
Co-applicants: 
Dr Tim Croudace (Not used 0, Not used 0), Prof Susan Golombok (University of Cambridge, UK), Prof George Davey Smith (University of Bristol, UK)
Title of project: 
Genetic contributions to childhood resilience
Proposal summary: 

During the last decade, a revolution has taken place among clinical and developmental psychologists. Whereas the emphasis was formerly on continuity and stability over time, with earlier experiences uniformly shaping developmental trajectories, many researchers have come to recognise that individuals are not uniformly plastic, so that some are more susceptible than others to influence. In perhaps the most widely cited demonstration of this, Caspi and colleagues showed in a retrospective study in New Zealand that individual differences in a specific genetic allele determined which children would be adversely affected by depriving early life experiences, whereas children without this allele emerged apparently unscathed from similarly debilitating experiences. The clarity of this finding quickly made believers of many researchers who had hitherto viewed with scepticism decades of scholarship on risk and vulnerability by such researchers as Rutter, Gottesman, and Masten, but empirical demonstration of the nature, extent, and limits of susceptibility to influence (both vulnerability and its obverse, strength in the face of adversity) has been limited. The goal of the proposed research is to examine multiple possible sources (both genetic and environmental) of these individual differences and an array of developmental outcomes using a large, representative, and rich data set collected by the ALSPAC team.

For many years (and with differing degrees of emphasis at different times on either side of the Atlantic) students of child development have recognised that psychological and behavioural development are neither predetermined nor infinitely malleable, although infants appear to be born with marked congenital individual differences. Child psychiatrists such as Thomas and Chess devoted their careers to illustrating the impact of such inborn temperamental attributes on children's developmental trajectories, whereas psychologists such as Rothbart have sought to understood the physiological bases of the major dimensions of temperament that have been identified (Rothbart & Bates, 2006). Students of temperament and behaviour genetics have thus emphasized the importance of biogenetic predispositions and have sought to unpack the ways in which experience might, in combination with congenital individual differences, shape children's development, by promoting stability over time (i.e., 'the child is father to the man'), leading some children to develop more poorly than anticipated, or ensuring that some children prosper, doing better than originally expected. To some extent, progress has been impeded by measurement difficulties, particularly by the challenge of making sense of differences between temperamental appraisals provided by parents (reflecting their subjective perceptions of the child) and those obtained through more objective and systematic observational and physiological means.

In addition, the focus has largely been on the temperamental factors that place some children at greater risk of developing behaviour problems, including serious psychological disturbances-especially because they are "difficult" or "irritable"-- and upon the stability of individual differences, that is, the degree to which children remain difficult across infancy, childhood and adolescence. By contrast, considerably less attention has been paid to such positive characteristics as cheerfulness, perseverance, the capacity to love and be loved, or resilience that might presage positive outcomes; and even less empirical work has focused upon the extent to which-and the reasons why-children's characteristics change. Even though developmental psychologists have shown more interest in the positive side of life than have clinical psychologists, investigating such topics as the origins of empathy, prosocial behaviour, and social skills, few researchers have explored why some children change from negative to positive developmental trajectories and vice versa.

Although it is seductive to assume that those most positively or negatively disposed early in life remain that way as they age, new findings reported by Sharp, Croudace, and Goodyer (2007) caution against such potentially simplistic reasoning. Not only were optimistic 7- to 11-year-olds more likely to change their orientations than peers who had an initial 'neutral' orientation, but those who initially scored highest on optimism scored highest on psychopathology two years later. Clearly, one cannot presume that continuity always characterises the process of human development, including positive development.

Attachment theory has played a particularly important role in shaping understanding of the ways in which early experiences (notably, the quality of parental behaviour and of infant-parent interaction) influence the quality of the close, emotional relationships that infants form to each of their attachment figures and which, in turn, help shape children's later social relationships and approaches to other challenging tasks and experiences. Over the last 40 years, and especially since Ainsworth developed the Strange Situation Procedure (SSP) to assess the security of infants' emotional ties ('attachments') to their mothers, fathers and other caregivers, developmental psychologists have made considerable progress in illuminating the origins and predictive implications of individual differences in child development, even those measured very early in life.

Date proposal received: 
Monday, 1 October, 2007
Date proposal approved: 
Monday, 1 October, 2007
Keywords: 
Genetics
Primary keyword: 

B559 - An investigation into the association between prenatal diet height body composition and IGF levels and subsquent cancer risk using a Mendelian randomization approach - 01/10/2007

B number: 
B559
Principal applicant name: 
Dr Sarah J Lewis (University of Bristol, UK)
Co-applicants: 
Prof David Gunnell (University of Bristol, UK), Prof Andy Ness (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK), Prof Jeff Holly (University of Bristol, UK)
Title of project: 
An investigation into the association between prenatal diet, height, body composition and IGF levels and subsquent cancer risk using a Mendelian randomization approach
Proposal summary: 

Outline

Height, body composition and IGF levels have all been shown to be associated with cancer risk, in particular breast and prostate cancer. The extent to which nutrient availability in the prenatal period affects these phenotypes and subsequent cancer risk is largely unknown. Genetic variation can influence dietary intake and metabolism of nutrients, thus affecting exposure to specific dietary components, such variation will be exploited in this project. The advantage of this method is that associations between genetic polymorphisms and height, body composition and IGF levels are not subject to the problems of measurement error, recall bias and confounding.[i] The use of genes as surrogates for measuring exposures in epidemiology has been termed Mendelian Randomisation, and is gaining recognition as an important research tool, marked by the establishment of an MRC Centre for Causal Analyses in Translational Epidemiology at the University of Bristol.

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 milk intake[ii] b) involved in nutrient metabolism, for example the MTHFR gene which is involved in the metabolism of folate,[iii] c) important in the transport and intern

Date proposal received: 
Monday, 1 October, 2007
Date proposal approved: 
Monday, 1 October, 2007
Keywords: 
Primary keyword: 

B558 - The structure and origins of schizotypal personality traits in adolescence - 01/10/2007

B number: 
B558
Principal applicant name: 
Prof Richard Bentall (University of Liverpool, UK)
Co-applicants: 
Dr Charles Fernyhough (Not used 0, Not used 0), Nick Shryane (Not used 0, Not used 0)
Title of project: 
The structure and origins of schizotypal personality traits in adolescence
Proposal summary: 

No outline received

Date proposal received: 
Monday, 1 October, 2007
Date proposal approved: 
Monday, 1 October, 2007
Keywords: 
ADHD, Antisocial Behaviour, Behavioural Problems
Primary keyword: 

B557 - Electronic patient records and database research - 28/09/2007

B number: 
B557
Principal applicant name: 
Mrs Rosie Cornish (University of Bristol, UK)
Co-applicants: 
Prof John Macleod (University of Bristol, UK), Prof John Henderson (University of Bristol, UK)
Title of project: 
Electronic patient records and database research.
Proposal summary: 

Aims

1. Obtain consent for and establish mechanisms of linkage between ALSPAC study participants and routine sources of health and social data to enable enrichment of the study database and cost-effective prospective follow-up.

2. Investigate challenges to linkage based epidemiological research and follow-up of population-based cohorts and develop generalisable solutions to these problems

3. Demonstrate the value of linkage-based research through a series of exemplar projects on key health and social outcomes in young adulthood.

4. Establish a training programme to share these methods and insights with other researchers.

Date proposal received: 
Friday, 28 September, 2007
Date proposal approved: 
Friday, 28 September, 2007
Keywords: 
Diet, Eating disorders, Data Linkage
Primary keyword: 

B560 - Pilot study of ALSPAC hearing data at age 11 work towards grant application - 27/09/2007

B number: 
B560
Principal applicant name: 
Dr Amanda J Hall (University of Bristol, UK)
Co-applicants: 
Prof Adrian Davis (Not used 0, Not used 0), Dr Judith Gravel (Not used 0, Not used 0)
Title of project: 
Pilot study of ALSPAC hearing data at age 11 ? work towards grant application
Proposal summary: 

The aim of the pilot work is to support an application for the proposed 17+ clinic. The following data are required for preliminary analyses:

1. Hearing threshold and hearing questionnaire data collected at the Focus11+ clinic.

2. Sex of child

3. Social status of child

The following analyses will be performed:

1. Comparison of the frequency distribution of hearing threshold at 11 years with the data currently being collected at age 15 years.

2. Comparison of the frequency distributions at age 11 and 15 with similar data from the 1958 cohort study

3. Estimation of the percentage of children with a permanent hearing loss at age 11 years

4. Effect of sex and social status on hearing thresholds at age 11

The results of these analyses will be used as part of a grant application, and may also be written up for publication.

Date proposal received: 
Thursday, 27 September, 2007
Date proposal approved: 
Thursday, 27 September, 2007
Keywords: 
Hearing
Primary keyword: 

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