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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B361 - Androgen Receptor and Behavioural Pubertal Outcomes - 16/05/2006

B number: 
B361
Principal applicant name: 
Dr L G Boothroyd (University of Durham, UK)
Co-applicants: 
Title of project: 
Androgen Receptor and Behavioural, Pubertal Outcomes.
Proposal summary: 

(No outline received).

Date proposal received: 
Tuesday, 16 May, 2006
Date proposal approved: 
Tuesday, 16 May, 2006
Keywords: 
ADHD, Antisocial Behaviour, Biological Samples, Genetics, Puberty, Behaviour Change
Primary keyword: 

B357 - Infancy Data from Children in Focus Study for WHO Chart Comparison - 15/05/2006

B number: 
B357
Principal applicant name: 
Dr Charlotte M Wright (University of Glasgow, UK)
Co-applicants: 
Title of project: 
Infancy Data from Children in Focus Study for WHO Chart Comparison.
Proposal summary: 

(No outline received).

Date proposal received: 
Monday, 15 May, 2006
Date proposal approved: 
Monday, 15 May, 2006
Keywords: 
Endocrine, Growth, Obesity, Weight, Height
Primary keyword: 

B355 - Second Methods Grant Role of placental size and shape in predicting childhood growth - 09/05/2006

B number: 
B355
Principal applicant name: 
Dr Dawn Misra (Wayne State University, USA)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK), Dr Carolyn Salafia (North Carolina State University, USA), Prof David Barker (University of Southampton, UK), Prof Debbie A Lawlor (University of Bristol, UK)
Title of project: 
Second 'Methods' Grant (Role of placental size and shape in predicting childhood growth).
Proposal summary: 

We propose a pilot analysis using the placental data already collected from the Chidlren in Focus subset (CIF, N=1050), and BMI, waist & fat & lean mass (DXA) at age 9. These pilot analyses will provide strong support for our (generally well received) October submission, and we are optimistic about receiving funding based on our July resubmission. Jon Heron and Jeremy Miles will work together on data analysis, which will be incorporated into the July grant that will include Dr Lawlor, Dr Davey-Smoth and potentially Dr David Barker in the research team.

Previously submitted and approved protocol (our ref B355)

We propose to develop an R01 application utilizing placental data to be submitted as a supplement to the NIH funded R01 "Maternal overnutrition and offspring fat mass, metabolic and vascular function" (Principal Investigator: Dr. Debbie Lawlor, University of Bristol). We outline below the specific aims for such a supplement and provide a model illustrating the integration of these aims with the aims of the currently funded study. While Dr. Lawlor's grant aims refer to "offspring" generally, we have explicitly separated out the neonatal (birth outcomes) within our aims given the focus on the placenta.

SPECIFIC AIMS

Specific Aim 1: To investigate the influence of maternal BMI, weight gain, and diet during pregnancy on placental anthropometric measures. Specifically, we will assess and study the following placental parameters: placental weight, thickness, diameters; umbilical cord length; shape; symmetry measures; chorionic vascular branching pattern). The following null hypotheses will be tested:

1A. Maternal BMI does not explain variation in placental size and shape.

1B. Maternal weight gain does not explain variation in placental size and shape.

1C. Maternal diet does not explain variation in placental size and shape.

Specific Aim 2: To determine whether and how placental size and shape influences birth size. The following null hypotheses will be tested:

2A. Placental size and shape are not associated with birth size (e.g. weight, birth weight ratio, length, ponderal index).

2B. Associations between maternal factors and birth size are mediated by variation in placental size and shape.

Specific Aim 3: To determine whether and how placental size and shape influence offspring growth. Offspring growth was measured at multiple time points beginning at age 1 year up to 15 years of age and includes measures of adiposity (DXA assessed fat mass and fat distribution), vascular function (blood pressure, pulse pressure and endothelial function), and metabolic function (fasting glucose, insulin and lipids). The following null hypotheses will be tested:

3A. Placental size and shape are not associated with offspring childhood adiposity.

3B. Placental size and shape are not associated with offspring childhood vascular function.

3C. Placental size and shape are not associated with offspring childhood metabolic function.

3D. Associations between placental size and shape with offspring outcomes are mediated by effects of the placenta on birth size.

Specific Aim 4: To investigate the role of genetic variation on placental size and shape. DNA was extracted from mothers and offspring in the parent study. The following null hypotheses will be tested:

4A. Genetic variation does not explain variation in placental size and shape.

4B. Interactions between genes and the selected maternal factors (BMI, weight gain, diet) do not explain additional variations in placental size or shape.

Specific Aim 5: To develop and validate a placental index to identify offspring at risk for adverse outcomes with regard to adiposity, vascular function, and metabolic function.

Date proposal received: 
Tuesday, 9 May, 2006
Date proposal approved: 
Tuesday, 9 May, 2006
Keywords: 
Growth, Placenta
Primary keyword: 

B372 - TwinsUk Cohort - Proposal for GWAS of 500 Female Non-identical Adult Twin Pairs - 05/05/2006

B number: 
B372
Principal applicant name: 
Prof Tim Spector (King's College London, UK)
Co-applicants: 
Title of project: 
TwinsUk Cohort - Proposal for GWAS of 500 Female Non-identical Adult Twin Pairs.
Proposal summary: 

Using the twin resource - our scientific program is directed at identifying quantitative trait loci (QTLs) for important biomedical traits relevant to common complex disease including cardiovascular, respiratory and bone diseases. We have been working towards this goal for the past 15 years with substantial success [Spector, 2006 #2; Wilson, 2006 #5; Reneland, 2005 #14; Valdes, 2006 #1; Hammond, 2004 #19]. However, with the completion of the human genome sequence and technological advances in the genotyping, we are now seeking to accelerate this scientific discovery process and shorten timelines for productivity. Our objective in this project is to use individual genotyping and genome-wide association studies (GWAS) in a family-based cohort (twins) with multiple intermediate phenotypes to uncover novel susceptibility genes, explore gene-gene and gene-environment interactions and advance understanding about gene networks which influence disease susceptibility. The current plan will use unique data from the twins in conjunction with other adult population cohorts, which are being genotyped by Sanger (1958BC and Ely Epic study) to provide replication datasets with overlapping phenotypes. We will also compare results with overlapping phenotypes in children to explore age-gene interactions in a study which may be run in parallel (Alspac study).

The specific project aim is to use existing DNA from a sub-cohort of heavily phenotyped 1,000 dizygous (DZ) twins to perform individual genotyping using 250k Illunina Bead Chip Array. We will then conduct a genome-wide association analysis of this data using both total association and family-based statistics to test for associations with extensive existing phenotype and environmental data (i.e. greater than 1000 phenotypes) we have collected over the past 15 years GWAS projects survey common genetic variation by testing a dense set of single nucleotide polymorphisms (SNP) across the genome and we expect this will be an efficient method to uncover novel genes, gene-gene interactions and gene-environment interactions that are relevant to common chronic diseases.

Date proposal received: 
Friday, 5 May, 2006
Date proposal approved: 
Friday, 5 May, 2006
Keywords: 
Genetics, GWAS, Twins, Cross Cohort Study
Primary keyword: 

B353 - To determine the factors including weaning practices that influence the development of clinical allergy or tolerance to food proteins in infants - 04/05/2006

B number: 
B353
Principal applicant name: 
Dr Pauline Emmett (University of Bristol, UK)
Co-applicants: 
A Harding (Not used 0, Not used 0), Dr Kate Northstone (University of Bristol, UK)
Title of project: 
To determine the factors, including weaning practices, that influence the development of clinical allergy or tolerance to food proteins in infants.
Proposal summary: 

(No outline received).

Date proposal received: 
Thursday, 4 May, 2006
Date proposal approved: 
Thursday, 4 May, 2006
Keywords: 
Diet, Respiratory, Allergy, Atopy
Primary keyword: 

B362 - Autism and Cysteine Dioxygenase Gene - 03/05/2006

B number: 
B362
Principal applicant name: 
Dr Rosemary Waring (Retired) (University of Bristol, UK)
Co-applicants: 
Title of project: 
Autism and Cysteine Dioxygenase Gene.
Proposal summary: 

(No outline received).

Date proposal received: 
Wednesday, 3 May, 2006
Date proposal approved: 
Wednesday, 3 May, 2006
Keywords: 
Autism, Genetics, Genes
Primary keyword: 

B367 - Hyperactivity and ADHD in ALSPAC - 01/05/2006

B number: 
B367
Principal applicant name: 
A J Allen (Not used 0, Not used 0)
Co-applicants: 
R Deane (Not used 0, Not used 0), Prof Jean Golding (University of Bristol, UK), S Kirkwood (Not used 0, Not used 0)
Title of project: 
Hyperactivity and ADHD in ALSPAC.
Proposal summary: 

(No outline received).

Date proposal received: 
Monday, 1 May, 2006
Date proposal approved: 
Monday, 1 May, 2006
Keywords: 
ADHD, Antisocial Behaviour
Primary keyword: 

B354 - Determining factors including weaning practices that influence the development of clinical allergy or intolerance to food proteins in infants - 28/04/2006

B number: 
B354
Principal applicant name: 
Dr Pauline Emmett (University of Bristol, UK)
Co-applicants: 
Title of project: 
Determining factors, including weaning practices, that influence the development of clinical allergy or intolerance to food proteins in infants.
Proposal summary: 

(No outline received).

Date proposal received: 
Friday, 28 April, 2006
Date proposal approved: 
Friday, 28 April, 2006
Keywords: 
Respiratory, Allergy, Atopy, Diet
Primary keyword: 

B348 - The Economics of Social Networks their Evolution Economic Function and Dynamic Implications - 24/04/2006

B number: 
B348
Principal applicant name: 
Prof Simon Burgess (University of Bristol, UK)
Co-applicants: 
Prof Paul Grout (University of Bristol, UK), Prof In-Uck Park (University of Bristol, UK), Prof Sarah Smith (University of Bristol, UK)
Title of project: 
The Economics of Social Networks: their Evolution, Economic Function and Dynamic Implications.
Proposal summary: 

Social networks are pervasive. Diverse examples range from friendship groups, neighbourhoods, and the decisions of companies over whom they conduct business with, to more formal networks such as workplaces, political groupings, local voluntary organisations, and international trade organisations. Analysing the formation and evolution of networks is complex and important.

* It is complex because there are two inter-related processes taking place. On one hand, the value any one individual or company gets from belonging to the network, their commitment to it, and the ethos and effectiveness of the network depend crucially on other members of the network. But, at the same time, these factors also influence how the membership changes over time. This complex relationship and feedback provides a rich diversity of potential outcomes and dynamics, not all of which are economically or socially beneficial.

* It is important because networks have important effects on educational outcomes, on employment levels, on social unrest, on how industries grow and decline, etc., and ultimately, through these effects, on the strength of the economy and society. Social networks have been widely studied in a sociological context, but it is only in recent years that the study of such networks has started to affect the way that we think of economic behaviour and the dynamic processes in society and economies. Both theoretical and empirical work in this area is difficult but recent developments in theory and newly available datasets make this possible. This is a new and exciting research agenda, which can provide insights into the importance of collective behaviour and collective norms for economic outcomes, and therefore on the growth of the economy. CMPO has already contributed to this agenda through its work in two distinct areas - corporate culture and neighbourhoods - and, building on this work, we are in a position to make a major contribution to this new field. It is clear from our work and our reading of the other research in this area that this emerging field of study could be pushed forward by a two pronged approach that undertakes (a) theoretical analysis that recognises that the existing

apparently diverse research is really one big issue, and (b) empirical analysis of the development, dynamics and consequences of critical social networks.

Our aim is to undertake a major study with two core, linked, components:

* Theoretical analysis of economic and social networks and communities, and of how different networks interact. The objective is to provide a global analysis that can be used to give deeper insight into specific types of networks. This will build on existing work that is currently based on three distinct but interrelated themes: (i) individual actions based on complementarities, (ii) group formation to achieve group objectives, and (iii) research that focuses on linkages between members.

* A series of econometric studies on large datasets and case studies to test the theories in specific contexts. The topics include (i) the long run implications of patent commons (open-sourced communities where firms share patents), (ii) the transition at retirement from work-based networks to social-based networks, (iii) how workplace networks affect career concerns and career paths, (iv) what is the impact of neighbourhood and peer groups in school on educational outcomes, (v) what is the impact of networks and neighbourhood on productivity and employment, (vi) when and with whom do lasting friendships form among teenagers and how these friendship networks influence educational attainment and criminal or anti-social behaviour.These projects will build on our experience of developing theory alongside empirical analysis, and exploit the skills and the large datasets we have built up over the past 7 years.

Date proposal received: 
Monday, 24 April, 2006
Date proposal approved: 
Monday, 24 April, 2006
Keywords: 
Economics, Stress, Social Conditions, Social Networks
Primary keyword: 

B346 - Depression and Anxiety in Men During and After Pregnancy - 21/04/2006

B number: 
B346
Principal applicant name: 
Dr Jonathan Evans (University of Bristol, UK)
Co-applicants: 
Dr Tom O'Connor (University of Rochester Medical Centre, USA), Dr Paul Ramchandani (Imperial College London, UK), Prof Alan Stein (University of Oxford, UK), Prof Lynne Murray (University of Reading, UK)
Title of project: 
Depression and Anxiety in Men During and After Pregnancy.
Proposal summary: 

The study of depression in women in the perinatal period has led to increased understanding about the course, causes and potential points of intervention and screening. The importance of, for example, post-natal depression in women is now well recognised, both in terms of its effect on maternal health and on children's development. There is growing evidence that the perinatal period is also a point of increased risk for men, and constitutes a public health concern. For example, research to date suggests that men are also affected by the birth of their child, and previous work by this team has shown that depression in men is associated with an increased risk of behavioural and emotional problems in their children. A novel feature of this research is that it examines an under-appreciated health concern in men, depression and anxiety, in a transition period of increased strain. There is ample evidence, for instance, that the transition to parenthood is associated with a marked decrease in marital quality, but little of that work incorporates the findings from perinatal psychiatry. An improved understanding of mood and anxiety changes in men in the perinatal period is important in its own right and will increase our understanding of the dynamics of mental disorder between partners in a period of increased normative stress. This will enable us to improve our prediction and assessment targeting of families at risk for individual, couple, and family disturbance.

Date proposal received: 
Friday, 21 April, 2006
Date proposal approved: 
Friday, 21 April, 2006
Keywords: 
Depression, Mental Health, Pregnancy, Fathers
Primary keyword: 

B350 - Mini-Satellite Mutations in Parents of Children with Cancer Follow-on from A85 - 20/04/2006

B number: 
B350
Principal applicant name: 
Dr Graham Malcolm Taylor (University of Manchester, UK)
Co-applicants: 
Mr Anthony Oojageer (University of Manchester, UK), Mr Marcin Cieslak (University of Manchester, UK)
Title of project: 
Mini-Satellite Mutations in Parents of Children with Cancer Follow-on from A85.
Proposal summary: 

We previously received DNA samples from 110 ALSPAC family trios to determine the frequency of germline minisatellite mutations. These were screened for mutations in the CEB1 minisatellite locus and genotypes obtained from 60 families. Following modification of the genotyping method the family trios were re-screened, and genotypes were obtained from 52 families. In a significant number of cases (n=50), no amplification from at least 1 family member prevented us from obtaining a genotype. We belive that this was due to an insufficient amount of DNA. We now wish to assemble a set of genotypes from 200 ALSPAC families. Although DNA from blood samples would be preferable, DNA from LCL might suffice as long as we can establish that a "germline" mutation is not in fact a somatic mutation caused by the establishment of the cell line. We are thus requesting DNA from 148 families, which could include material from the 50 families that originally failed to amplify. In addition, we would like to test samples derived from LCL made from 20 of the 52 genotyped families, so that we can check that the genotypes are the same. In all therefore, we are requesting DNA from 168 family trios, either from LCL or native DNA.

Date proposal received: 
Thursday, 20 April, 2006
Date proposal approved: 
Thursday, 20 April, 2006
Keywords: 
Cancer, Genetics
Primary keyword: 

B345 - Neurodevelopmental Disorders - DNA Access- Netherlands - 13/04/2006

B number: 
B345
Principal applicant name: 
Dr Gerard Martens (Radboud University, EU)
Co-applicants: 
Title of project: 
Neurodevelopmental Disorders - DNA Access- Netherlands.
Proposal summary: 

(No outline received).

Date proposal received: 
Thursday, 13 April, 2006
Date proposal approved: 
Thursday, 13 April, 2006
Keywords: 
Autism, DNA, Genetics, Motor Co-ordination, Neurology, Vision, Dyslexia
Primary keyword: 

B344 - Environment and Injury Outcomes - 13/04/2006

B number: 
B344
Principal applicant name: 
Dr Lisa DeRoo (National Institutes of Health, USA)
Co-applicants: 
Dr Andres Villaveces (University of North Carolina, USA)
Title of project: 
Environment and Injury Outcomes.
Proposal summary: 

(No outline received).

Date proposal received: 
Thursday, 13 April, 2006
Date proposal approved: 
Thursday, 13 April, 2006
Keywords: 
Environment, Injury
Primary keyword: 

B333 - Vitamin D Pilot Study - 10/04/2006

B number: 
B333
Principal applicant name: 
Dr Barbara Boucher (Barts and London School of Medicine, UK)
Co-applicants: 
Dr Jon Tobias (University of Bristol, UK)
Title of project: 
Vitamin D Pilot Study.
Proposal summary: 

(No outline received).

Date proposal received: 
Monday, 10 April, 2006
Date proposal approved: 
Monday, 10 April, 2006
Keywords: 
Biological Samples, DNA, Vitamin D
Primary keyword: 

B352 - Vitamin D and CYP72B1 - 07/04/2006

B number: 
B352
Principal applicant name: 
Dr John Todd (University of Cambridge, UK)
Co-applicants: 
Title of project: 
Vitamin D and CYP72B1.
Proposal summary: 

(No outline received).

Date proposal received: 
Friday, 7 April, 2006
Date proposal approved: 
Friday, 7 April, 2006
Keywords: 
Genetics, Vitamin D
Primary keyword: 

B359 - Pilot Record Linkage Study Investigating Feasibility of Linking ALSPAC with Avon General Practice Registration System Exeter System and Retrieving Information from General Practice - 01/04/2006

B number: 
B359
Principal applicant name: 
Prof Matt Hickman (University of Bristol, UK)
Co-applicants: 
Title of project: 
Pilot Record Linkage Study: Investigating Feasibility of Linking ALSPAC with Avon General Practice Registration System (Exeter System) and Retrieving Information from General Practice.
Proposal summary: 

Ongoing ALSPAC clinic based data collection is impractical and not cost-effective. Alternative methods of ensuring and extending follow-up are required. Efficient and effective follow-up of the health status (and some other factors) of ALSPAC can be achieved through record linkage. 90% of health service contacts occur in primary care and primary care information systems record all significant clinical diagnoses and events throughout the life course such as hospital visits and admissions and data quality is improving. Projects based on "e health" supported by MRC and NIH are being developed in order to facilitate recruitment and follow-up of patients through primary care information systems (see http://www.pcpoh.bham.ac.uk/ primarycare/mdm/e-health.htm).

Information systems also are being developed regionally to enable Primary Care Trusts and Strategic Health Authorities to communicate and retrieve data from general practice information systems. Avon Information Management and Technology (Avon IMT), based in Bristol (http://nww.avon.nhs.uk/imtconsortium/Information_Services), administers the Exeter system which records details on all patients registered with GPs in Avon, has linked the Exeter system with Hospital Episode Statistics, and is commissioning a new information system to allow remote data retrieval from GP systems. The flagging and record linkage between ALSPAC and Avon Exeter systems is achievable - time and permission allowing. Confidentiality and data security are critical to the development of these new information systems linking and extracting data from primary care. Informed consent is required to allow access to the systems, and to allow ALSPAC to periodically update and follow-up health status of its cohort.

Date proposal received: 
Saturday, 1 April, 2006
Date proposal approved: 
Saturday, 1 April, 2006
Keywords: 
Data Linkage
Primary keyword: 

B332 - Impact of Size at Birth and Early Childhood Growth Patterns on the Microvasculature the Avon Longitudinal Study of Parents and Children ALSPAC - 29/03/2006

B number: 
B332
Principal applicant name: 
Prof Nishi Chaturvedi (Imperial College London, UK)
Co-applicants: 
Prof Robyn Tapp (Imperial College London, UK)
Title of project: 
Impact of Size at Birth and Early Childhood Growth Patterns on the Microvasculature: the Avon Longitudinal Study of Parents and Children (ALSPAC).
Proposal summary: 

It is clear that early life events influence subsequent risk of cardiovascular disease, but the mechanisms involved remain obscure. This proposal will investigate the impact of low birth weight and postnatal growth patterns on the microvasculature of the retina in a birth cohort of children followed over the first 12 years of life. Measurements of retinal microvascular abnormalities will be made using digitally acquired retinal images analysed by an extensively validated semi-automated analysis system. The results of this study will provide novel insights into possible mechanisms linking early life events with future risk of hypertension, cardiovascular disease and diabetes and may contribute to development of appropriate early treatment and intervention

Date proposal received: 
Wednesday, 29 March, 2006
Date proposal approved: 
Wednesday, 29 March, 2006
Keywords: 
Growth, Birth weight
Primary keyword: 

B341 - Preapplication for NIH Interdisciplinary Consortium Grant Toward a Developmental Science of Health Neurons to Neighbourhoods - 29/03/2006

B number: 
B341
Principal applicant name: 
Dr Leon Feinstein (Institute of Education, University of London, UK)
Co-applicants: 
D Keating (Not used 0, Not used 0)
Title of project: 
Preapplication for NIH Interdisciplinary Consortium Grant Toward a Developmental Science of Health: Neurons to Neighbourhoods.
Proposal summary: 

(No outline received).

Date proposal received: 
Wednesday, 29 March, 2006
Date proposal approved: 
Wednesday, 29 March, 2006
Keywords: 
Social Science, Stress, Social Conditions, Miscellaneous
Primary keyword: 

B330 - Dietary Patterns and Risk of Adverse Pregnancy Outcome - 24/03/2006

B number: 
B330
Principal applicant name: 
Dr Pauline Emmett (University of Bristol, UK)
Co-applicants: 
Dr Jean Kerver (Michigan State University, USA)
Title of project: 
Dietary Patterns and Risk of Adverse Pregnancy Outcome.
Proposal summary: 

(No outline received).

Date proposal received: 
Friday, 24 March, 2006
Date proposal approved: 
Friday, 24 March, 2006
Keywords: 
Diet, Pregnancy, Eating disorders, Obstetrics
Primary keyword: 

B331 - Road Traffic Accident Analyses - 23/03/2006

B number: 
B331
Principal applicant name: 
Prof Elizabeth Towner (University of the West of England (UWE), Bristol)
Co-applicants: 
Title of project: 
Road Traffic Accident Analyses
Proposal summary: 

Accidents in the road environment are the commonest cause of death and serious injury in adolescence. Use of transport to and from school and during leisure activities is an important measure of road accident risk, and also provides useful data for assessing the amount of exercise taken by young people. ALSPAC has collected data on accidental injury throughout childhood, and specifically road use and travel to school questions were asked at 13 yrs. We propose to repeat these road use questions at 16 yrs, and add relevant questions about pre- driver attitudes.

Date proposal received: 
Thursday, 23 March, 2006
Date proposal approved: 
Thursday, 23 March, 2006
Keywords: 
Injury
Primary keyword: 

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