Proposal summaries
B17 - Alcohol use during pregnancy child development at 7 years and the influence of genotype on association - 01/07/2001
(No outline received).
B16 - Antibiotic resistance - 01/07/2001
(No outline received).
B15 - The genetic environmental aetiology of anxiety in mothers - 01/07/2001
(No outline received).
B14 - A comparison of parental questionnaires and a system of professional child health surveillance in identifying developmental impairments - 01/07/2001
This project will investigate how well parents and health professionals can identify developmental problems in preschool children, using the ALSPAC study, a total birth cohort of 14,138 children born in 1991-2.
We will test whether parents are the first to identify impairments in their children and whether questionnaires can be an effective method of selecting children for further professional assessment in the pre-school period.
B12 - Vegetarian diet and health - 01/07/2001
(No outline received).
B11 - The ALSPAC cell lines - 01/07/2001
The overall aim of this grant was to create a Lymphoblastoid Cell Line (LCL) collection from children and parents participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). The study has collected data on a scale and with a richness unprecedented in the field of epidemiological study and the generation of the cell line bank would provide material for further genetic, gene expression and metabolomic research.
Development of the resource initially involved establishing a cell culture facility with robotic cell maintenance systems, development of a bespoke Laboratory Information Management System (LIMS) and development of protocols for the transformation and growth of LCLs. Once these systems were in place LCL production would become a routine laboratory procedure enabling cell lines to be produced from all cohort members who consented to cell line production.
B10 - Blood pressure central obesity and insulin sensitivity in early childhood - associated with adrenal function birthweight and early growth - 01/07/2001
At UCLH we run a nationally used service for investigation of adrenal disease based on urine steroid analysis. We frequently get referred samples from children with early pubertal development which we attribute to adrenarche. From epidemiological studies we have conducted in collaboration with Professor Baker in Southampton we have examined changes in adrenal function in 9 year old children in Salisbury. In 24 hour urine collections both adrenal androgen and cortisol metabolites were quantified. Urinary androgen excretion was higher in children who had been light at birth. A 1 kg decrease in birthweight was associated with a 40% increase in androgen excretion. In contrast the relationship with urinary cortisol excretion was U-shaped with higher outputs at the extremes of birthweight. Birthweight was associated with metabolite output independent of current weight, gender and gestational age at birth, indicating that the HPA function was related to fetal growth rather than prematurity. A reduced birth size has also been associated with cardiovascular disease risk and insulin-dependent diabetes. High blood pressure and cardiac hypertrophy may be the consequence of the hyperactive adrenal secreting both cortisol and adrenal androgens from early puberty.
In children with asthma at 8 years of age there is absence of adrenal androgen output. This leads to a reduction in growth rate such that asthmatic children at this stage are shorter than their peers. As they go into puberty they catch-up on the lost height. Loss of adrenal androgens is a feature of many sytemic illnesses (severe burns, HIV and AIDS) and may be linked with states of immune suppression. Children with diabetes would be another group worth investigating.
In keeping with the objectives of the ALSPAC study these children would be worth studying in the same way with the aim of clarifying:
* Adrenal function in relation to birth weight
* Adrenal function in relation to parental adrenal function
* Adrenal function in asthmatic children
In addition to examining the balance of adrenal androgens and cortisol the urine data can be examined to establish whether changes would be due to increased circulating levels or due to changes in the degradative process for cortisol through it's metabolism to inactive cortisone. Thus metabolites of cortisol and cortisone will be examined along with the excretion rates of the free hormones themselves.
24 hour urine samples would be desirable from the children and their parents in order to assess cortisol and adrenal androgen productions.
B279 - ALSPAC data of particular relevance to economists previously A24 - 01/07/2001
(No outline received).
B3 - An investigation into environmental influences on skeletal mineralisation during childhood - 01/06/2001
This project aimed to examine whether skeletal development in childhood is programmed by early life factors, by studying the relationship between maternal diet as assessed by food frequency questionnaire (FFQ), other determinants of maternal nutrition such as smoking and exercise, and bone mass acquisition in childhood. The latter was assessed by measuring total body bone mineral content (BMC), bone area and bone mineral density (BMD) by performing total body DXA scans in 7000 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort at age nine. Regional development at sites such as the spine, upper and lower limbs was also evaluated. In further studies, we aimed to explore the mechanisms involved in any such programming effect by examining the role of genetic factors by studying associations between DXA parameters and single nucleotide polymorphisms (SNPs) in different genes.
B106 - Mannose binding lectin genotype and preterm labour and delivery - 01/06/2001
(No outline received).
B7 - Hearing - 01/06/2001
(No proposal form received).
B6 - Proximity to overhead power lines and depression - 01/06/2001
(No proposal form received).
B5 - Thiomersal in DTP immunisations and long term development of this child - 01/06/2001
N/A
B13 - Lifestyle and changes in body composition through puberty a resource for a study of gene-environment interactions - 01/01/2001
Our proposal was to create a resource for the study of lifestyle and body composition through puberty bycollecting and calibrating data on diet, activity and body composition within the Avon Longitudinal Study ofParents and Children (ALSPAC). The specific aims of the proposal were to:
- Code dietary diaries collected at age 10+
- Code activity diaries collected at age 10+
- Perform total body dual energy X-ray absorptiometry (DXA) scans at age 11+
- Perform calibration studies using magnetic resonance imaging (MRI) and deuterium dilution at age 11+
- Collect and code dietary diaries at age 13+
- Collect and code activity diaries at age 13+
- Perform total DXA scans at age at age 13+
- Perform calibration studies using MRI and deuterium dilution at age 13+
- Calibrate the diet diary measures using repeat diaries, overnight urine collection and activity measures at age 13+
B285 - A national DNA control series for genetic case-control studies based on the British 1958 cohort NOT ALSPAC - 01/01/2001
The MRC / Wellcome Trust Expert Working Group on UK Population Biomedical Collections, in their final report dated March 2000 (section 1.9), suggested that there was a need for intensive genotyping of a "panel of controls ... representing various sectors of the UK population ... for comparison of SNP allele and genotype frequencies with case series." This application describes an expeditious and cost-effective approach to the creation of such a DNA control panel, by producing immortalised cell lines and banked DNA from specimens to be collected over the next two years from members of the British 1958 birth cohort. This fieldwork is already funded by the MRC and all biological material thus derived will be managed according to the MRC guidelines for use of human tissue and biological samples in research (1999), except that our MREC-approved consent forms extend only to non-commercial medical research studies of the causes, diagnosis, treatment or outcome of disease. This nationwide sample of adults followed from birth potentially offers much richer phenotypic information than a control group newly recruited in middle age. In particular, there is prospectively collected data on traits and diseases during childhood and adolescence which would be missed by creation of a de novo panel.
B287 - Antisocial behaviour in girls BAT Study - 01/06/2000
Though universally documented, sex differences in antisocial disorders remain poorly understood, and existing theory and evidence couses heavily on males. This proposal outlines an integrated programme of studies - spanning early childhood to the adult years - designed to test psychosocial influences on sex differences, and to provide the basis for a life-course perspective on antisocial behaviour in girls. Building on collaborations with three ongoing UK and US epidemiology/longitudinal studies the programme tests: (i) influences on the emergence of sex differences in early childhood; (ii) contrasting developmental models for the onset and persistance of girls' antisocial behaviour in childhood and adolescence, and for continuities to problems in psychosocial functioning in adult life; and (iii) biological and psychosocial risks for the development of depressive co-morbidity in early adolescence, and for the onset and recurrence of low mood in adult life.
B284 - Stepfamilies single parent families and childrens development and adjustment Sub-study supervised by Judy Dunn Institute of Psychiatry Avon Brothers and Sister Study - 01/01/2000
Children in single-parent and step-families have higher rates of problems in adjustment, education and health than those in non step-families, yet individual dfferences are marked. This programme of research is focused on the issue of which individuals are most vulnerable, to identify significant sources of risk and support in relation to the mental and physical health of children and parents.
B282 - Genetic and environmental influences on the atherogenic phenotype in the young a population based study - 01/01/2000
We have developed techniques to study endothellal function non-invasively in children and young adults. This programme of work will study how genetic and early enviromental factors affect endothellal function and other markers of early arterial disease (such as arterial stiffness) in a large population of pre-pubertal children undergoing long-term follow-up. Long-term follow-up will also show how these arterial changes progress during puberty and when later risk factors such as smoking are enocuntered.
B294 - To assess whether age at onset of puberty is influenced by intrauterine exposure to endocrine disrupting chemicals - 01/01/1999
HSB would like to purchase the data from the University after it has been collected.HSB would like to increase the amount of FY06 funds to increase the number of questionnaires (from 10,700 to 11,800) and the amount of work associated with pulling and shipping biologic samples from the University of Bristol to the NCEH lab for analysis.
In addition to the Tanner Scale questionnaire, from 2005, ALSPAC will supply biological samples; namely 150 maternal bloods, 150 maternal urines and 300 cord blood samples. This will be at an additional cost of $22,728 for 2007; $16,387 for 2008.
Background: The onset of puberty is difficult to ascertain using Tanner stages, which are subjective in nature. Especially when Tanner stages are self-reported by pre-teen children, questions of accuracy arise. The transition into puberty - represented by entry into Tanner Stage 2 - is especially difficult to determine. Since the outward sign of development reflect underlying changes in concentrations of reproductive hormones, an alternative method of detecting progression into puberty is to examine concentrations of relevant hormones. In pre-pubertal boys, testosterone levels are close of 0 nmol/L. It is only with the onset of puberty that blood concentrations rise and a distinctive pattern develops (Albertsson-Wikland 1997).
Purpose: Many of the boys in the study cohort have completed questionnaires indicating that they had reached puberty (Tanner Stage 2 or higher) as early as age 8. Using the blood hormone concentration, we will compare the self-reported pubertal stage to a more objective measure.
Description: We will examine testosterone concentrations measured by University of Bristol in 1000 (in total) previously collected blood samples of boys aged 7 through 10. Costs of this are included in Modified Line 005.
This sole-source contract is for the data collected during 2004 - 2008.
B208 - Regulation of fasting glucose and birthweight the impact of variation in the glucokinase gene - 01/01/1900
Variation in fasting glucose concentration (FPG) is important for human health. In the normal range FPG is associated with risk of type 2 diabetes and ischaemic heart disease independently of obesity. In pregnancy maternal FPG concentration is an important independent determinant of birth weight in non-diabetic mothers. There is evidence that the regulation of FPG has a strong genetic component.
The main regulator of FPG concentration is the enzyme glucokinase. Our preliminary data shows that common variants in the promoter region of the glucokinase gene are associated with FPG and fetal growth. The minor allele at GCK-30, present in 30% of the UK population raises FPG by0.06 mmol/l (0.04-0.11), p = 0.003; and, when present in the mother, birth weight by 64g (25-102), p = 0.001. We have next shown that variation, further upstream (rs3757840) of the gene, and with no obvious functional role, has a similar, but independent effect on FPG.
In this project we propose to test comprehensively the hypothesis that common genetic variation in GCK alters FPG and birth weight. We will use the latest approaches for capturing the important variation across a gene together with DNA resources from 28,799 mother-child pairs. This approach will establish, if our hypothesis is true, a definitive genetic component to the aetiology of normal variation in FPG and birth weight.