Proposal summaries
B184 - A UK-Singapore cross cohort comparison of the risk factors for myopia - 01/07/2004
(No outline received).
B183 - Impact of a family history of diabetes on early weight gain body composition and fitness - 01/07/2004
(No outline received).
B178 - Risk taking behaviour in adolescence - its origins and consequences - 01/07/2004
(No outline received).
B176 - The natural history of asthma and wheezing illnesses from birth to adolescence determinants of remission of asthma symptoms - 01/07/2004
The proposed project is based on the follow up of a well-characterised population of children in the
Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate factors associated with the onset and
remission of asthma symptoms during adolescence. ALSPAC is a longitudinal birth cohort of 13,971 infants
followed from birth. Detailed analyses of asthma phenotypes have been made on data from early childhood to age
8 1/2 years, including objective measurements of lung function and allergic status. The proposed study will extend
these observations through the critical period of adolescence to study exposures associated with onset or remission
of asthma symptoms and their relationships with further objective outcome measures proposed in this project.
Aims & Objectives: The aims are to describe the natural history of asthma from birth to adolescence and to examine
the factors that influence the remission of asthma symptoms. The primary hypotheses to be tested in this project are
that changes in body fat composition, diet, habitual activity and the uptake of active smoking are independently
associated with the remission, persistence or onset of asthma symptoms during adolescence (from 8 1/2 to 15+ years)
and that effects differ between males and females in this population. We will investigate the possible mechanisms
of these effects by measuring objective outcomes, including lung function, bronchodilator reversibility and a marker
of airway inflammation, exhaled nitric oxide. Finally, we will investigate whether exposures during adolescence
interact with prior exposures and asthma history in determining the resolution of asthma symptoms in adolescence.
Methods: Exposure data will be collected as part of the ALSPAC Core Programme. Data on body composition will
be available from whole body DXA scans repeated at 11, 13+, and 15+ years, reports of physical activity are
available from annual questionnaires and objective measurements of activity have been made using accelerometers.
Dietary intake is calculated from food frequency questionnaires and tobacco smoke exposure will be estimated from
parental and child questionnaires. We will also measure urinary cotinine at 15+ years to validate these reports as
part of this project. Outcomes will include extending the analysis of asthma symptoms from 8 1/2 years to 15+ years
using data from annual self-report questionnaires. From these we will establish asthma trajectories for each child
from birth to adolescence. We will measure lung function by spirometry at 15+ years and measure bronchodilator
reversibility. We will also assess airway inflammation by measuring exhaled nitric oxide (FeNO) at 15+ years.
These measurements will be used to characterise subjects with asthma remission depending on the presence or
absence of airflow obstruction and airway inflammation.
Outcomes: the project will provide novel information on factors associated with asthma remission during the
critical period of adolescence in a large contemporary cohort of children. Knowledge of these factors and their
associations with persistent abnormalities of pulmonary function and/or airway inflammation may help to identify
targets for interventions aimed at encouraging asthma remission. In addition, the data generated by this project will
provide important new data for the study of genetic susceptibilities and gene-environment interactions in the natural
history of asthma during childhood.
B172 - Impact of minor head injury on cognitive emotional behavioural and real life outcomes in childhood - 01/06/2004
(No outline received).
B171 - Investigating the link between sleep duration appetite and obesity - 01/06/2004
(No outline received).
B170 - Point prevalence of nasal carriage of methicillin resistant and methicillin susceptible aureus - 01/06/2004
(No outline received).
B169 - The processing of chromatic signals fundamental studies and clinical applications - 01/06/2004
(No outline received).
B181 - Medically Unexplained Symptoms MUPS - 01/05/2004
(No outline received).
B168 - Smoking initiation - 01/05/2004
(No outline received).
B167 - Fat or big bones Bio-electrical impedance in childhood as a measure of lean and fat mass - 01/05/2004
Obesity in childhood is increasing, and if unchecked, will lead to a new epidemic of heart disease in the future. We need to know when obesity begins and why, but measuring weight cannot distinguish healthy, muscular children from those that who are obese. Bioelectric impedance uses the body's electrical resistance to estimate body fatness, but at present, it is not widely used in childhood, as we know little about what is normal at different ages. We will use measurements from two large studies to define the normal range for lean and fat tissue and find out how these relate to infant feeding, growth and physical fitness.
B166 - Genetic and environmental influences in speech and language development disorder - 01/05/2004
(No outline received).
B165 - PTHR1 - Investigation of the link between calcium homeostasis in utero and skeletal development - 01/05/2004
(No outline received).
B161 - An investigation of genetic epidemiological risk factors for psychotic-like symptoms in adolescent birth cohort - 01/04/2004
Objective: Toexamine genetic and environmental risk factors for developing sub-clinical, psychosis-like symptoms (PLIKS) during adolescence. Specifically:
1. To investigate whether genetic variation within NRG1, DTNBP1, DAAO, G72, RGS4 and CHRNA7 are associated with PLIKS.
2. To investigate whether cannabis or tobacco alter risk of PLIKS.
3. To examine the interplay between genetic variation and cannabis or tobacco exposure on risk of PLIKS, as well as the interplay with other risk factors for schizophrenia, including markers of neurodevelopmental abnormalities.
Background:Approximately 15% of the population report psychotic-like experiences not meeting criteria for clinical disorders. These occur more commonly than schizophrenia, and are likely to be closer to underlying aetiological pathways. Studies of PLIKS may increase understanding of schizophrenia aetiology, and help focus prevention and intervention strategies. All the genes above, as well as cannabis and tobacco, are thought to effect glutamatergic transmission. Examination of gene-environment interplay may provide further insights into aetiological mechanisms.
Design: Cohort study (nested case-control for genetic associations).
Method: The ALSPAC birth cohort of 14,000 children, currently age 11-12 will be used. Large quantities of data, including DNA, are already available. PLIKS and substance use data were collected at age 11-12 and will be re-collected at 13-14 & 15-16. Outcome to be investigated is risk of PLIKS (quantitative and dichotomous measures). Genetic analyses will include examinationunder different genetic models, haplotype analysis, and family-based association. Regressionmodels will also be used to examine association with cannabis/tobacco usewhilst adjusting for confounders, and for exploratory analysis of gene-environment interplay.
B142 - Environmental personal risk of accidental injury to young children in the home - 01/04/2004
The aim of this proposal is to identify specific individual, psychological and environmental factors associated with child accident involvement, and to examine both their independent and interactive effects on risk-taking and injury in the home environment. The proposed study will examine these effects both cross-sectioally and longitudinally in a contemporary representative sample - the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.
B358 - Genetics of Dyslexia - 01/04/2004
(No outline received).
B159 - Factor V Leiden and adverse pregnancy outcome - 01/03/2004
The aetiology of adverse pregnancy outcomes such as pre-eclampsia and fetal growth retardation is likely to be multifactorial and influenced by a complex interplay between maternal, fetal and placental factors. Given that a successful pregnancy outcome is highly dependent on the establishment and maintenance of an adequate placental circulation, it is possible that abnormalities of placental vasculature, leading to inadequate fetomaternal circulation, may be responsible for at least some poor pregnancy outcomes. This has led to an interest in the thrombophilias as risk factors for adverse pregnancy outcome. The factor V Leiden mutation is the most common form of inherited thrombophilia.1 A point mutation in the factor V gene at nucleotide position 1691, resulting in an arginine to glutamine substitution, reduces the sensitivity of the factor V protein to inactivation by activated protein C (activated protein C resistance) resulting in a pro-coagulant state and an increased risk of thrombosis.2 The trait is inherited in an autosomal dominant manner with the risk of thrombosis increased seven times in heterozygotes and 80 times in homozygotes. 3 Studies have shown that the distribution of the factor V Leiden mutation varies in different populations, being present in about 5% of Caucasian individuals (Europeans, Jews, Arabs and Indians) and virtually absent in Africans and Asians.
Rey et al 2003 published a meta-analysis confirming the association between recurrent fetal loss and the factor V Leiden mutation.4 Rai et al 2002 aimed to tease out the isolated contribution of factor V Leiden by comparing FVL+ women with recurrent fetal loss to FVL- women with the same history of fetal loss. The live birth rate was significantly lower among the women who carried the mutation confirming that factor V Leiden independently increases the risk of fetal loss.5 Data from our recently published meta-analysis concludes that factor V Leiden is also associated with a 2.9 fold (95%CI 2.0-4.3) increased risk of severe pre-eclampsia and a 4.8 fold (95% CI 2.4-9.4) increased risk of fetal growth retardation6.
A function enhancing mutation in the Prothrombin gene (Prothrombin G20210A) results in higher circulating levels of prothrombin, the precursor of thrombin. This mutation is present in 2.3 % of the general population is associated with a 3-4 fold increased risk of thromboembolism. The Leiden thrombophilia study reported a relative risk of 2.8 with the 20210A Prothrombin gene variant in 2.3% of healthy carriers and 6.2% of consecutive controls.
A meta-analysis with pooled data from nine studies (n=2087) indicated a significant association between the prothrombin G20210A mutation with late non-recurrent fetal loss (2.30,1.09-4.87) 4 A number of small case-control studies have conflicting results with respect to a possible association between prothrombin and the risk of pre-eclampsia and intrauterine growth restriction; and larger prospective studies are needed to clarify a possible relationship. There have been no studies evaluating a possible risk of adverse pregnancy outcome associated with the fetal Prothrombin G20210A mutation.
Most of the research in this area has been in the form of case-control studies which are notoriously subject to bias. We are therefore proposing a nested case-control study, which is methodologically more vigorous.
Placental thrombi resulting in placental infarction may occur on either side of the maternal-fetal interface, and theoretically the fetal as well as the maternal factor V Leiden genotype may influence the risk of adverse pregnancy outcome. Therefore, we aim to address the effect, not only of maternal factor V Leiden and prothrombin G20210A mutation, but also of fetal factor V Leiden and prothrombin G20210A mutation on pre-eclampsia, intrauterine growth retardation and late fetal death.
1 Rosendaal F. Thrombosis Series: Venous thrombosis: a multi causal disease. Lancet 1993;353:1167-73.
2 Bertina R, Koelenan B, Koster T, Rosendall FR, Dirven RJ, de Ronde H, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:65-67.
3 Spina V, Aleandri V, Morini F. The impact of Factor V Leiden on pregnacy. Hum Reprod Update 2000;6: 301-306.
4 Rey E, Kahn S, David M, Shier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003; 361:901-908.
5 Rai R, Backos M, Elgaddal S, Shlebak A, Regan L. Factor V leiden and recurrent miscarriage-prospective outcome of untreated pregnancies. Human Reproduction 2002;17:442-445.
6 Dudding TE, Attia J. The association between adverse pregnancy outcomes and maternal factor V ledien genotype: a meta-analysis. Thromb Haemost 2004;91:700-11.
B154 - Selective assessment of colour motion and contrast acuity in the ALSPAC study - 01/03/2004
(No outline received).
B152 - Childhood viral infections - 01/02/2004
(No outline received).
B151 - Are higher levels of physical activity in pregnant women associated with better mental health before and after children - 01/02/2004
(No outline received).