Proposal summaries
B437 - Diet diaries at 17 - 29/11/2006
Purpose
There is growing evidence of the role of specific dietary factors in cancer prevention.
In a large, contemporary group of young people (the ALSPAC cohort), now at the
cusp of adulthood, this study will identify a dietary pattern characterised by these
cancer-protective components and study the antecedent determinants of these
eating habits. This will include the role of socio-economic status, parental attitudes
and behaviours and specific genetic traits, primarily relating to taste perception. It
will also examine the extent of tracking of dietary habits throughout childhood and
adolescence to adulthood. Together this data will inform public health strategies to
encourage the early adoption of a cancer-protective diet.
B434 - Genetic and environmental influences on the link between mood and anxiety problems in childhood and substance use in adolescence - 24/11/2006
Mood and anxiety problems may increase risk of development of alcohol abuse. It is unclear to what extent genetic or environmental risk factors contribute to this relationship. This project will examine the relations between childhood mood and anxiety problems and adolescent alcohol involvement using already existing data from the Avon Longitudinal Study of Parents and Children (ALSPAC). This study includes a wealth of psychological, sociological and genetic data from around 15,000 mothers and their children (who have been followed from birth to 14 years). Analyses will take into account genotypic information (e.g., serotonergic polymorphisms) as well as environmental factors such as the children's family environment.
B435 - Prenatal glucocorticoids hypothalamic-pituitary-adrenal HPA - axix activity and HPA-axis related disorders in children - 23/11/2006
No outline received
B433 - Social inequalities nutrition and obesity in childhood developing an International multi-centre study - 23/11/2006
No outline received
B436 - The association of asthma with hormonal status in adolescents - 22/11/2006
In adult women asthma severity has been associated with phase in menstrual cycle1, reported early menarche2 and pregnancy3. Incident asthma has been associated with the use of hormone replacement therapy4 and with the use of the oral contraceptive (abstract only) with effects being more marked in lean women . These observations suggest that exposure to female sex hormones is important in asthma but the hormonal profile that would explain these associations is far from clear5. Studying children, particularly but not exclusively girls, through puberty may improve our understanding of the disease.
There are few large cohort studies with detailed information on asthma phenotype (eg;symptoms, atopic status and lung function), pubertal stage and other relevant physiological (eg: waist hip ratio; fasting blood sugar) and lifestyle/environmental factors (eg exercise). To date only the Tucson cohort has examined in depth the association of asthma with puberty but these analyses are insufficiently powered to fully disentangle the effects of obesity, age of puberty and differences between boys and girls. In the 1200 children studied analyses have suggested that there is a strong association of new asthma onset6 with increase in BMI - particularly in girls with early menarche - and that there is greater persistence of asthma symptoms through adolescence in those who are obese and in those with early puberty -associations observed in both boys and girls7 and which are independent of each other.
While it is widely thought that the association of asthma with early puberty may reflect a direct effect of hormones on asthma, an alternative hypotheses is that it reflects an underlying association of asthma with the metabolic syndrome. Epidemiological evidence for this is an association of asthma and some atopic markers with menstrual symptoms suggestive of polycystic ovarian syndrome (a feature of metabolic syndrome) 8 and studies suggesting an association of markers of insulin resistance with abnormal lung function9;10
The proposed collaboration would aim to:
1) Describe gender differences in asthma onset and asthma persistence from ages 8 to 15 years
2) Assess the association of age of puberty with asthma onset, asthma persistence, atopy and lung function
3) Develop from these testable hypotheses to explain observed associations. This would lead to a grant application for personnel and possibly further physiological/serological measures (including questionnaire based/physiological measures for the next follow-up). The application would most likely be to Asthma UK where asthma in adolescence has been identified as a priority area for research.
B430 - Bullying data and precursors - 16/11/2006
No outline received
B428 - The nature of the association between alcohol consumation and depression over time an investigation using data on mothers and their partners from in ALSPAC - 16/11/2006
No outline received
B432 - Stress obesity and risk of early breast development and menarche - 15/11/2006
Background:Early life is critical in mammary carcinogenesis and, thus, prevention efforts are increasingly shifting focus to examining youth.Obesity and chronic stress exposures (adverse life events, low socioeconomic status) are independently associated with early pubertal development that increases subsequent breast cancer risk.Specific Aims:In a multiethnic cohort of 443 girls, aged 6-7 at baseline, and followed for 2 years to date: 1. Determine the strength of the associations among chronic stress, visceral fat, early breast development (thelarche) and menarche. 2. Address unresolved questions about potential mediators of the link among chronic stress, visceral adiposity and the timing of thelarche and menarche.Methods:The proposed study builds on an established prospective epidemiological observational study of environmental determinants of puberty and breast cancer risk (n=443) (PI: Dr. Larry Kushi, Kaiser Permanente Northern California), which is a part of the NIH-funded Bay Area Breast Cancer and the Environment Research Center (PI: Dr. Robert Hiatt). Participants are recruited concurrently at sites in Cincinnati and New York, providing an opportunity to expand analyses across sites (N greater than 1200).Implications:The proposed study is poised to advance the field of breast cancer prevention by being the first to longitudinally examine associations among stress, obesity and pubertal timing. The findings of this study will help inform interventions targeting modifiable factors such as physical activity and diet in order to prevent obesity and delay puberty. Such interventions constitute a promising strategy for primary prevention of breast cancer.
B431 - Early child development - emotional regulation - 14/11/2006
No outline received
B429 - DAWBA data on internalising disorders - 14/11/2006
No outline recieved
B439 - Investigation of the role of ESR1 polymorhisms in skeletal development - 10/11/2006
Aims
1. The role of ESR1 rs77757956 in skeletal development
A. We will determine whether the interaction between ESR1rs77757956, TBLH ABMC and puberty in peri-pubertal girls described above results in a lower TBLH ABMC in post-pubertal girls with the TA/AA genotype, but not boys, by analyzing these relationships in approximately 5000 15 year-old children from ALSPAC.Whethercortical bone geometry in post-pubertal girls is also affected will be addressed, by analyzing relationships withpQCT parameters.
B. Whether equivalent relationships between ESR1rs77757956 and skeletal development are observed in other populations will be investigated, by repeating these analyses in a cohort of girls from Finland with repeated DXA and pQCT measures during puberty.
C.We plan to study whetherrs77757956affects peak bone mass in adulthood, by analysing associations with DXA measures in around 3000 mothers from ALSPAC, and 4000 women from the St Thomas' Twin cohort. Further analyses will be performed in these cohorts to examine possible effects of this polymorphism on fracture and obesity risk in adulthood.
D.As a prelude to future functional studies, we will determine whetherrs77757956 influences skeletal phenotypes directly, or as a consequence of linkage with other SNPs,following genotyping of ALSPAC children for the 6 other SNPs with which this is in LD.
2. The role of other ESR1 polymorphisms in skeletal development
We will determine if other ESR1 gene variants influence skeletal development or peak bone mass, by exploring associations between DXA measures and common haplotype-tagging ESR1 SNPs analysed as part of a genome-wide association study (GWAS) in a 10% sub-group of ALSPAC children, and in 4000 women from the St Thomas' Twin cohort. Whether associations can be replicated in other children (remainder of ALSPAC, cohorts of peripubertal girls in Finland and postpubertal boys in Sweden) or adults (ALSPAC mothers) will subsequently be investigated.
3. The influence of ESR1 polymorphisms on ERa expression
We will evaluate the feasibility of using ALSPAC cell lines to examine whether ESR1 genotypes influence ERa expression, by investigating whether maternal/child EBV-transformed B lymphocyte cell lines express ERa mRNA at levels which can be reliably quantitated using the ARCS high throughput method. Further studies will be performed in light of these findings, relating ESR1 genotype to ERa expression levels in cell lines from ALSPAC children
B424 - Analyses of relation of parity to atopy in ALSPAC - 02/11/2006
Background: Childhood allergy and sibship
There is consistent and strong evidence that the prevalence of atopy and hayfever are lower in children from large families or of higher birth orders1. The pattern is less consistent for childhood asthma, probably because its phentoype is less specific and easily confused with infection-related and other forms of non-atopic wheeze.
Sibship size and birth order are inevitably correlated - especially where average families are small - and it is not always easy to examine their independent effects. The apparent protection offered by increasing family size was originally ascribed to variations in the rates of early childhood infection and thus formed the basis for the 'hygiene hypothesis'2. This remains the most plausible and parsimonious explanation for much of the epidemiology of childhood allergy; but it does not preclude additional mechanisms related to birth order. For example, two studies of UK populations, separated in age by about 30 years, were unable to account for birth order effects by examination of recorded infections in early childhood3;4.
Within representative cohorts of families living in Ashford (Kent), Barcelona and Menorca we originally observed, on cross-sectional analysis, that mothers - but not fathers - who have given birth to more children are less often atopic. This relationship was not explained by maternal age5. Subsequently and prospectively, within the Ashford population, we reported that over seven years the loss of maternal atopy and hayfever are associated with a higher number of intervening pregnancies6.
One explanation for these observations is that they reflect changes in maternal and consequently maternal-foetal immunology with successive pregnancies, and that this in turn influences risk of allergic disease in the offspring. If this were the case one might expect to see a relation between parity and cord IgE. The observation that the birth order effect may be stronger if older siblings are male7, could reflect stronger immune responses of the mother to male compared to female foetuses. If maternal-foetal immunology is important, then one might expect a mother's change of partner to influence the birth order effect and for a child with older sibs born to a new father to have the same risk of atopy as a first-born child. This is analogous to the risk of pre-eclampsia which is higher in first than in subsequent pregnancies, but reverts to the risk for primiparous women in later pregnancies if the mother changes partner.
B422 - Social currency and health seeking behaviour - 31/10/2006
No outline received
B420 - Norweigian biobank for human primary teeth - 30/10/2006
30/10/2006
B419 - Conduct disorder at 17 - 30/10/2006
No outline received
B418 - Development of ear drum retractions - 30/10/2006
No outline received
B417 - Disordered eating in adolesence A longitudinal study of risk factors - 30/10/2006
Disordered eating is a common problem in pre-adolescents and adolescents. About 30% to 60% of young girls show disordered eating at some point between the ages of 12 and 18
Abnormal eating patterns such as under-eating and binge eating are associated with a high disease burden (15th among the top 20 causes of disability)
Disordered eating encompasses extreme forms of eating such as the eating disorders (ED), anorexia nervosa (AN), bulimia nervosa (BN), eating-disorders not otherwise specified (EDNOS) including binge eating disorder (BED); and less extreme problematic eating, such as over-eating and under-eating as well as unhealthy weight-control behaviours: self-induced vomiting, laxatives, diet pills, excessive exercise or fasting for weight loss. It affects the physical and mental health of young people, impacts upon school performance and interpersonal relations, and also increases the risk for eating disorders in later life.Eating disorders have the highest mortality rate amongst psychiatric disorders, and the mortality rate associated with anorexia nervosa is 12 times higher than the death rate of all causes of death for females 15 - 24 years old. Moreover, disordered eating might induce long-standing changes in the neurobiological pathways affecting eating behaviours.
The purpose of this study is to identify the risk factors related to the development of disordered eating and to determine risk factors for the persistence of disordered eating during adolescence. This will aid the development of early intervention and preventative strategies for disturbed eating and in so doing have an impact on public health
B416 - TIM data request - 30/10/2006
No profile received
B414 - European Cohort Network EUCCONET - 16/10/2006
No outline received