Proposal summaries
B576 - Dietary patterns in early childhood and IQ - 23/10/2007
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.
B672 - Enviromental determinants of physcial activity - 22/10/2007
B572 - Enviromental determinants of physcial activity - 22/10/2007
B571 - The ontogeny of paranoid delusions - 22/10/2007
No outline received
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
No outline received
B573 - Preterm Birth Whole Genome Association Study - 16/10/2007
No outline received
B569 - Genetic and environmental influences on developmental trajectories of alcohol use misuse and related behaviours - 15/10/2007
No outline received
B574 - Variants in the cannabinoid receptor gene and their influence on alcohol and drug consumption - 10/10/2007
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).
B568 - The influence of the enviroment on face shape - 10/10/2007
No outline received
B592 - Predictive Value of Questionnaire Data for Assessing Atopic Status - 06/10/2007
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.
B567 - How common is CFS/ME at age 13 and what factors increase the risk of developing it - 03/10/2007
No outline received
B566 - An investigation of language-impairment and dyslexia associated SNPs within the general population - 03/10/2007
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.
B561 - Genetic contributions to childhood resilience - 01/10/2007
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.
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
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
B558 - The structure and origins of schizotypal personality traits in adolescence - 01/10/2007
No outline received
B557 - Electronic patient records and database research - 28/09/2007
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.
B560 - Pilot study of ALSPAC hearing data at age 11 work towards grant application - 27/09/2007
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.
B555 - The association between social functioning social cognition and psychosis-like symptoms in the ALSPAC birth cohort - 20/09/2007
Aims
1/ To examine the cross-sectional association between social functioning, as measured by the SCDC at age 13 and the presence of PLIKS at age 13 yrs
2/To examine the strength PLIKS, as measured at age 13, as a predictor of poor social functioning at age 15 years.
3/To examine the role of social cognitive ability, as measured by the Emotion Triangles Test, at age 13, as a mediator, in the above association.
4/To examine how social functioning and social cognition as measured at age 13, predict the future development of PLIKS, as measured by questionnaire at ages 14 and 16 years.
B556 - Relation of adverse psychosocial enviroment to childhood obesity and early puberty as markers of future breast cancer risk - 19/09/2007
Objectives/aims:
- To establish whether markers of adverse psychosocial environment (such as adverse socioeconomic circumstances and stressful life events) are associated with biochemical markers of cortisol metabolism (fasting cortisol levels and urinary excretion of total cortisol metabolites at age 8), central fat patterning (by waist circumference and DXA), and earlier timing of thelarche and menarche (by questionnaire).
- To establish whether these associations are modified by level of physical activity and energy intake.
In addition to providing a test of our proposed stress-body fat-puberty model, the proposed study also has the potential to inform the scientific basis of targeted interventions to reverse the childhood obesity epidemic .
B552 - Meta-analyses of genetic association studies of psychiatric disorders - 17/09/2007
No outline received