Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

Critical gap estimation by numerical and statistical highest likelihood search

Many traffic situations require drivers to cross or merge into a stream having higher priority. Gap acceptance theory enables us to model such processes to analyse traffic operation. This discussion demonstrated that numerical search fine tuned by statistical analysis can be used to determine the most likely critical gap for a sample of drivers, based on their largest rejected gap and accepted gap. This method shares some common features with the Maximum Likelihood Estimation technique (Troutbeck 1992) but lends itself well to contemporary analysis tools such as spreadsheet and is particularly analytically transparent. This method is considered not to bias estimation of critical gap due to very small rejected gaps or very large rejected gaps. However, it requires a sufficiently large sample that there is reasonable representation of largest rejected gap/accepted gap pairs within a fairly narrow highest likelihood search band.

Consumers’ intentions to adopt 3G in regional cities in China : a comparative study

Rapid mobile technological evolution and the large economic stake in commercial development of mobile technological innovation make it necessary to understand consumers' motivations towards the latest advanced and updated technologies and services. 3G (the third generation of mobile communication technology) recently started its commercial development in the world‘s largest mobile communication market, China, after being delayed for a few years. Although China fell behind in commercially developing 3G, it is difficult to ignore studying this area, given the size of the market and promising future developments. This market deserves focused research attention, especially in terms of consumer behaviour towards the adoption of mobile technological innovation. Thus, the program of research in this thesis was designed to investigate how Chinese consumers respond to the use of this newly launched mobile technological innovation, with a focus on what factors affect their 3G adoption intentions. It aimed to yield important insights into Chinese consumers‘ innovation adoption behaviours and to contribute to marketing and innovation adoption research. Furthermore, it has been documented that Chinese consumers vary widely between regions in dialect, lifestyle, culture, purchasing power and consumption attitudes. Based on economic development and local culture, China can be divided geographically into distinctive regional consumer markets. Consequently, the results of consumer behaviour research in one region may not necessarily be extrapolated to other regions. In order to better understand Chinese consumers, the disparities between regions should not be overlooked. Therefore, another objective of this program of research was to examine regional variances in consumers' innovation adoption, specifically to identify the similarities and differences in factors influencing 3G adoption, contributing to intra-cultural studies. An extensive literature review identified two gaps: current China-based innovation adoption research studies are limited in providing adequate prediction and explanation of Chinese consumers' intentions to adopt 3G; and there was limited knowledge about the differences between regional Chinese consumers in innovation adoption. Two research questions therefore were developed to address these gaps: 1) What factors influence Chinese consumers' intentions to adopt 3G? 2) How do Chinese consumers differ between regional markets in the relative influence of the factors in determining their intentions to adopt 3G? In accordance with postpositivist research philosophy, two studies were designed to answer the research questions, using mixed methods. To meet the research objectives, the two studies were both conducted in three regional cities, namely Beijing, Shanghai and Wuhan, centred in the three regions of North China, East China and Central China respectively, with sufficient cultural and economical regional variances. Study One was an exploratory study with qualitative research methods. It involved 45 in-depth interviews in the three research cities to gain rich insights into the research context from natural settings. Eight important concepts related to 3G adoption were generated from analysis of the interview data, namely utilitarian expectation, hedonic expectation, status gains, status loss avoidance, normative influence, external influence, cost and quality concern. The concepts of social loss avoidance and quality concern were two unique findings, whereas the other concepts were similar to the findings in Western innovation adoption studies. Moreover, variances in 3G adoption between three groups of regional consumers were also identified, focusing on the perceptions of two concepts, namely status gains and normative influence. The conceptual research model was then developed incorporating the eight concepts plus the dependent variable of adoption intention. The hypothesized relationships between the nine constructs and hypotheses about the differences between regional consumers in 3G adoption were informed by the findings of Study One and the literature reviewed. Study Two was a quantitative study involving a web-based survey and statistical analysis procedure. The web-based survey attracted 800 residents from the three research cities, 270 from Beijing, 265 from Shanghai and 265 from Wuhan. They comprised three research samples for this study and consequently three sets of data were obtained. The data was analysed by Structural Equation Modelling together with Multi-group Analysis. The analysis confirmed that the concepts generated in Study One were influential factors affecting Chinese consumers' 3G adoption intention, with the exception of the concept external influence. Differences were found between the samples in the three research cities in the effect of hedonic expectation, status gains, status loss avoidance and normative influence on 3G adoption intention. The two Studies undertaken in this thesis contributed a better understanding of Chinese consumers' intentions to adopt advanced mobile technological innovation, namely 3G, in three regional markets. This knowledge contributes to innovation adoption and intra-cultural research, as well as consumer behaviour theory. It is also able to inform international and domestic telecommunication companies to develop and deliver more effective marketing strategies across Chinese regional markets. Limitations in the research were identified in terms of the sampling techniques used and the design of the two Studies. Future research was suggested in other Chinese regional markets and into consumer adoption of other types of mobile technological innovations.

Development of a sewerage infrastructure buffer assessment tool for local authorities

Urban expansion continues to encroach on existing or newly implemented sewerage infrastructure. In this context, legislation and guidelines, both national and international, provide limited direction to the amenity allocation of appropriate buffering distances for land use planners and infrastructure providers. A review of published literature suggests the dominant influences include topography, wind speed and direction, temperature, humidity, existing land uses and vegetation profiles. A statistical criteria review of these factors against six years of sewerage odour complaint data was undertaken to ascertain their influence and a complaint severity hierarchy was established. These hierarchical results suggested the main criteria were: topographical location, elevation relative to the odour source and wind speed. Establishing a justifiable criterion for buffer zone allocations will assist in analytically determining a basis for buffer separations and will assist planners and infrastructure designers in assessing lower impact sewerage infrastructure locations.

Oscillatory regulation of Hes1: Discrete stochastic delay modelling and simulation

Discrete stochastic simulations are a powerful tool for understanding the dynamics of chemical kinetics when there are small-to-moderate numbers of certain molecular species. In this paper we introduce delays into the stochastic simulation algorithm, thus mimicking delays associated with transcription and translation. We then show that this process may well explain more faithfully than continuous deterministic models the observed sustained oscillations in expression levels of hes1 mRNA and Hes1 protein.

The impact of nonlinear exposure risk relationships on seasonal time series data: modelling danish neonatal birth anthropometric data

Background Birth weight and length have seasonal fluctuations. Previous analyses of birth weight by latitude effects identified seemingly contradictory results, showing both 6 and 12 monthly periodicities in weight. The aims of this paper are twofold: (a) to explore seasonal patterns in a large, Danish Medical Birth Register, and (b) to explore models based on seasonal exposures and a non-linear exposure-risk relationship. Methods Birth weight and birth lengths on over 1.5 million Danish singleton, live births were examined for seasonality. We modelled seasonal patterns based on linear, U- and J-shaped exposure-risk relationships. We then added an extra layer of complexity by modelling weighted population-based exposure patterns. Results The Danish data showed clear seasonal fluctuations for both birth weight and birth length. A bimodal model best fits the data, however the amplitude of the 6 and 12 month peaks changed over time. In the modelling exercises, U- and J-shaped exposure-risk relationships generate time series with both 6 and 12 month periodicities. Changing the weightings of the population exposure risks result in unexpected properties. A J-shaped exposure-risk relationship with a diminishing population exposure over time fitted the observed seasonal pattern in the Danish birth weight data. Conclusion In keeping with many other studies, Danish birth anthropometric data show complex and shifting seasonal patterns. We speculate that annual periodicities with non-linear exposure-risk models may underlie these findings. Understanding the nature of seasonal fluctuations can help generate candidate exposures.