Many complex diseases are known to have a substantial genetically heritable component. Elucidation of these genetic risk factors provides increased knowledge of the biological mechanisms that result in the diseases while also presenting new potential targets for therapy. This thesis explores the methodology of mapping genetic loci using isolated populations in the context of quantitative trait analysis. Chapter 1 explores the rational for the project, discussing the benefits of using quantitative traits rather than binary disease status and the pros and cons of using isolated populations. This is followed by a brief history of genetic mapping with reference to type 2 diabetes mellitus (T2D) and related quantitative traits. Chapter 2 introduces the methods used in this thesis. This includes strategies to deal with medication, methods to determine kinship between individuals, linkage analysis, association analysis and meta‐analysis of multiple studies. Chapter 3 presents linkage analysis of T2D related traits carried out in 2 – 4 populations depending on availability of the traits and appropriate marker data. Chapter 4 presents the results of association analysis for T2D related traits in 3 – 5 populations using genome‐wide SNP data. The results using the alternate methods described in chapter 2 are compared using fasting glucose as this was the most widely measured phenotype. Chapter 5 introduces additional traits derived by pulse wave analysis and discusses their relevance to metabolic disease before presenting association analysis using the preferred method from chapter 4. An overall discussion of the strengths and weaknesses of the analysis is given in chapter 6.

This study investigates the links between economic and demographic variables by examining the impact of industrialization on adult mortality in eastern Scotland, c. 1810-61. Using the concept of the urban hierarchy, sixteen parishes in the counties of Angus and Fife were selected to represent different degrees of industrialization. Patterns of adult mortality in these parishes between 1810 and 1854 are then examined using data on burials from the parish registers. The results are checked by comparing them with the results obtained from an analysis of vital registration data on deaths for the period 1855-61. Thus overall trends in adult mortality are identified and then disaggregated by age, sex, cause of death and occupation. The results show that adult mortality was generally higher in the most industrialized areas. Furthermore, rates in these parishes generally increased over the period whilst in the less industrialized areas they fell. Overall most people died from infectious diseases but deaths from these causes (including tuberculosis) fell over the period. The increase in mortality appears to be in part due to a rise in deaths from respiratory diseases (especially amongst textile workers in the main industrial centres) and food- and water-borne illnesses. This suggests that industrialization had a negative impact on adult mortality rates, causing a short-term rise in mortality in the early to mid-nineteenth century. This was in part due to the direct effect industrialization had, with the shift towards textile employment probably leading to increased mortality from respiratory diseases especially amongst factory workers. The impact of industrialization also appears to have operated indirectly via the impetus it gave to urbanization and changes in the spatial distribution of the population that resulted in worsening sanitary conditions and increased exposure to infection.

published_or_final_version / Biological Sciences / Master / Master of Philosophy

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