Electronic Thesis and Dissertation Repository


Master of Science




Dr. Robert A. Hegele


Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using both established and novel genomic technologies, including candidate gene resequencing, high-throughput targeted microarray genotyping and candidate variant genotyping. We demonstrate that a private and common variant, p.G116S, within the low-density lipoprotein receptor (LDLR) gene among Inuit descendants has a large effect on plasma cholesterol; that variation in cardio-metabolic and Alzheimer disease (AD) loci is not associated with susceptibility to the pre-dementia phenotype known as “cognitive impairment, no dementia”; and that established type 2 diabetes (T2D) variants are not associated with T2D susceptibility among select aboriginal Canadian and Greenland cohorts. Together, these studies represent a selection of established and novel genomic strategies for the investigation of complex disease genetics which are likely to remain fundamental in the continued investigation of complex disease pathogenesis.