Phenotype and genotype effects on the transcriptome in cardiovascular disease - tools to identify candidate genes

Abstract: The overarching purpose of this thesis is to investigate the expression of human genes and how they relate to cardiovascular disease. Consequently, the ultimate goal is to benefit the patients who are suffering from cardiovascular disease. The only way to improve our treatment of disease is by advancing our knowledge about it. Already, this knowledge is vast and expanding and the work presented herein is therefore only a small piece of a very large context of research, all aimed at this same goal. The context is that of the medical and biological science of 2011, at a time when a genomic era of medicine has already been declared several times, but where the actual impact of genomics on medicine is lacking. It is a time when headlines routinely report the identification of the genes for one disease or another, but where it is harder to suggest direct practical uses for these new findings. One suggestion that is hard to dispute, however, is that the findings increase our knowledge of disease and that we should strive to translate them into clinical application. Translational medical research is the catchphrase applied to this suggestion. Since the discovery of the genomic code in the 1960s, it has been known that biological information flows from the genome into practical form and function as proteins. Gene expression is the intermediate of this path and any genomic concept is likely to be mediated through transcription in one way or another. And so, taking cue from the cell itself, the proper subject for translating genomic era findings to the clinical application is to study the products of the genes. The pieces of the puzzle provided by this thesis all concern gene expression and they all concern translation into medical application. Each of the five papers included investigate different aspects of this focus point. One paper investigates the technology for extracting gene expression information (I). Two look from the genome towards the gene expression in order to interpret genomics better (II and III). Another paper looks from disease towards gene expression to seek clues on the mechanism of disease (IV). And finally the last paper observes the gene expression, irrespective of its biological meaning, and asks how much it can tell about the future of a patient (V).