Abstract
The promise of genomic medicine lies in the ability to identify those factors that modify risk of disease at the individual level and, once identified, to be able to provide a personalized treatment or intervention to ablate the disease process. This concept is based upon a number of assumptions and current limitations that genomic science has yet to address. Critical to the development of personalized medicine is the determination of the genetic and epidemiologic cause of complex human disease, such as coronary heart disease, diabetes, asthma, and stroke. The risk factors that predispose an individual to any one of these disorders may not be unique, and the genomic profiles may be similar. Increasing the complexity of understanding the pathogenesis of these disorders is the growing recognition that the genetic risk factors likely interact not only with each other but also with poorly understood environmental factors. Ultimately, the prediction of an individual’s risk for any disorder will be determined by their genotype and their environmental exposures; however, in the absence of a defined genomic fingerprint, a subset of confirmed genetic risk factors can be used to help define biomarkers of disease. Clinically validated biomarkers can then serve as surrogates for the combined effects of genotype and environment and provide insights into disease pathogenesis.
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References
Collins, F. S., Green, E. D., Guttmacher, A. E., Guyer, M. S. (2003) A vision for the future of genomics research. A blueprint for the genomic era. Nature, 422, 835–847.
The International HapMap Consortium. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature, 449, 851–862.
Evans, D. M., Cardon, L. R. (2004) Guidelines for genotyping in genomewide linkage studies: Single-Nucleotide-Polymorphism maps versus microsatellite maps. American Journal of Human Genetics, 75, 687–692.
Helgadottir, A., Manolescu, A., Thorleifsson, G., Gretarsdottir, S., Jonsdottir, H., Thorsteinsdottir, U., et al. (2004) The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nature Genetics, 36, 233–239.
Hakonarson, H., Thorvaldsson, S., Helgadottir, A., Gudbjartsson, D., Zink, F., Andresdotttir, M. et al. (2005) Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction. Journal of the American Medical Association, 293, 2245–2256.
Meschia, J. F., Brott, T. G., Brown, R. D., Crook, R., Worrall, B. B., Kissela, B., et al. (2005) Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke. Annals of Neurology, 58, 351–361.
Zee, R. Y. L., Cheng, S., Hegener, H. H., Erlich, H. A., Ridker, P. M. (2006) Genetic variants of arachidonate 5-lipoxygenase-activating protein, and risk of incident myocardial infarction and ischemic stroke. A nested case-control approach. Stroke, 37, 2007–2011.
Maznyczka, A., Mangino, M., Whittaker, A., Braund, P., Palmer, T., Tobin, M., (2007) Leukotriene B4 production in healthy subjects carrying variants of the arachidonate 5-lipoxygenase-activating protein gene associated with a risk of myocardial infarction. Clinical Science, 112, 411–416.
Wilson, P. W., D’Agostino, R. B., Levy, D., Berlanger, A. M., Silbershatz, H., Kannel, W. B. (1998) Prediction of coronary heart disease using risk factor categories. Circulation, 97, 1837–1847.
Greenland, P., Knoll, M. D., Stamler, J., Neaton, J. D., Dyer, A. R., Garside, D. B., et al. (2001) Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. Journal of the American Medical Association, 290, 891–897.
Ridker, P. M., Riffai, N., Rose, L., Buring, J. E., Cook, N. R. (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. New England Journal of Medicine, 347, 1557–1565.
Wang, T. J., Gona, P., Larson, M. G., Tofler, G. H., Levy, D., Newton-Cheh, C., et al. (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. New England Journal of Medicine, 355, 2631–2639.
Wellcome Trust Case Control Consortium. (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661–678.
The GAIN Collaborative Research Group. (2007) New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nature Genetics, 39, 1045–1051.
Helgadottir, A., Thorleifsson, G., Manolescu, A., Gretarsdottir, S., Blondal, T., Jonasdottir, A. et al. (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science, 316, 1491–1493.
Samani, N. J., Erdmann, J., Hall, A. S., Hengstenberg, C., Mangino, M., Mayer, B., et al. (2007) Genomewide association analysis of coronary artery disease. New England Journal of Medicine, 357, 443–453.
Dixon, A. L., Liang, L., Moffatt, M. F., Chen, W., Heath, S., Wong, K. C. C., et al. (2007) A genome-wide association study of global gene expression. Nature Genetics, 39, 1202–1207.
Goring, H. H. H., Curran, J. E., Johnson, M. P., Dyer, T. D., Charlesworth, J., Cole, S. A., et al. (2007) Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nature Genetics, 39, 1208–1216.
Stranger, B. E., Nica, A. C., Forrest, M. S., Dimas, A., Bird, C. P., Beazley, C., et al. (2007) Population genetics of human gene expression. Nature Genetics, 39, 1217–1224.
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Rich, S.S. Approaching Biomarker Discovery through Genomics. J. of Cardiovasc. Trans. Res. 1, 21–24 (2008). https://doi.org/10.1007/s12265-007-9003-z
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DOI: https://doi.org/10.1007/s12265-007-9003-z