From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions.

@article{citeulike:2866445, abstract = {A brief history of human genetics and genomics is provided, comparing recent progress in those fields with that in pharmacogenetics and pharmacogenomics, which are subsets of genetics and genomics, respectively. Sequencing of the entire human genome, the mapping of common haplotypes of single-nucleotide polymorphisms (SNPs), and cost-effective genotyping technologies leading to genome-wide association (GWA) studies - have combined convincingly in the past several years to demonstrate the requirements needed to separate true associations from the plethora of false positives. While research in human genetics has moved from monogenic to oligogenic to complex diseases, its pharmacogenetics branch has followed, usually a few years behind. The continuous discoveries, even today, of new surprises about our genome cause us to question reviews declaring that "personalized medicine is almost here" or that "individualized drug therapy will soon be a reality." As summarized herein, numerous reasons exist to show that an "unequivocal genotype" or even an "unequivocal phenotype" is virtually impossible to achieve in current limited-size studies of human populations. This problem (of insufficiently stringent criteria) leads to a decrease in statistical power and, consequently, equivocal interpretation of most genotype-phenotype association studies. It remains unclear whether personalized medicine or individualized drug therapy will ever be achievable by means of DNA testing alone.}, address = {Division of Human Genetics, Department of Pediatrics \& Molecular Developmental Biology, Cincinnati, Ohio 45267-0056, USA. dan.nebert@uc.edu}, author = {Nebert, D. W. and Zhang, G. and Vesell, E. S. }, citeulike-article-id = {2866445}, doi = {10.1080/03602530801952864}, issn = {1097-9883}, journal = {Drug metabolism reviews}, keywords = {personalized-medicine, pharmacogenetics, pharmacogenomics}, number = {2}, pages = {187--224}, posted-at = {2008-06-05 17:51:55}, priority = {2}, title = {From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions.}, url = {http://dx.doi.org/10.1080/03602530801952864}, volume = {40}, year = {2008} }

TY - JOUR ID - citeulike:2866445 L3 - citeulike-article-id:2866445 TI - From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. JF - Drug metabolism reviews VL - 40 IS - 2 SP - 187 EP - 224 AD - Division of Human Genetics, Department of Pediatrics & Molecular Developmental Biology, Cincinnati, Ohio 45267-0056, USA. dan.nebert@uc.edu SN - 1097-9883 N2 - A brief history of human genetics and genomics is provided, comparing recent progress in those fields with that in pharmacogenetics and pharmacogenomics, which are subsets of genetics and genomics, respectively. Sequencing of the entire human genome, the mapping of common haplotypes of single-nucleotide polymorphisms (SNPs), and cost-effective genotyping technologies leading to genome-wide association (GWA) studies - have combined convincingly in the past several years to demonstrate the requirements needed to separate true associations from the plethora of false positives. While research in human genetics has moved from monogenic to oligogenic to complex diseases, its pharmacogenetics branch has followed, usually a few years behind. The continuous discoveries, even today, of new surprises about our genome cause us to question reviews declaring that "personalized medicine is almost here" or that "individualized drug therapy will soon be a reality." As summarized herein, numerous reasons exist to show that an "unequivocal genotype" or even an "unequivocal phenotype" is virtually impossible to achieve in current limited-size studies of human populations. This problem (of insufficiently stringent criteria) leads to a decrease in statistical power and, consequently, equivocal interpretation of most genotype-phenotype association studies. It remains unclear whether personalized medicine or individualized drug therapy will ever be achievable by means of DNA testing alone. KW - personalized-medicine KW - pharmacogenetics KW - pharmacogenomics AU - Nebert, DW AU - Zhang, G AU - Vesell, ES PY - 2008/// UR - http://dx.doi.org/10.1080/03602530801952864 ER -