Recent advances in genomic technologies have enabled the identification of thousands of genetic variations that are associated
with hundreds of complex human diseases or traits in genome-wide association studies (GWAS). The large number of genetic loci uncovered
for each disease or trait along with the difficulty in pinpointing the underlying genes and mechanisms further testify to the complexity
of human pathophysiology. To alleviate the challenges of GWAS, systems biology approaches have been utilized to map the molecular
mechanisms underlying complex human diseases/traits via the integration of genetic variation, functional genomics (such as genetics
of gene expression), pathways, and molecular networks. Similar approaches have been applied to a spectrum of drug metabolizing
enzymes to discover novel functional genetic variations that affect the expression or activities of these enzymes as well as to define the
regulatory pathways/networks of genes involved in drug metabolism and toxicology in key human tissues. We envision that the increased
coverage of functional genetic polymorphisms, the availability of drug metabolism-centered gene networks, and the maturing methodologies
previously developed for understanding complex human diseases can be applied to pharmacogenomic and toxicogenomic studies
to further our understanding of inter-individual variability in drug efficacy and toxicity and eventually help direct personalized medicine.
Keywords: Drug response, functional genomics, genome-wide association study, molecular network, pharmacogenomics, single nucleotide
polymorphism, systems biology, toxicogenomics, Genomics, genome-wide association studies, pathophysiology, efficacy, Traits, Key human tissues, Genetic loci.
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Published on: 29 July, 2012
Page: [952 - 967]