title: Assessing gene-gene interactions in pharmacogenomics.
abstract: In pharmacogenomics studies, gene-gene interactions play an important role in characterizing a trait that involves complex pharmacokinetic and pharmacodynamic mechanisms, particularly when each involved feature only demonstrates a minor effect. In addition to the candidate gene approach, genome-wide association studies (GWAS) are widely utilized to identify common variants that are associated with treatment response. In the wake of recent advances in scientific research, a paradigm shift from GWAS to whole-genome sequencing is expected, because of the reduced cost and the increased throughput of next-generation sequencing technologies. This review first outlines several promising methods for addressing gene-gene interactions in pharmacogenomics studies. We then summarize some candidate gene studies for various treatments with consideration of gene-gene interactions. Furthermore, we give a brief overview for the pharmacogenomics studies with the GWAS approach and describe the limitations of these GWAS in terms of gene-gene interactions. Future research in translational medicine promises to lead to mechanistic findings related to drug responsiveness in light of complex gene-gene interactions and will probably make major contributions to individualized medicine and therapeutic decision-making.
authors.affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Guochuan E
authors.initials: GE
authors.lastname: Tsai
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
mesh_terms: D004843:Epistasis, Genetic; D015870:Gene Expression / Q000187:drug effects; D055106:Genome-Wide Association Study; D006801:Humans; D016571:Neural Networks, Computer; D004364:Pharmaceutical Preparations; D010597:Pharmacogenetics
chemical_list: D004364:Pharmaceutical Preparations