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Assessing Gene-Gene Interactions in Pharmacogenomics

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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.

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Acknowledgments

The authors extend their sincere thanks to Vita Genomics, Inc., the National Science Council, Taiwan (NSC-97-2314-B-039-006-MY3 and NSC-100-2627-B-039-001), the National Health Research Institutes, Taiwan (NHRI-EX-101-9904NI), the Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH101-TD-B-111-004), and China Medical University Hospital, Taiwan (DMR-98-092 and DMR-99-115) for funding this research.

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Authors and Affiliations

  1. Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan

    Hsien-Yuan Lane

  2. Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

    Hsien-Yuan Lane &  Eugene Lin

  3. Sunshine Psychiatric Hospital, Taichung, Taiwan

    Hsien-Yuan Lane

  4. Los Angeles Biomedical Research Institute and Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, CA, USA

    Guochuan E. Tsai

  5. Vita Genomics, Inc., 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan

    Eugene Lin

Authors
  1. Hsien-Yuan Lane
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  2. Guochuan E. Tsai
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  3. Eugene Lin
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Corresponding author

Correspondence to Eugene Lin.

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Lane, HY., Tsai, G.E. & Lin, E. Assessing Gene-Gene Interactions in Pharmacogenomics. Mol Diagn Ther 16, 15–27 (2012). https://doi.org/10.1007/BF03256426

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  • DOI: https://doi.org/10.1007/BF03256426

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