Citations 2
Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects
Volpi, Simona , Bult, Carol J. , Chisholm, Rex L. , Deverka, Patricia A. , Jacob, Howard J., Kasapi, Melpomeni , McLeod, Howard L. , Roden, Dan M. , Green, Eric D. , Rodriguez, Laura Lyman , Aronson, Samuel , Cavallari, Larisa H. , Denny, Joshua C. , Dressler, Lynn G., Johnson, Julie A. , Leeder, J. Steven , Piquette‐Miller, Micheline , Rasmussen‐Torvik, Laura J. , Ritchie, Marylyn D. , Skaar, Todd C. , Wagle, Nikhil , Weinshilboum, Richard M. , Weitzel, Kristin, Wildin, Robert S. , Manolio, Teri A. , Relling, Mary V. , Weinshilboum, Richard, Denny, Joshua C , Ginsburg, Geoffrey S. , Roden, Dan M. , Williams, Marc S , Klein, Teri E. , Perera, Minoli A. , Rehm, Heidi L. , Weinshilboum, Richard M. , Wilson, John T. , Cavallari, Larisa H , Rasmussen-Torvik, Laura J
Clinical Pharmacology & Therapeutics | February 21, 2018 | Volume: 103 | Issue: 5 | Pages: 778-786
Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them.
Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network
Crosslin, DR, Owusu‐Obeng, Aniwaa, Wallace, John R. , Almoguera, Berta , Basford, MA, Bielinski, Suzette J. , Carrell, DS, Connolly, John J. , Doheny, KF, Gallego, CJ, Gordon, Allan , Kirby, Jacqueline, Kitchner, Terrie, Manzi, Shannon , Mejia, A R, Pan, Vivian , Perry, Cassandra, Peterson, JF, Prows, CA, Ralston, James D. , Scott, Stuart A. , Scrol, Aaron, Smith, Maureen E. , Stallings, SC, Veldhuizen, Tamra L., Wolf, W.A., Volpi, Simona , Wiley, Kenneth L , Manolio, Teri A. , Böttinger, Erwin P. , Brilliant, MH, Carey, David J. , Chisholm, Rex L. , Chute, CG, Jl, Haines, Håkonarson, Håkon , Harley, JB, Holm, Ingrid A. , Kullo, IJ, Jarvik, GP, Larson, EB, McCarty, Catherine A. , Williams, MS, Denny, Joshua C. , Rasmussen‐Torvik, LJ, Roden, DM, Ritchie, MD, Rasmussen‐Torvik, Laura J. , Jarvik, Gail P. , Peterson, Josh F. , Bush, William S. , Wallace, J, Crawford, Dana C. , Keating, Brendan J. , Perry, CL, Peterson, JF, Stallings, SC, Li, R, Roden, DM, Ritchie, M.D., Holm, Ingrid A , Hakonarson, Hakon , Denny, Joshua C , Jarvik, Gail P , Bielinski, Suzette , Gordon, Adam S , Connolly, John J , Peterson, Josh F , Scott, Stuart A , Rasmussen-Torvik, Laura J
Clinical Pharmacology & Therapeutics | February 9, 2016 | Volume: 100 | Issue: 2 | Pages: 160-169
Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.