Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping in the eMERGE-PGx Study
| Autor: | Laura J. Rasmussen-Torvik, Kimberly F. Doheny, Kejian Zhang, Stuart A. Scott, Ammar Husami, Michael D. Linderman, Sarah C. Stallings, Adam S. Gordon, Iftikhar J. Kullo, Robert R. Freimuth, Marylyn D. Ritchie, Wendy A. Wolf, Teri A. Manolio, Jared B. Hawkins, Lynn Ivacic, Berta Almoguera, Cynthia A. Prows, Renata Pellegrino, Hakon Hakonarson, Maureen E. Smith, Aniwaa Owusu Obeng |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genotype Genotyping Techniques Concordance Computational biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Humans Medicine Genotyping Alleles Genetics Polymorphism Genetic business.industry High-Throughput Nucleotide Sequencing Regular Article Sequence Analysis DNA Pharmacogenomic Testing 030104 developmental biology Pharmacogenetics 030220 oncology & carcinogenesis Research studies Molecular Medicine business |
| Zdroj: | The Journal of Molecular Diagnostics. 19:561-566 |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2017.04.002 |
| Popis: | There has been extensive debate about both the necessity of orthogonal confirmation of next-generation sequencing (NGS) results in Clinical Laboratory Improvement Amendments-approved laboratories and return of research NGS results to participants enrolled in research studies. In eMERGE-PGx, subjects underwent research NGS using PGRNseq and orthogonal targeted genotyping in clinical laboratories, which prompted a comparison of genotyping results between platforms. Concordance (percentage agreement) was reported for 4077 samples tested across nine combinations of research and clinical laboratories. Retesting was possible on a subset of 1792 samples, and local laboratory directors determined sources of genotype discrepancy. Research NGS and orthogonal clinical genotyping had an overall per sample concordance rate of 0.972 and per variant concordance rate of 0.997. Genotype discrepancies attributed to research NGS were because of sample switching (preanalytical errors), whereas the majority of genotype discrepancies (92.3%) attributed to clinical genotyping were because of allele dropout as a result of rare variants interfering with primer hybridization (analytical errors). These results highlight the analytical quality of clinically significant pharmacogenetic variants derived from NGS and reveal important areas for research and clinical laboratories to address with quality management programs. |
| Databáze: | OpenAIRE |
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