Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping in the eMERGE-PGx Study.

J Mol Diagn 2017 07 11;19(4):561-566. Epub 2017 May 11.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmoldx.2017.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500823PMC
July 2017
79 Reads

Publication Analysis

Top Keywords

clinical laboratories
12
concordance rate
8
clinical genotyping
8
genotype discrepancies
8
clinical
7
ngs
6
genotyping
5
1792 samples
4
retesting subset
4
primer hybridization
4
concordance
4
subset 1792
4
analytical quality
4
laboratory directors
4
directors determined
4
interfering primer
4
local laboratory
4
samples local
4
laboratories retesting
4
tested combinations
4

Similar Publications