Performance of Exome Sequencing for Pharmacogenomics

Abstract

Aim: We present the potential false-negative rate of exome sequencing for the detection of pharmacogenomic variants. Materials & Methods: Depth of coverage of 1928 pharmacogenomically relevant variant positions was ascertained from 62 exome-sequenced samples. Results: Approximately 14% of the 1928 variant locations examined had inadequate depth of coverage (<20×). The variants with inadequate coverage were predominantly located outside of protein-coding portions and included some clinically relevant variant positions, such as the warfarin VKORC1 variant. Conclusion: While the use of exome sequencing is becoming more prevalent in fundamental research, clinical trials and clinical use; there is a possibility of false-negative results. The possible quality issues such as false-negative rate should be considered with the use of exome sequencing.

Keywords::

• exome sequencing
• pharmacogenomics
• warfarin

Financial & competing interests disclosure

The work was supported in part by the NIH-NCI Cancer Center Core grant (P30CA56036 to PF) and by TJU Institutional funds (ER). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The work was supported in part by the NIH-NCI Cancer Center Core grant (P30CA56036 to PF) and by TJU Institutional funds (ER). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.