Assessment of a Pharmacogenomic Marker Panel in a Polypharmacy Population Identified from Electronic Medical Records

Abstract

Background: The ADME Core Panel assays 184 variants across 34 pharmacogenes, many of which are difficult to accurately genotype with standard multiplexing methods. Methods: We genotyped 326 frequently medicated individuals of European descent in Vanderbilt‘s biorepository linked to de-identified electronic medical records, BioVU, on the ADME Core Panel to assess quality and performance of the assay. We compared quality control metrics and determined the extent of direct and indirect marker overlap between the ADME Core Panel and the Illumina Omni1-Quad. Results: We found the quality of the ADME Core Panel data to be high, with exceptions in select copy number variants and markers in certain genes (notably CYP2D6). Most of the common variants on the ADME panel are genotyped by the Omni1, but absent rare variants and copy number variants could not be accurately tagged by single markers. Conclusion: Our frequently medicated study population did not convincingly differ in allele frequency from reference populations, suggesting that heterogeneous clinical samples (with respect to medications) have similar allele frequency distributions in pharmacogenetics genes compared with reference populations.

Original submitted 25 October 2012; Revision submitted 20 March 2013

KEYWORDS::

• ADME
• biorepository
• BioVU
• CYP2D6
• genotyping
• Illumina
• medicine rare variants
• personalized medicine
• precision

Acknowledgements

The authors would like to thank AR Baker and VM Youngblood for their assistance in organizing a portion of this data set. The Vanderbilt University Center for Human Genetics Research, Computational Genomics Core provided computational and/or analytical support for this work.

Financial & competing interests disclosure

The data set(s) used for the analyses described were obtained from Vanderbilt University Medical Center‘s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. This study was supported in part by RC2 GM092618. 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 of research

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 data set(s) used for the analyses described were obtained from Vanderbilt University Medical Center‘s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. This study was supported in part by RC2 GM092618. 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.