Requirements for comprehensive pharmacogenetic genotyping platforms.

Abstract:

:Recent research highlighted the large extent of rare variants in pharmacogenes and, on this basis, it was estimated that rare variants account for 30-40% of the functional variability in pharmacogenes. It has been proposed that comprehensive next-generation sequencing (NGS)-based sequencing of pharmacogenes could soon be a cost-effective methodology for clinical routine genotyping. Yet, multiple challenges on technical, interpretative and ethical levels need to be overcome to enable the reasonable dissemination of comprehensive pharmacogenetic genotyping, that includes rare genetic variation, into clinical practice. We argue that current pre-emptive pharmacogenetic testing cannot be based on comprehensive approaches but needs to be restricted to validated variants. Rather, comprehensive strategies should only be used for retrospective analyses of patients exhibiting unanticipated drug responses. Thereby, subsequent to computational analyses and functional validations, emerging variants with confirmed functional relevance can be incorporated into candidate genotyping strategies, thus refining and enhancing future pre-emptive genetic testing.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Lauschke VM,Ingelman-Sundberg M

doi

10.2217/pgs-2016-0023

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

917-24

issue

8

eissn

1462-2416

issn

1744-8042

journal_volume

17

pub_type

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