Evaluating genotype–treatment interactions for high-risk medications in British general practice: a retrospective cohort study using UK Biobank

Kinan Mokbel; Michael Weedon; Rob Daniels; Victoria Moye; Leigh Jackson

doi:10.3399/BJGP.2024.0806

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Genotype testing
Kinan Mokbel

Published on: 09 February 2026
Genotype testing
John Sharvill

Published on: 02 February 2026

Published on: (9 February 2026)
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Genotype testing
Kinan Mokbel, Senior Lecturer, University of Exeter
Thank you for reading the paper and for the helpful question. The examples you cite (azathioprine, carbamazepine, clopidogrel) are indeed the well-established “test-before-prescribing” scenarios many of us associate with pharmacogenetics.

The key point for interpreting our findings is scope; Our aim was not to evaluate every genotype-guided prescribing recommendation across all medicines used by UK Biobank participants. Rather, we used a pre-specified, pharmacovigilance-led approach to focus on a defined set of medicines and outcomes that met our inclusion criteria within the UK Biobank exposure and outcome framework, and then tested genotype-treatment interactions for the eligible variant-drug pairs in that set. As a result, several classic gene-drug pairs, including those you mention, were not part of the interaction analyses we reported.

Their absence should therefore not be read as evidence that these interactions are unimportant or absent in practice, nor that they “did not show up” despite a cohort of 500,000 participants. They were simply outside the scope of this particular study, which reports results for a deliberately defined subset of medication classes and outcomes aligned to our selection strategy.

Competing Interests: None declared.
Published on: (2 February 2026)
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John Sharvill, GP, Nil
I am more muddled now about genotype testing after reading this article than before. For some time, genotype testing pre-using azathioprine was standard. More recently, NICE advised this before using carbamazepine, and several sources have at least since December for those being prescribed clopidogrel. Did none of these interactions show up in the 500,000 people in the study?

Competing Interests: None declared.

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