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McNamee. J Transl Genet Genom 2018;2:20. I https://doi.org/10.20517/jtgg.2018.24 Page 3 of 7

look for novel ways to offer their patients treatment. There are around 70,000 rare diseases, so as a category
rare diseases are not actually so rare and affect 6%-7% of the UK population. This prominence of rare diseases,
[10]
and their link to genetic variants, led to the initiation of the UK 100,000 genome project . Genomics England
was set up to sequence the whole genomes of 100,000 patients suffering with rare diseases and cancers (along
with close family members) to provide a diagnosis for their condition and to potentially offer them some
treatment. Genomic Medicine Centers set up across England sequenced participant’s samples and collated the
data into a central repository to create a rich resource for scientists to investigate the genetic basis to disease
and research drug-gene interactions. The legacy of this project is the launch in spring 2019 of a UK wide NHS
[11]
genomic medicine service (GMS) that links the established Genomic Medicine Centers with other clinical
departments, such as clinical pharmacologists, geneticists, etc. A panel of experts will review the scientific
evidence for drug-gene interactions and develop a central directory for the GMS that lists all the variants
proven to relate to drug efficacy (the directory constantly updated as knowledge of drug-gene interactions
increases). The GMS will offer a range of sequencing and panel tests to general practioners (and other hospital
clinicians) to diagnose disease genotype, and use algorithms to interrogate the test data to identify any genetic
variants listed in the directory known to be associated with drug-gene interactions. Computerised drug deci-
sion software will interrogate patient results and alert clinicians when variants that pose a prescribing risk are
detected, allowing patients to be prescribed either a lower dose or alternative drug treatment.

The Ubiquitous Pharmacogenetics (UPGx) consortium pre-emptive pharmacogenomics testing for prevent-
[12]
ing adverse drug reactions study is another project evaluating the effectiveness of implementing testing
into various healthcare systems across Europe. In a similar way to the GMS, UPGx is investigating if apply-
ing a selected group of pharmacogenomics markers into the diagnostic process improves prescribing and
saves on healthcare costs. Pharmacogenomics data on drug-gene interactions linked into electronic clinical
decision support systems will alert prescribers/pharmacists when a patient’s electronic health record contain
a pharmacogenomics variant that puts the patient at risk of an adverse drug reaction to the drug they are
prescribing.

The practice of personalized genomic medicine is worldwide and these are just a couple of examples of proj-
ects that are leading the introduction into the clinic. The percentage of precision medicine drugs approved
[13]
by the FDA annually has already increased from 5% in 2015 to 35% in 2017 . Almost 50% of the drugs ap-
proved were for treatment for conditions other than oncology demonstrates how widespread the use person-
alized genomic medicine is becoming across all sectors of medicine.

Drug safety
Most drugs are only effective on average for between 50%-75% of the general population and there are exam-
[14]
ples of oncology blockbuster drugs where efficacy is as low as 25% . Whilst many patients may simply have
no response to a drug, genetic variants in metabolic pathways are responsible for causing adverse drug reac-
tions which can be life threatening for some patients. For example, the effect of such a variant caused cata-
[15]
strophic hypersensitivity to the drug abacavir in some HIV patients . Pre-emptive genotyping of patients
prior to prescribing abacavir has significantly reduced the number of patients suffering this life threatening
adverse drug reaction.

In the UK alone approximately 8000 hospital beds are occupied at any one time with patients suffering from
[15]
adverse drug reactions, placing a huge £2 billion burden on the healthcare system . Furthermore, there is
a significant cost to the pharmaceutical industry when a drug has to be withdrawn post marketing due to
safety concerns. Incorporating pharmacogenetics data into the prescribing and drug development processes
[16]
is crucial to support delivering patients safer and more effective treatments . Currently there are only a few
genetic variants linked to drug-gene interactions compared to the number of drugs on the market, but as
more pharmacogenetics data becomes available this number will steadily increase.