Pharmacogenomics: a worthwhile genetic test for the over 60s?
From sequencing your entire genome enabling medical diagnoses and treatment plans, to testing for individual high-risk disease genes, the genetic testing market is growing faster than ever. Unlike many other diagnostic procedures, genetic tests remain stable over time and in theory only need to be done once. But despite being able to sequence an entire genome cheaply and quickly these days, for most people it remains difficult to know how to interpret the findings in a meaningful way. This is particularly true as you age since many diseases with a largely hereditary component present earlier in life or are useful to consider when family planning, therefore it can feel less effective to test your genome the older you get.
Pharmacogenetic testing is perhaps an exception to this. Pharmacogenomics show how your individual genes affect your response to medicines. This science matters more than ever after the age of 60 when multiple prescriptions are increasingly common and therefore stakes of adverse effects and ineffective drugs are higher.
Most people carry pharmacogenomic variations
From large population studies we know that nearly everyone (>95% of people) has at least one genetic variant that affects how they metabolise or respond to commonly prescribed medicines. Genes encoding the enzymes that metabolise drugs vary significantly between individuals and this means that the same medication can differ in effectiveness or have risk of side effects for different people.
This matters more for some drugs than others. For example, almost 30% of people of European ancestry carry CYP2C19 variants that reduce activation of clopidogrel, with much higher proportions in Asian populations. SLCO1B1 variants substantially increase simvastatin-related myopathy risk and CYP2D6 variants alter response to codeine.
Drug effectiveness is less universal than we assume
In some treatment areas it is very common for patients not to achieve a meaningful clinical response with a given first-line medication. Although kidney function, liver function, drug interactions, frailty and adherence all play a part, genotype plays a big role for some medications. For example, response rates to antidepressants, statins, antiplatelets, and proton-pump inhibitors can vary greatly by genotype due to genetic variation in drug targets and metabolic pathways. So although understanding your individual genotype can’t completely predict how you will react to different medications, it can remove a lot of guesswork.
Adverse drug reactions are common and costly
An estimated 6.5% of hospital admissions stem from adverse drug reactions (ADRs). Older adults are particularly at risk as they are often taking multiple medications, and ADRs in this group account for up to 30% of admissions. ADRs contribute to morbidity, loss of independence, and healthcare costs and many of them are predictable based on pharmacokinetics and pharmacodynamics thus understanding pharmacogenomic variation between individuals can help avoid ADRs.
Evidence for pharmacogenetics is growing
A recent study using a 12-gene pharmacogenetic panel demonstrated an almost 30% reduction in ADRs compared with usual care, and was shown to be overall cost-effective, underscoring the potential of pharmacogenomics to reduce avoidable harm and optimise therapy. This evidence aligns with prior smaller observational studies showing genotype-guided prescribing can reduce drug toxicity (e.g. reduce bleeding with genotype-guided antiplatelet selection) and improve therapeutic outcomes.
What does this all mean?
At present, there is not strong enough cost-effectiveness evidence for pre-emptive pharmacogenetic testing to be offered routinely across the NHS. NICE has approved testing in specific, high-risk settings (for example if you are about to start an uncommon high-risk medication) but broad panel testing for the general population has not yet met the economic threshold for universal rollout. The NHS Genomic Medicine Service oversees this, and there is active evaluation of how pharmacogenomics could be incorporated more systematically, but we are not there yet.
Private testing is available but the question is whether testing will meaningfully change your care. Almost everyone carries pharmacogenomic variants that influence drug response; recognising this helps explain why “standard” doses work for some people and not others, or why some people get side effects from medicines that others don’t. This isn’t an issue when you’re not taking medication often but if you are taking or likely to start medications such as clopidogrel, certain statins, PPIs, opioids, antidepressants or immunosuppressants, testing is likely to yield actionable information that can help influence your response to medications and risk of side effects.
Among the various forms of consumer genetic testing, pharmacogenomics is one of the few areas where the biological mechanisms are well characterised, prescribing guidelines exist, and clinical decisions can change as a result. Therefore as you get older, it is worth considering having this knowledge so you can make more informed decisions about which medications to take and which to avoid.
