Variant in a Taste Receptor Locus Tied to Changes in the Use of Insomnia Medication

I have a new first-author paper out in Biological Psychiatry Global Open Science: Variant in a taste receptor locus tied to changes in the use of insomnia medication. This one took a long time to get right, and I find it particularly important — not just as a piece of genetics, but because the results point toward something a clinician could actually use today.

The problem with zopiclone

Zopiclone is one of the most commonly prescribed drugs for insomnia. It works, but it comes with a well-known and often-complained-about side effect: a persistent bitter or metallic taste, sometimes described as a taste of copper that lingers long after the pill is taken. For many patients this is tolerable. For others it is bad enough that they stop taking the drug or ask for something different.

What has never been clear is why some people are so much more sensitive to this than others. The taste experience is subjective, hard to measure systematically, and easy to dismiss as individual variation. But individual variation in biology usually has a genetic underpinning, and that is where this study starts.

A genome-wide look at medication switching

We used Icelandic prescription data from deCODE to identify people who had been prescribed zopiclone and then switched to a different sleep medication — zolpidem, which does not carry the same taste side effect profile. Switching is a noisy signal, but at the population scale of Icelandic data it becomes informative: if there is a genetic variant that reliably predicts who stops taking zopiclone and moves on to something else, that is telling you something real about drug tolerability.

We found exactly that. A variant near a taste receptor gene is significantly associated with switching away from zopiclone. The biological story is coherent: taste receptors vary across individuals, and those differences appear to translate into differences in how unpleasant the drug’s aftertaste actually is. People who carry the variant are more likely to find it intolerable enough to switch.

Why I find this particularly important

Most pharmacogenomics findings live in a gray area — they tell you about risk or metabolism, but the clinical implications are indirect and probabilistic. This result is different. If a patient carries a variant that predicts poor tolerability of zopiclone, you have an immediate, actionable alternative: prescribe zolpidem instead. No trial period of suffering through a side effect that was always going to be a problem. No months of follow-up before the switch happens on its own.

That matters especially for patients who are already dealing with something hard. Cancer patients, for example, are frequently prescribed medications with taste-based side effects — nausea, metallic tastes, and sensory distortions are common companions of chemotherapy and supportive care regimens. For someone already navigating a difficult treatment, getting a better-tolerated sleep medication is not a minor quality-of-life footnote. It is one fewer burden during a period when every such burden counts. The same logic applies here: if a genetic test could tell a prescribing physician upfront which patients will find zopiclone unpleasant, those patients could be steered toward zolpidem from the start.

We are not at routine pharmacogenomic prescribing yet — the infrastructure for that is still being built. But this kind of result is exactly the type that brings it closer.

A long time coming

This paper went through many iterations and a lot of careful work on the phenotype definition. Prescription switching is a messy endpoint: people switch medications for all kinds of reasons, and filtering the taste-related signal from the noise required thinking hard about the data. I am proud of how the analysis came together, and I think it is a good example of what large-scale population data — the kind that deCODE has been building for decades — makes possible. The variant would have been nearly invisible in a smaller cohort.

It is also a reminder that genetics does not always have to operate through some complicated pathway to be useful. Sometimes the mechanism is straightforward: a gene that shapes how something tastes, a drug with a distinctive taste, and a patient who has to decide whether to keep taking it.