| Title: | Variant in a Taste Receptor Locus Tied to Changes in the Use of Insomnia Medication |
| Journal: | Biological Psychiatry Global Open Science |
| Published: | 10 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41492454/ |
| DOI: | https://doi.org/10.1016/j.bpsgos.2025.100652 |
Publication 18975
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Abstract
Background: Zopiclone and zolpidem are widely prescribed hypnotic medications for insomnia, sharing similar efficacy but differing in side-effect profiles, particularly concerning taste disturbances. Identifying genetic predictors of intolerance to these medications could inform personalized treatment strategies.</p>
Methods: We conducted a genome-wide association study to identify genetic variants associated with switching between zopiclone and zolpidem in 57,669 Icelanders, using electronic prescription data from Iceland (2003-2020), and 6590 British individuals from the UK Biobank (1990-2017). We included individuals who had received at least 3 prescriptions of either drug. We also investigated data on bitter taste perception using quinine taste test data from 2238 Icelandic individuals.</p>
Results: A common sequence variant, rs6488335-G, within the TAS2R ∗ bitter taste receptor gene locus on chromosome 12, was associated with an increased likelihood of switching from zopiclone to zolpidem (Iceland: odds ratio [OR], 1.29; 95% CI, 1.24 to 1.35; United Kingdom: OR, 1.34; 95% CI, 1.12 to 1.59) and a decreased likelihood of switching in the reverse direction. The effect was more pronounced in women (ORfemales, 1.36; 95% CI, 1.29 to 1.44) than in men (ORmales, 1.19; 95% CI, 1.11 to 1.27). While the variant is associated with bitter taste perception of quinine, conditional analyses suggest that the pharmacogenetic association with drug switching is independent of taste perception.</p>
Conclusions: Our findings indicate that carriers of the rs6488335-G variant, particularly homozygous women, were more likely to switch from zopiclone to zolpidem, potentially due to heightened sensitivity to taste-related side effects. Preemptive genetic testing could guide clinicians in prescribing zolpidem over zopiclone for individuals at risk, thereby reducing health care visits and improving treatment adherence.</p>
24 Authors
- Gudmundur Einarsson
- Hannes K. Arnason
- Rosa S. Gisladottir
- Gyda Bjornsdottir
- Thorgeir E. Thorgeirsson
- Astros Skuladottir
- G. Bragi Walters
- Saedis Saevarsdottir
- Magnus K. Magnusson
- Gisli H. Halldorsson
- Audunn S. Snaebjarnarson
- Hafsteinn Einarsson
- Gardar Sveinbjornsson
- Hannes Helgason
- Vinicius Tragante
- Gudrun A. Jonsdottir
- Hildur M. Aegisdottir
- Ingileif Jonsdottir
- Thorarinn Gislason
- Gudmar Thorleifsson
- Patrick Sulem
- Hreinn Stefansson
- Daniel F. Gudbjartsson
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 42256 | Neurogenetics - the role of genetics in normal and abnormal functioning of the Central Nervous System (CNS) |
Enabling scientific discoveries that improve human health