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

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.

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.

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 (OR_females, 1.36; 95% CI, 1.29 to 1.44) than in men (OR_males, 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.

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.