Nanopore sequencing-based genotyping suggested an association between CYP2D6 function and susceptibility to anxiety and depression.

Objective: CYP2D6 activity has been inconsistently associated with anxious and depressive personality traits. The inconsistency may stem from limitations of targeted genotyping, employed in most previous studies, leading to undetected errors in metabolic classification. Using a nanopore sequencing-based method, we comprehensively genotyped CYP2D6 alleles in a small cohort of 96 Malaysians and re-examined the relationship between CYP2D6 activity and susceptibility to anxiety and depression.
Results: In keeping with prior studies, CYP2D6*10 was found to be the most common defective allele. Nearly half of the (48.5%) participants were classified as intermediate and poor metabolizers. Linear regression analysis suggested that impaired CYP2D6 activity could be a predictor of anxiety and depression, consistent with the putative role of CYP2D6 in the synthesis of serotonin and dopamine, the mood-boosting neurotransmitters. We hope this brief report will prompt larger-scale studies to further elucidate the contribution of CYP2D6 to the genetic underpinnings of mental well-being.
Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved (UKM PPI.800-1/1/5/JEP-2019-391) by the Research Ethics Committee UKM (Human). Informed consent was obtained from all participants. The study was performed in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2025. The Author(s).)