Population Genetics of Pharmacogenetic Variants in a Greek Psychiatric Cohort of over 3000 Individuals

Psychiatric disorders affect nearly one billion people worldwide and remain a major therapeutic challenge due to frequent treatment resistance. Pharmacogenetics provides a precision-informed approach by accounting for interindividual variability in drug metabolism and response, and population-specific data offer valuable information for therapeutic considerations. This study analyzed 3011 Greek individuals to assess 24 pharmacogenetic variants across 13 genes. Genotyping was performed using TaqMan OpenArray^® assays, and metabolic phenotypes were predicted based on established genotype-to-phenotype translation guidelines. Allele frequencies were compared with those in European, African, and East Asian populations. Population structure and genetic differentiation were evaluated using Principal Component Analysis (PCA), K-means clustering, fixation index (F_ST), and STRUCTURE analysis. Results indicated that most allele frequencies in Greeks aligned with those in European populations, while several <i>CYP2D6</i> and <i>CYP2C19</i> variants differed significantly from those in African and East Asian cohorts. PCA and clustering confirmed strong European affinity, supported by low F_ST values, whereas STRUCTURE revealed minimal non-European admixture. Predicted metabolic phenotypes showed that 36%, 57.7%, and 41.6% of individuals exhibited altered CYP2D6, CYP2C19, and CYP2C9 activity, respectively. These findings highlight clinically actionable variation in the Greek population and emphasize the use of population-specific pharmacogenetic data to inform optimized strategies in precision psychiatry.