Clinically Relevant Pharmacogenomic Variant Frequencies in Kazakh, Russian, and Uzbek Population Groups Residing in Kazakhstan

Abstract

Simple Summary Central Asian populations remain poorly represented in pharmacogenomic research, limiting the availability of population-specific information for precision medicine. In this study, we analyzed 112 directly genotyped, clinically relevant pharmacogenomic variants in 1301 Kazakh, Russian, and Uzbek individuals residing in Kazakhstan. The frequencies of these variants were compared among the three population groups and with the contemporary gnomAD v4.1 genome and exome reference datasets. Of the 112 variants, matching reference allele-frequency data for the predefined reported allele were available in at least one of the two gnomAD datasets for 103 variants; no corresponding gnomAD frequency was available for the remaining 9 variants. Several variants showed notable population-specific patterns, including variants in NUDT15, SLCO1B1, VKORC1, and UGT1A1, which are relevant to thiopurine toxicity, statin-associated adverse effects, warfarin dose variability, and irinotecan-related toxicity. The comparisons showed that the observed frequency patterns could not be consistently represented by a single broad global reference group. These findings provide an updated pharmacogenomic frequency resource for Kazakhstan and highlight the need for larger, more balanced, and clinically integrated studies in Central Asia.