2015-LB: Actionable Pharmacogenomic Variants in the Kuwaiti Population

Pharmacogenomics plays a pivotal role in advancing precision medicine by addressing critical public health concerns like Adverse Drug Reactions (ADRs) and dosage regulations. The emergence of Next Generation Sequencing (NGS) techniques, coupled with the rapid expansion of pharmacogenomic data, offers a unique opportunity to accelerate progress in this field. This study aims to investigate the frequency and classification of actionable pharmacogenomic findings in the Kuwaiti population. Exome sequence data from 474 individuals of Kuwaiti descent were analyzed to evaluate the quantity and clinical relevance of incidental pharmacogenomic variants. Using a panel of 293 pharmacogenomic genes, the dataset was filtered, and resulting variants were categorized based on variant type, population frequency, functional impact, pathogenicity, and annotations from PharmGKB and ClinVar databases. In Clinvar, 33 missense variants related to drug response were identified. Additionally, 591 rare pharmacogenomic variants were detected in this population, predicted to be pathogenic using pathogenicity prediction tools. We observed 15 known pharmacogenomic variants classified as actionable (PharmGKB 1A or 1B level of evidence), impacting approximately 16 drugs. In conclusion, this study provides a comprehensive examination of known pharmacogenomic variants in the Kuwaiti population, highlighting their potential impact on drug response. We observed a higher frequency of genetic variants affecting drug response to medications like Ivacaftor, Tramadol, Efavirenz, and Capecitabine compared to global populations. Notably, a prominent actionable variant identified in this population is a VKORC1 variant associated with warfarin dosage. These findings underscore the significance of pharmacogenomic considerations in optimizing drug therapy for Kuwaiti individuals.