Pharmacogenomic survey of Qatari populations using whole-genome and exome sequences.

The Arabs represent one of the most genetically heterogeneous populations characterized by a high prevalence of Mendelian disorders due to consanguinity. Population-scale genomic datasets provide a unique opportunity to understand the epidemiology of variants associated with differential therapeutic response. We analyzed publicly available genomic data for 1005 Qatari individuals encompassing five subpopulations. The frequencies of known and novel pharmacogenetic variants were compared with global populations. Impact of genetic substructure on the pharmacogenetic landscape of the population was studied. We report an average of three clinically actionable pharmacogenetic variants with FDA-recommended genetic testing per Qatari individual regardless of their genetic ancestry. We observed extensive differences in the frequencies of clinically actionable pharmacogenetic variants among the Qatari subpopulations. Our analysis revealed 3579 deleterious pharmacogenetic variants potentially altering the function of 1163 genes associated with 1565 drugs. This study has thus compiled the first comprehensive landscape of pharmacogenetic variants for any Arab population.