The gene is highly polymorphic, causing large interindividual variability in the metabolism of several clinically important drugs. The authors investigated the diversity and distribution of alleles in Indians using whole genome sequences (N = 1518). Functional consequences were assessed using pathogenicity scores and molecular dynamics simulations. The analysis revealed population-specific alleles (, , , , , ) and remarkable differences in variant and phenotype frequencies with global populations. The authors observed that one in three Indians could benefit from a dose alteration for psychiatric drugs with accurate phenotyping. Molecular dynamics simulations revealed large conformational fluctuations, confirming the predicted reduced function of and alleles. The findings emphasize the utility of comprehensive profiling for aiding precision public health.
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