Reconstructing the pharmacogenomic landscape of psychiatric medication metabolism in the Indian population

With the advent of genomic technologies, pharmacogenomics has evolved significantly. Such advancement facilitates comprehensive identification of common and rare alleles crucial for psychiatry treatments, especially in context of Indian psychiatric patients who are genetically diverse and for whom data is limited. This study explores the pharmacogenomic spectrum of CYP2C19, CYP2D6, and CYP2C9 genes in an Indian psychiatric cohort of 383 individuals (264 patients, 119 controls) using Axiom PMD Array. Beyond common phenotypes like CYP2C19 *1/*2, we identified rare functional phenotypes including CYP2C19 *1/*34, CYP2C9 *1/*11 and CYP2D6 *4/*5 that are frequently overlooked in regular screenings. Interestingly, 3% of individuals were identified as most likely non-responders to medications metabolized by these three enzymes, suggesting the importance of platforms that cover both common and rare alleles in populations with high diversity. The study observed 13.26% poor CYP2C19 metabolizers, 2.27% poor CYP2D6 metabolizers, and 3.41% poor CYP2C9 metabolizers in the psychiatric cohort. The study identifies three percent of the cohort shows compromised metabolism across all three genes, emphasizing that comprehensive screening of common along with rare functional variants is essential for personalized psychiatric treatment in India. Garg et al. explore the pharmacogenomic spectrum of CYP2C19, CYP2D6, and CYP2C9 genes in an Indian psychiatric cohort. They identify a subgroup with compromised metabolism across all three genes suggesting rare function variant screening may be warranted. Psychiatric medications work differently across various ethnic groups due to differences in gene pool. India has many genetically diverse ethnicities, but we lack data on the genes that affect how psychiatric drugs work in Indian populations. This study examined three important genes (CYP2C19, CYP2D6 and CYP2C9) that regulates how the body processes psychiatric medications. In this study we examined 264 psychiatric patients and 119 healthy individuals using an advanced genetic testing platform that can detect both common and rare genetic variations.We observed that 3% of individuals were identified as most likely non-responders to medications processed by these three studied genes, suggesting standard treatments may not work well for them. Our findings show that testing for only the most frequently reported genetic variants may miss important information in genetically diverse Indian populations. This study suggests that comprehensive genetic testing examining a wide range of genetic variations rather than just common ones can help clinicians to select the most appropriate medications and doses for each patient, ultimately improving treatment outcomes.