Genomic Ancestry, CYP 2D6 , CYP 2C9 , and CYP 2C19 Among Latin Americans

We present the distribution of CYP 2D6 , CYP 2C9 , and CYP 2C19 variants and predicted phenotypes in 33 native and admixed populations from Ibero‐America ( n > 6,000) in the context of genetic ancestry ( n = 3,387). Continental ancestries are the major determinants of frequencies of the increased‐activity allele CYP 2C19*17 and CYP 2C19 gUM s (negatively associated with Native American ancestry), decreased‐activity alleles CYP 2D6*41 and CYP 2C9*2 (positively associated with European ancestry), and decreased‐activity alleles CYP 2D6*17 and CYP 2D6*29 (positively associated with African ancestry). For the rare alleles, CYP 2C9*2 and CYPC 19*17 , European admixture accounts for their presence in Native American populations, but rare alleles CYP 2D6*5 (null‐activity), CYP 2D6 ‐multiplication alleles (increased activity), and CYP 2C9*3 (decreased‐activity) were present in the pre‐Columbian Americas. The study of a broad spectrum of Native American populations from different ethno‐linguistic groups show how autochthonous diversity shaped the distribution of pharmaco‐alleles and give insights on the prevalence of clinically relevant phenotypes associated with drugs, such as paroxetine, tamoxifen, warfarin, and clopidogrel.