Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans.

We present the distribution of CYP2D6, CYP2C9, and CYP2C19 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 CYP2C1917 and CYP2C19 gUMs (negatively associated with Native American ancestry), decreased-activity alleles CYP2D641 and CYP2C92 (positively associated with European ancestry), and decreased-activity alleles CYP2D617 and CYP2D629 (positively associated with African ancestry). For the rare alleles, CYP2C92 and CYPC1917, European admixture accounts for their presence in Native American populations, but rare alleles CYP2D65 (null-activity), CYP2D6-multiplication alleles (increased activity), and CYP2C9*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.