Local ancestry informed GWAS of warfarin dose requirement in African Americans identifies a novel CYP2C19 splice QTL.

ABSTRACT: African Americans (AAs) are underrepresented in pharmacogenomics which has led to a significant gap in knowledge. AAs are admixed and can inherit specific loci from either their African or European ancestor, known as local ancestry (LA). A previous study in AAs identified single nucleotide polymorphisms (SNPs) located in the CYP2C cluster that are associated with warfarin dose. However, LA was not considered in this study. An IWPC cohort (N=340) was used to determine the LA-adjusted association with warfarin dose. Ancestry-specific GWAS's were conducted with TRACTOR and ancestry tracts were meta-analyzed using METAL. We replicated top associations in the independent ACCOuNT cohort of AAs (N=309) and validated associations in a warfarin pharmacokinetic study in AAs. To elucidate func

SUBMITTER: Singh A 

PROVIDER: S-EPMC11908343 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature