Local Ancestry-Informed Candidate Pathway Analysis of Warfarin Stable Dose in Latino Populations

Heidi E. Steiner, Kelvin Carrasquillo Carrion, Jason B. Giles, Abiel Roche Lima, Kevin Yee, Xiaoxiao Sun, Larisa H. Cavallari, Minoli A. Perera, Jorge Duconge, Jason H. Karnes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Accuracy of warfarin dose prediction algorithms may be improved by including data from diverse populations in genetic studies of dose variability. Here, we surveyed single nucleotide polymorphisms in vitamin K-related genetic pathways for association with warfarin dose requirements in two admixed Latino populations in standard-principal component adjusted and contemporary-local ancestry adjusted regression models. A total of five variants from vitamin K-related genes/pathways were associated with warfarin dose in both cohorts (P < 0.0125) in standard models. Local ancestry-adjusted analysis unveiled 35 associated variants with absolute effects ranging from β = 9.04 (±2.23) to 39.18 (±10.89) per ancestral allele in the discovery cohort and β = 6.47 (± 2.02) to 17.82 (± 6.83) in the replication cohort. Importantly, we demonstrate the technical validity of the Tractor model in cohorts with admixed ancestry from three founder populations and bring attention to the technical hurdles obstructing the inclusion of diverse, especially admixed, populations in pharmacogenomic research.

Original languageEnglish (US)
Pages (from-to)680-691
Number of pages12
JournalClinical pharmacology and therapeutics
Issue number3
StatePublished - Mar 2023

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


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