Local Ancestry-Informed Candidate Pathway Analysis of Warfarin Stable Dose in Latino Populations.
Clin Pharmacol Ther
; 113(3): 680-691, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36321873
ABSTRACT
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 ß = 9.04 ( ±2.23) to 39.18 ( ±10.89) per ancestral allele in the discovery cohort and ß = 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Varfarina
/
Anticoagulantes
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article