Pharmacogenomic genotypes define genetic ancestry in patients and enable population-specific genomic implementation.
Journal
The pharmacogenomics journal
ISSN: 1473-1150
Titre abrégé: Pharmacogenomics J
Pays: United States
ID NLM: 101083949
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
22
03
2018
accepted:
18
07
2019
revised:
02
05
2019
pubmed:
12
9
2019
medline:
5
1
2021
entrez:
12
9
2019
Statut:
ppublish
Résumé
The importance of genetic ancestry characterization is increasing in genomic implementation efforts, and clinical pharmacogenomic guidelines are being published that include population-specific recommendations. Our aim was to test the ability of focused clinical pharmacogenomic SNP panels to estimate individual genetic ancestry (IGA) and implement population-specific pharmacogenomic clinical decision-support (CDS) tools. Principle components and STRUCTURE were utilized to assess differences in genetic composition and estimate IGA among 1572 individuals from 1000 Genomes, two independent cohorts of Caucasians and African Americans (AAs), plus a real-world validation population of patients undergoing pharmacogenomic genotyping. We found that clinical pharmacogenomic SNP panels accurately estimate IGA compared to genome-wide genotyping and identify AAs with ≥70 African ancestry (sensitivity >82%, specificity >80%, PPV >95%, NPV >47%). We also validated a new AA-specific warfarin dosing algorithm for patients with ≥70% African ancestry and implemented it at our institution as a novel CDS tool. Consideration of IGA to develop an institutional CDS tool was accomplished to enable population-specific pharmacogenomic guidance at the point-of-care. These capabilities were immediately applied for guidance of warfarin dosing in AAs versus Caucasians, but also provide a real-world model that can be extended to other populations and drugs as actionable genomic evidence accumulates.
Identifiants
pubmed: 31506565
doi: 10.1038/s41397-019-0095-z
pii: 10.1038/s41397-019-0095-z
pmc: PMC7184888
mid: NIHMS1571370
doi:
Substances chimiques
Anticoagulants
0
Warfarin
5Q7ZVV76EI
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126-135Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL105198
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL123311
Pays : United States
Organisme : NIGMS NIH HHS
ID : K23 GM100288
Pays : United States
Organisme : NHLBI NIH HHS
ID : 1F32HL123311-01A1
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002387
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD010723
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK092949
Pays : United States
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