A paradigm shift in pharmacogenomics: From candidate polymorphisms to comprehensive sequencing.
Basic Clin Pharmacol Toxicol
; 131(6): 452-464, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35971800
ABSTRACT
Genetic factors have long been recognized as important determinants of interindividual variability in drug efficacy and toxicity. However, despite the increasing number of established gene-drug associations, candidate polymorphisms can only explain a fraction of the genetically encoded functional variability in drug disposition. Advancements in genetic profiling methods now allow to analyse the landscape of human pharmacogenetic variations comprehensively, which opens new opportunities to identify novel factors that could explain the "missing heritability." Here, we provide an updated overview of the landscape of pharmacogenomic variability based on recent analyses of population-scale sequencing projects. We then summarize the current state-of-the-art how the functional consequences of variants with unknown effects can be quantitatively estimated while discussing challenges and peculiarities that are specific to pharmacogenes. In the last sections, we discuss the importance of considering ethnogeographic diversity to provide equitable benefits of pharmacogenomics and summarize current roadblocks for the implementation of sequencing-based guidance of clinical decision-making. Based on the current state of the field, we conclude that testing is likely to gradually shift from the interrogation of selected candidate polymorphisms to comprehensive sequencing, which allows to consider the full spectrum of pharmacogenomic variations for a true personalization of genomic prescribing.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacogenética
/
Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Suécia