Pharmacogenetic analysis of structural variation in the 1000 genomes project using whole genome sequences.
Next-generation sequencing
Pharmacogenetics
Population genetics
Star alleles
Structural variation
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
received:
25
04
2024
accepted:
20
09
2024
medline:
2
10
2024
pubmed:
2
10
2024
entrez:
1
10
2024
Statut:
epublish
Résumé
While significant strides have been made in understanding pharmacogenetics (PGx) and gene-drug interactions, there remains limited characterization of population-level PGx variation. This study aims to comprehensively profile global star alleles (haplotype patterns) and phenotype frequencies in 58 pharmacogenes associated with drug absorption, distribution, metabolism, and excretion. PyPGx, a star-allele calling tool, was employed to identify star alleles within high-coverage whole genome sequencing (WGS) data from the 1000 Genomes Project (N = 2504; 26 global populations). This process involved detecting structural variants (SVs), such as gene deletions, duplications, hybrids, as well as single nucleotide variants and insertion-deletion variants. The majority of our PyPGx calls for star alleles and phenotype frequencies aligned with the Pharmacogenomics Knowledge Base, although notable population-specific frequencies differed at least twofold. Validation efforts confirmed known SVs while uncovering several novel SVs currently undefined as star alleles. Additionally, we identified 210 small nucleotide variants associated with severe functional consequences that are not defined as star alleles. The study serves as a valuable resource, providing updated population-level star allele and phenotype frequencies while incorporating SVs. It also highlights the burgeoning potential of cost-effective WGS for PGx genotyping, offering invaluable insights to improve tailored drug therapies across diverse populations.
Identifiants
pubmed: 39354004
doi: 10.1038/s41598-024-73748-3
pii: 10.1038/s41598-024-73748-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22774Subventions
Organisme : NIH HHS
ID : R35HG011319
Pays : United States
Informations de copyright
© 2024. The Author(s).
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