Pharmacogenetics at Scale: An Analysis of the UK Biobank.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
10
07
2020
accepted:
22
10
2020
pubmed:
26
11
2020
medline:
11
9
2021
entrez:
25
11
2020
Statut:
ppublish
Résumé
Pharmacogenetics (PGx) studies the influence of genetic variation on drug response. Clinically actionable associations inform guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), but the broad impact of genetic variation on entire populations is not well understood. We analyzed PGx allele and phenotype frequencies for 487,409 participants in the UK Biobank, the largest PGx study to date. For 14 CPIC pharmacogenes known to influence human drug response, we find that 99.5% of individuals may have an atypical response to at least 1 drug; on average they may have an atypical response to 10.3 drugs. Nearly 24% of participants have been prescribed a drug for which they are predicted to have an atypical response. Non-European populations carry a greater frequency of variants that are predicted to be functionally deleterious; many of these are not captured by current PGx allele definitions. Strategies for detecting and interpreting rare variation will be critical for enabling broad application of pharmacogenetics.
Identifiants
pubmed: 33237584
doi: 10.1002/cpt.2122
pmc: PMC8144239
mid: NIHMS1650377
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1528-1537Subventions
Organisme : NHGRI NIH HHS
ID : U24 HG010615
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM102365
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NLM NIH HHS
ID : T32 LM012409
Pays : United States
Organisme : Stanford University
Organisme : NIGMS NIH HHS
ID : U01 GM061374
Pays : United States
Informations de copyright
© 2020 The Author Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
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