Evidence map›Paper›PMID 36167815›Full record

ArticlePediatric research2023

Pharmacogenetic profiling via genome sequencing in children with medical complexity.

Amy Pan, Sierra Scodellaro, Tayyaba Khan, Inna Ushcatz, Wendy Wu, Meredith Curtis, Eyal Cohen, Ronald D Cohn, Robin Z Hayeems, M Stephen Meyn and 8 more

Open access · hybridFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

Amy PanGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Sierra ScodellaroProgram in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Tayyaba KhanGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Inna UshcatzGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Wendy WuGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Meredith CurtisGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Eyal CohenDepartment of Paediatrics, University of Toronto, Toronto, ON, Canada.
Ronald D CohnGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Robin Z HayeemsChild Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
M Stephen MeynDepartment of Paediatrics, University of Toronto, Toronto, ON, Canada.
Julia OrkinDepartment of Paediatrics, University of Toronto, Toronto, ON, Canada.
Jaskiran OtalDivision of Paediatric Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Miriam S ReuterThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Susan WalkerThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Stephen W SchererGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Christian R MarshallCentre for Genetic Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Iris CohnProgram in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Gregory CostainGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada. gregory.costain@sickkids.ca.
Hospital for Sick Children · CAUniversity of Toronto · CASickKids Foundation · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChildren with medical complexity (CMC) are a priority pediatric population, with high resource use and associated costs. Genome-wide sequencing is increasingly organized for CMC early in life as a diagnostic test. Polypharmacy becomes common as CMC age. Clinically relevant pharmacogenetic (PGx) information can be extracted from existing genome sequencing (GS) data via GS-PGx profiling. The role of GS-PGx profiling in the CMC population is unclear.

methodsPrescribed medications were extracted from care plans of 802 eligible CMC enrolled in a structured Complex Care Program over a 10-year period. Drug-gene associations were annotated using curated Clinical Pharmacogenetics Implementation Consortium data. GS-PGx profiling was then performed for a subset of 50 CMC.

resultsOverall, 546 CMC (68%) were prescribed at least one medication with an established PGx association. In the GS-PGx subgroup, 24 (48%) carried variants in pharmacogenes with drug-gene guidelines for one or more of their current medications. All had findings of potential relevance to some medications, including 32 (64%) with variants in CYP2C19 that could affect their metabolism of proton-pump inhibitors.

conclusionGS-PGx profiling at the time of diagnostics-focused genetic testing could be an efficient way to incorporate precision prescribing practices into the lifelong care of CMC. IMPACT: Polypharmacy and genetic test utilization are both common in children with medical complexity. The role of repurposing genome sequencing data for pharmacogenetic profiling in children with medical complexity was previously unclear. We identified a high rate of medication use with clinically relevant drug-gene associations in this priority pediatric population and demonstrated that relevant pharmacogenetic information can be extracted from their existing genome sequencing data. Pharmacogenetic profiling at the time of diagnostics-focused genetic testing could be an efficient way to incorporate precision prescribing practices into the lifelong care of children with medical complexity.

Indexed as

Genetic TestingPharmacogeneticsChildChromosome MappingHumans

Identifiers

PMID36167815
PMCPMC10033400
OpenAlexW4297231491

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read24
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.