Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty Article Swipe
Zeal Jinwala
,
Christal N. Davis
,
Jackson F SooHoo
,
Joel Gelernter
,
Rachel L. Kember
,
Rachel Vickers‐Smith
,
Henry R. Kranzler
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.23.25331996
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.23.25331996
Opioid analgesics are commonly prescribed to manage acute postoperative pain. However, individuals vary in their opioid dosing needs, with no validated biomarkers to guide prescribing. We used electronic health records data from the Million Veteran Program sample to investigate individual differences in opioid analgesic dosing following knee (n=18,540) or hip (n=9,363) arthroplasty in a predominantly male (93%) veteran sample. We extracted data from pharmacy records on inpatient opioid medications dispensed to estimate each patient’s average daily morphine milligram equivalent (MME) doses. We used genome-wide association studies (GWAS) stratified by arthroplasty type (i.e., knee or hip) and genetically inferred ancestry group (i.e., European-like (EUR), African-like (AFR), and Admixed American-like (AMR) to identify genetic variants associated with daily MME doses. Within-ancestry summary statistics from the knee and hip arthroplasty GWAS were meta-analyzed, followed by a cross-ancestry GWAS meta-analysis. We identified two genome-wide significant loci in the AFR hip arthroplasty GWAS and three in the AMR GWAS, through no variants were genome-wide significant in the cross-ancestry meta-analysis. Genes mapped to these loci were implicated in a wide range of biological functions, including T-cell activation, chromatin organization and epigenetic regulation, epidermal differentiation and cell adhesion, and cell growth and organ development. Tissue enrichment analysis revealed significant enrichment in brain tissue from early infancy developmental stage. This study provides a proof-of-concept framework for the use of electronic health records data to examine the genetics of opioid dosing in the management of post-operative pain. Summary Using electronic health record data from the Million Veteran Program, we identified genetic variants associated with opioid dosing needs following knee and hip arthroplasty procedures.
Related Topics
Concepts
Dosing
Medicine
Arthroplasty
Hip arthroplasty
Opioid
Hip pain
Genome-wide association study
Physical therapy
Internal medicine
Surgery
Biology
Genotype
Genetics
Gene
Single-nucleotide polymorphism
Receptor
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.07.23.25331996
- https://www.medrxiv.org/content/medrxiv/early/2025/07/24/2025.07.23.25331996.full.pdf
- OA Status
- green
- References
- 50
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412652627
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412652627Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.07.23.25331996Digital Object Identifier
- Title
-
Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip ArthroplastyWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-07-24Full publication date if available
- Authors
-
Zeal Jinwala, Christal N. Davis, Jackson F SooHoo, Joel Gelernter, Rachel L. Kember, Rachel Vickers‐Smith, Henry R. KranzlerList of authors in order
- Landing page
-
https://doi.org/10.1101/2025.07.23.25331996Publisher landing page
- PDF URL
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https://www.medrxiv.org/content/medrxiv/early/2025/07/24/2025.07.23.25331996.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
- OA URL
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https://www.medrxiv.org/content/medrxiv/early/2025/07/24/2025.07.23.25331996.full.pdfDirect OA link when available
- Concepts
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Dosing, Medicine, Arthroplasty, Hip arthroplasty, Opioid, Hip pain, Genome-wide association study, Physical therapy, Internal medicine, Surgery, Biology, Genotype, Genetics, Gene, Single-nucleotide polymorphism, ReceptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
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50Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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