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Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty.

作者信息

Jinwala Zeal, Davis Christal N, SooHoo Jackson F, Gelernter Joel, Kember Rachel L, Vickers-Smith Rachel, Kranzler Henry R

机构信息

Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.

Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

出版信息

Res Sq. 2025 Aug 21:rs.3.rs-7330342. doi: 10.21203/rs.3.rs-7330342/v1.


DOI:10.21203/rs.3.rs-7330342/v1
PMID:40894051
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12393474/
Abstract

Opioids 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 (EHR) 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. We extracted data from pharmacy records on inpatient opioid medications to estimate average daily morphine milligram equivalent (MME) dosages and used genome-wide association studies (GWAS) to identify genetic variants associated with daily MME dosage, followed by a cross-ancestry and cross-phenotype meta-analysis. We identified two genome-wide significant loci in the African ancestry knee arthroplasty GWAS and three in the Admixed-American ancestry hip arthroplasty GWAS. Multiple other loci in African, Admixed-American, and European populations were nominally significant. The study provides a framework for the use of EHR data to examine the genetics of opioid dosing in post-operative care.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3943/12393474/f322610d2170/nihpp-rs7330342v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3943/12393474/80afd1e827aa/nihpp-rs7330342v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3943/12393474/f322610d2170/nihpp-rs7330342v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3943/12393474/80afd1e827aa/nihpp-rs7330342v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3943/12393474/f322610d2170/nihpp-rs7330342v1-f0002.jpg

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[1]
Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty.

Res Sq. 2025-8-21

[2]
Multi-ancestry Genome-wide Association Study of Inpatient Opioid Dosing Following Knee or Hip Arthroplasty.

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[8]
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本文引用的文献

[1]
Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice.

Nat Commun. 2025-3-4

[2]
Distribution of opioid analgesics by community racial/ethnic and socioeconomic profiles, 2011-2021.

Pain. 2025-1-21

[3]
Expression of the Hippo pathway effector, TEAD1, within the developing murine forebrain.

Gene Expr Patterns. 2024-12

[4]
The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity.

Nucleic Acids Res. 2025-1-6

[5]
A genome-wide Association study of the Count of Codeine prescriptions.

Sci Rep. 2024-10-1

[6]
Synaptic sensitization in the anterior cingulate cortex sustains the consciousness of pain via synchronized oscillating electromagnetic waves.

Front Hum Neurosci. 2024-9-11

[7]
Trends in Opioid Prescribing and New Persistent Opioid Use After Surgery in the United States.

Ann Surg. 2025-3-1

[8]
Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits.

Neuropsychopharmacology. 2024-12

[9]
The functional and psychological impact of delayed hip and knee arthroplasty: a systematic review and meta-analysis of 89,996 patients.

Sci Rep. 2024-4-5

[10]
A multi-ancestry genetic study of pain intensity in 598,339 veterans.

Nat Med. 2024-4

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