# Pharmacogenetic Study of Opioid Agonist Treatments in MVP

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2021 · —

## Abstract

1. Objectives: In the US, opioids are widely used for maintenance treatment of opioid use
 disorder (OUD) and to manage acute and chronic pain. Over the past three decades,
 efforts to treat pain aggressively in the absence of objective markers to guide opioid
 prescribing have led to a quadrupling of opioid prescriptions, an epidemic of opioid
 misuse and abuse, and a tripling of the overdose death rate in the general population
 and among Veterans. The overarching objective of this proposal is to identify valid
 biomarkers of opioid sensitivity, which can be used to guide the safe and effective
 use of opioid agonists to treat both OUD and pain. Following the identification of
 pharmacogenetic predictors, we will validate the findings in an independent MVP
 sample. The findings will inform the treatment of OUD using buprenorphine and the
 management of acute and chronic pain with prescription opioids.
2. Research Design: We will conduct a series of genome-wide association studies
 (GWASs) using data from the Million Veteran Program (MVP). The initial GWAS will
 be conducted in the ~300,000 Veterans for whom GWAS data are currently
 available; genotypes from ~100,000 newly recruited participants will be used to
 replicate the initial findings.
3. Methodology: We will conduct separate GWASs of: 1) the effectiveness and dosing of
 buprenorphine maintenance, using urine drug screen data and VA pharmacy dosing
 records; 2) mean maximal morphine equivalent dose (MEDD) in treating acute pain in
 the perioperative period, separately for different classes of opioids, using inpatient
 pharmacy records for Veterans who have undergone hip or knee arthroplasty; and 3)
 opioid analgesic dosing for the treatment of chronic pain, using outpatient pharmacy
 records to estimate mean MEDD for the month of heaviest opioid use. Analyses will
 also be run both separately by opioid class (followed by meta-analysis) and with
 longitudinal trajectories of opioid use. Regression analyses will examine the
 proportion of urine tests positive for opioids and usual daily dosage of buprenorphine for
 maintenance, mean maximal MEDD in inpatient analyses, and MEDD and opioid use
 trajectories in outpatient analyses. Imputed minor allele dosage, age, body weight, sex,
 and the top ancestry principal components will serve as covariates, along with
 covariates relevant to each of the specific aims. We will conduct all GWAS analyses
 separately by population group and combine the results by meta-analysis. Polygenic
 risk score (PRS) analysis will serve to increase the utility of the GWAS findings.
4. Impact/Significance: The identification and validation of genetic variants and PRS
 scores will be used to generate indices that can be evaluated prospectively as
 guides to prescribers in their selection of the optimal opioid agonist and dosage for
 buprenorphine maintenance and opioid analgesia. Personalizing the treatment of OUD
 can increase its effectiveness and reduce relapse ri...

## Key facts

- **NIH application ID:** 9890783
- **Project number:** 5I01CX001734-02
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** KYLE Matthew KAMPMAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890783

## Citation

> US National Institutes of Health, RePORTER application 9890783, Pharmacogenetic Study of Opioid Agonist Treatments in MVP (5I01CX001734-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9890783. Licensed CC0.

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