Analysis of genetic and clinical factors associated with buprenorphine response

Richard C. Crist, Rachel Vickers-Smith, Rachel L. Kember, Christopher T. Rentsch, Heng Xu, E. Jennifer Edelman, Emily E. Hartwell, Kyle M. Kampman, Henry R. Kranzler

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Buprenorphine, approved for treating opioid use disorder (OUD), is not equally efficacious for all patients. Candidate gene studies have shown limited success in identifying genetic moderators of buprenorphine treatment response. Methods: We studied 1616 European-ancestry individuals enrolled in the Million Veteran Program, of whom 1609 had an ICD-9/10 code consistent with OUD, a 180-day buprenorphine treatment exposure, and genome-wide genotype data. We conducted a genome-wide association study (GWAS) of buprenorphine treatment response [defined as having no opioid-positive urine drug screens (UDS) following the first prescription]. We also examined correlates of buprenorphine treatment response in multivariable analyses. Results: Although no variants reached genome-wide significance, 6 loci were nominally significant (p < 1 × 10−5), four of which were located near previously characterized genes: rs756770 (ADAMTSL2), rs11782370 (SLC25A37), rs7205113 (CRISPLD2), and rs13169373 (LINC01947). A higher maximum daily buprenorphine dosage (aOR = 0.98; 95 %CI: 0.97, 0.995), greater number of UDS (aOR = 0.97; 95 %CI: 0.96, 0.99), and history of hepatitis C (HCV) infection (aOR = 0.71; 95 %CI: 0.57, 0.88) were associated with a reduced odds of buprenorphine response. Older age (aOR: 1.01; 95 %CI: 1.000, 1.02) was associated with increased odds of buprenorphine response. Conclusions: This study had limited statistical power to detect genetic variants associated with a complex human phenotype like buprenorphine treatment response. Meta-analysis of multiple data sets is needed to ensure adequate statistical power for a GWAS of buprenorphine treatment response. The most robust phenotypic predictor of buprenorphine treatment response was intravenous drug use, a proxy for which was HCV infection.

Original languageEnglish
Article number109013
JournalDrug and Alcohol Dependence
StatePublished - Oct 1 2021

Bibliographical note

Funding Information:
This research is based on data from the Million Veteran Program (MVP), Office of Research and Development, Veterans Health Administration, and was supported by award #I01 CX001734-01 (MVP012); the Veterans Integrated Service Network 4 Mental Illness Research, Education and Clinical Center ; and P30 DA046345 from the National Institute on Drug Abuse . This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

Publisher Copyright:
© 2021


  • Buprenorphine
  • Genetics
  • Genome-wide association study
  • Opioid use disorder
  • Treatment predictors
  • Treatment response

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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