Richard C Crist1, Rachel Vickers-Smith2, Rachel L Kember1, Christopher T Rentsch3, Heng Xu4, E Jennifer Edelman5, Emily E Hartwell6, Kyle M Kampman1, Henry R Kranzler7. 1. Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, United States; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. 2. Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, United States; Department of Epidemiology, University of Kentucky College of Public Health, Lexington, KY 40536, United States; Center on Drug and Alcohol Research, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, KY 40536, United States. 3. VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT 06516, United States; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK. 4. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. 5. Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States. 6. Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, United States. 7. Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, United States; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: kranzler@pennmedicine.upenn.edu.
Abstract
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. Published by Elsevier B.V.
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. Published by Elsevier B.V.
Entities:
Keywords:
Buprenorphine; Genetics; Genome-wide association study; Opioid use disorder; Treatment predictors; Treatment response
Authors: Margaret T May; Amy C Justice; Kate Birnie; Suzanne M Ingle; Colette Smit; Colette Smith; Didier Neau; Marguerite Guiguet; Carolynne Schwarze-Zander; Santiago Moreno; Jodie L Guest; Antonella dʼArminio Monforte; Cristina Tural; Michael J Gill; Andrea Bregenzer; Ole Kirk; Michael Saag; Timothy R Sterling; Heidi M Crane; Jonathan A C Sterne Journal: J Acquir Immune Defic Syndr Date: 2015-07-01 Impact factor: 3.731
Authors: Jennifer S Potter; Elise N Marino; Maureen P Hillhouse; Suzanne Nielsen; Katharina Wiest; Catherine P Canamar; Judith A Martin; Alfonso Ang; Rachael Baker; Andrew J Saxon; Walter Ling Journal: J Stud Alcohol Drugs Date: 2013-07 Impact factor: 2.582
Authors: Liping Hou; Urs Heilbronner; Franziska Degenhardt; Mazda Adli; Kazufumi Akiyama; Nirmala Akula; Raffaella Ardau; Bárbara Arias; Lena Backlund; Claudio E M Banzato; Antoni Benabarre; Susanne Bengesser; Abesh Kumar Bhattacharjee; Joanna M Biernacka; Armin Birner; Clara Brichant-Petitjean; Elise T Bui; Pablo Cervantes; Guo-Bo Chen; Hsi-Chung Chen; Caterina Chillotti; Sven Cichon; Scott R Clark; Francesc Colom; David A Cousins; Cristiana Cruceanu; Piotr M Czerski; Clarissa R Dantas; Alexandre Dayer; Bruno Étain; Peter Falkai; Andreas J Forstner; Louise Frisén; Janice M Fullerton; Sébastien Gard; Julie S Garnham; Fernando S Goes; Paul Grof; Oliver Gruber; Ryota Hashimoto; Joanna Hauser; Stefan Herms; Per Hoffmann; Andrea Hofmann; Stephane Jamain; Esther Jiménez; Jean-Pierre Kahn; Layla Kassem; Sarah Kittel-Schneider; Sebastian Kliwicki; Barbara König; Ichiro Kusumi; Nina Lackner; Gonzalo Laje; Mikael Landén; Catharina Lavebratt; Marion Leboyer; Susan G Leckband; Carlos A López Jaramillo; Glenda MacQueen; Mirko Manchia; Lina Martinsson; Manuel Mattheisen; Michael J McCarthy; Susan L McElroy; Marina Mitjans; Francis M Mondimore; Palmiero Monteleone; Caroline M Nievergelt; Markus M Nöthen; Urban Ösby; Norio Ozaki; Roy H Perlis; Andrea Pfennig; Daniela Reich-Erkelenz; Guy A Rouleau; Peter R Schofield; K Oliver Schubert; Barbara W Schweizer; Florian Seemüller; Giovanni Severino; Tatyana Shekhtman; Paul D Shilling; Kazutaka Shimoda; Christian Simhandl; Claire M Slaney; Jordan W Smoller; Alessio Squassina; Thomas Stamm; Pavla Stopkova; Sarah K Tighe; Alfonso Tortorella; Gustavo Turecki; Julia Volkert; Stephanie Witt; Adam Wright; L Trevor Young; Peter P Zandi; James B Potash; J Raymond DePaulo; Michael Bauer; Eva Z Reininghaus; Tomas Novák; Jean-Michel Aubry; Mario Maj; Bernhard T Baune; Philip B Mitchell; Eduard Vieta; Mark A Frye; Janusz K Rybakowski; Po-Hsiu Kuo; Tadafumi Kato; Maria Grigoroiu-Serbanescu; Andreas Reif; Maria Del Zompo; Frank Bellivier; Martin Schalling; Naomi R Wray; John R Kelsoe; Martin Alda; Marcella Rietschel; Francis J McMahon; Thomas G Schulze Journal: Lancet Date: 2016-01-22 Impact factor: 79.321
Authors: Madeleine St Ville; Andrew W Bergen; James W Baurley; Joe D Bible; Christopher S McMahan Journal: Int J Environ Res Public Health Date: 2022-04-29 Impact factor: 4.614