Genetic contributions to alcohol use disorder treatment outcomes

• Verfasst von: Biernacka, Joanna [VerfasserIn]
• Verfasst von: Coombes, Brandon J. [VerfasserIn]
• Verfasst von: Batzler, Anthony [VerfasserIn]
• Verfasst von: Ho, Ada Man-Choi [VerfasserIn]
• Verfasst von: Geske, Jennifer R. [VerfasserIn]
• Verfasst von: Frank, Josef [VerfasserIn]
• Verfasst von: Hodgkinson, Colin [VerfasserIn]
• Verfasst von: Skime, Michelle [VerfasserIn]
• Verfasst von: Colby, Colin [VerfasserIn]
• Verfasst von: Zillich, Lea [VerfasserIn]
• Verfasst von: Pozsonyiova, Sofia [VerfasserIn]
• Verfasst von: Ho, Ming-Fen [VerfasserIn]
• Verfasst von: Kiefer, Falk [VerfasserIn]
• Verfasst von: Rietschel, Marcella [VerfasserIn]
• Verfasst von: Weinshilboum, Richard [VerfasserIn]
• Verfasst von: O’Malley, Stephanie S. [VerfasserIn]
• Verfasst von: Mann, Karl [VerfasserIn]
• Verfasst von: Anton, Ray [VerfasserIn]
• Verfasst von: Goldman, David [VerfasserIn]
• Verfasst von: Karpyak, Victor M. [VerfasserIn]
• Titel: Genetic contributions to alcohol use disorder treatment outcomes
• Titelzusatz: a genome-wide pharmacogenomics study
• Verf.angabe: Joanna M. Biernacka, Brandon J. Coombes, Anthony Batzler, Ada Man-Choi Ho, Jennifer R. Geske, Josef Frank, Colin Hodgkinson, Michelle Skime, Colin Colby, Lea Zillich, Sofia Pozsonyiova, Ming-Fen Ho, Falk Kiefer, Marcella Rietschel, Richard Weinshilboum, Stephanie S. O’Malley, Karl Mann, Ray Anton, David Goldman and Victor M. Karpyak
• E-Jahr: 2021
• Jahr: 23 July 2021
• Umfang: 8 S.
• Fussnoten: Published online: 23 July 2021 ; Gesehen am 14.12.2022
• Titel Quelle: Enthalten in: Neuropsychopharmacology
• Ort Quelle: London : Springer Nature, 1993
• Jahr Quelle: 2021
• Band/Heft Quelle: 46(2021), 12, Seite 2132-2139
• ISSN Quelle: 1740-634X
• DOI: doi:10.1038/s41386-021-01097-0
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Behavioural genetics
• Sach-SW: Predictive markers
• K10plus-PPN: 1827010630

Abstract

Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥ 5 drinks for men, ≥4 drinks for women in a day), during the first 3 months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N = 1083 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p = 1.6E−8) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p = 3.9E−8; acamprosate TR: rs77583603, p = 3.1E−9). The top association signal for TR (p = 7.7E−8) and second strongest signal in the THR (p = 6.1E−8) analysis of naltrexone-treated patients maps to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p = 3.7E−4) and THR (p = 2.6E−4). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.