» Articles » PMID: 34291172

On the Path Towards Personalized Medicine: Implications of Pharmacogenetic Studies of Alcohol Use Disorder Medications

Overview
Date 2021 Jul 22
PMID 34291172
Citations 1
Authors
Affiliations
Soon will be listed here.
Abstract

Introduction: The heritability of alcohol use disorder (AUD) is estimated to be ~50%; however, the genetic basis of the disease is still poorly understood. The genetic variants identified thus far only explain a small percentage of AUD phenotypic variability. While genome-wide association studies (GWAS) are impacted by technical and methodological limitations, genetic variants that have been identified independently of GWAS findings can moderate the efficacy of AUD medications.

Areas Covered: This review discusses findings from clinical pharmacogenetic studies of AUD medications. While the pharmacogenetic studies reviewed involve several genetic variants in the major neurotransmitter systems, genetic loci in the opioid system have garnered the most attention.

Expert Opinion: The clinical utility of pharmacogenetics in AUD populations is uncertain at this time. There are several ongoing prospective clinical trials that will enhance knowledge regarding the applicability of pharmacogenetics in clinical populations. We recommend that future work in this area consider reverse translating from genotype to phenotype, mapping genes to stages of the addiction cycle, mapping genes to neural circuits, and harnessing large population-based cohorts.

Citing Articles

Synchrony between midbrain gene transcription and dopamine terminal regulation is modulated by chronic alcohol drinking.

Farahbakhsh Z, Holleran K, Sens J, Fordahl S, Mauterer M, Lopez A Nat Commun. 2025; 16(1):1944.

PMID: 39994195 PMC: 11850823. DOI: 10.1038/s41467-025-56715-y.


Translational models of addiction phenotypes to advance addiction pharmacotherapy.

Ray L, Nieto S, Grodin E Ann N Y Acad Sci. 2022; 1519(1):118-128.

PMID: 36385614 PMC: 10823887. DOI: 10.1111/nyas.14929.

References
1.
Ray L, Miranda Jr R, MacKillop J, McGeary J, Tidey J, Rohsenow D . A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers. Exp Clin Psychopharmacol. 2009; 17(2):122-9. PMC: 3682424. DOI: 10.1037/a0015700. View

2.
Gelernter J, Kranzler H, Sherva R, Almasy L, Koesterer R, Smith A . Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci. Mol Psychiatry. 2013; 19(1):41-9. PMC: 4165335. DOI: 10.1038/mp.2013.145. View

3.
Bauer L, Covault J, Harel O, Das S, Gelernter J, Anton R . Variation in GABRA2 predicts drinking behavior in project MATCH subjects. Alcohol Clin Exp Res. 2007; 31(11):1780-7. PMC: 3169387. DOI: 10.1111/j.1530-0277.2007.00517.x. View

4.
Mann K, Roos C, Hoffmann S, Nakovics H, Lemenager T, Heinz A . Precision Medicine in Alcohol Dependence: A Controlled Trial Testing Pharmacotherapy Response Among Reward and Relief Drinking Phenotypes. Neuropsychopharmacology. 2017; 43(4):891-899. PMC: 5809801. DOI: 10.1038/npp.2017.282. View

5.
Kranzler H, Zhou H, Kember R, Smith R, Justice A, Damrauer S . Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nat Commun. 2019; 10(1):1499. PMC: 6445072. DOI: 10.1038/s41467-019-09480-8. View