On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications

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 considers 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.

KEYWORDS:

• Alcohol
• pharmacogenetics
• precision medicine
• drug development
• alcohol use disorder

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism to SJN (F31AA026495), ENG (F32AA027699), and LAR (K24AA025704).