On the path towards personalized medicine: Implications of pharmacogenetic studies of alcohol use disorder medications.
On the path towards personalized medicine: Implications of pharmacogenetic studies of alcohol use disorder medications.
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DOI：
10.1080/23808993.2020.1724510
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发表时间：
2020
影响因子：
1.2
通讯作者：
Ray LA
中科院分区：
文献类型：
--
作者：
Nieto SJ;Grodin EN;Ray LA
酒精使用障碍（AUD）的遗传率估计约为50%;然而，该疾病的遗传基础仍然知之甚少。到目前为止，鉴定的遗传变异仅解释了一小部分AUD表型变异。虽然全基因组关联研究（GWAS）受到技术和方法学限制的影响，但独立于GWAS发现的遗传变异可能会降低AUD药物的疗效。本文综述了AUD药物的临床药物遗传学研究结果。虽然回顾的药物遗传学研究涉及主要神经递质系统中的几种遗传变异，但阿片系统中的遗传位点引起了最多的关注。目前尚不确定药物遗传学在AUD人群中的临床效用。有几个正在进行的前瞻性临床试验，将提高有关药物遗传学在临床人群中的适用性的知识。我们建议在这一领域的未来工作考虑从基因型到表型的反向转换，将基因映射到成瘾周期的各个阶段，将基因映射到神经回路，并利用大量基于人群的队列。
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. 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. 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.