Kim Jee Wook, Choe Young Min, Shin Joong-Gon, Park Byung Lae, Shin Hyung-Doo, Choi Ihn-Geun, Lee Boung Chul
Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi Province, Republic of Korea.
Department of Psychiatry, Hallym University College of Medicine, Chuncheon, Republic of Korea,
Neuropsychiatr Dis Treat. 2018 Dec 24;15:83-94. doi: 10.2147/NDT.S184067. eCollection 2019.
Alcohol dependence (AD) is a common disorder that is influenced by genetic as well as environmental factors. A previous genome-wide association study (GWAS) of the Korean population performed by our research group identified a number of genes, including () and (), as novel genetic markers of AD.
The present investigation was a fine-mapping follow-up study of 459 AD and 455 non-AD subjects of Korean descent to determine the associations between and polymorphisms and AD. The Alcohol Use Disorders Identification Test (AUDIT) was administered to screen for the degree of AD risk in the subjects and 58 genetic variants, 5 for and 53 for , were genotyped for subsequent association analyses.
In the present case-control analysis, showed the most significant association signal with a risk of AD (=1.29×10, =7.74×10, OR =0.19). There were also significant differences in the overall and subcategory scores for the genetic variants, including (=9.94×10, =5.96×10 at for the overall AUDIT score). However, the genetic effects of polymorphisms observed in our previous GWAS were not replicated in the present study (minimum =0.0005, >0.05, OR =0.30 at in the recessive model). Furthermore, the single-nucleotide polymorphisms of were not associated with the overall and subcategory AUDIT scores.
The present findings suggest that the genetic variants of may contribute to a predisposition for an alcohol use disorder.
酒精依赖（AD）是一种常见的疾病，受遗传和环境因素影响。我们研究小组对韩国人群进行的一项全基因组关联研究（GWAS）确定了许多基因，包括（）和（），作为AD的新型遗传标记。
本研究是一项精细定位的随访研究，对459名韩国裔AD患者和455名非AD患者进行，以确定与多态性和AD之间的关联。采用酒精使用障碍识别测试（AUDIT）对受试者的AD风险程度进行筛查，并对58个基因变异进行基因分型，其中5个为基因变异，53个为基因变异，用于后续的关联分析。
在本病例对照分析中，与AD风险显示出最显著的关联信号（=1.29×10，=7.74×10，OR =0.19）。基因变异的总体和亚类评分也存在显著差异，包括（总体AUDIT评分为时，=9.94×10，=5.96×10）。然而，我们之前GWAS中观察到的多态性的遗传效应在本研究中未得到重复（隐性模型中，最小=0.0005，>0.05，OR =0.30）。此外，的单核苷酸多态性与总体和亚类AUDIT评分无关。
本研究结果表明，的基因变异可能导致酒精使用障碍的易感性。
