PDF(Pubmed)
Abstract：
Since 1990, there have been thousands of published studies on addiction psychiatry. Several from Blum et al showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance abuse and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, reactions have been mixed. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al 1990; a significant association between the minor DRD2 allele, Taq A1 and severe alcoholism. Additionally, the DRD2 rs1800497 is robustly associated with suicidal behaviors. Furthermore, DNA polymorphic alleles underlying substance use disorder (SUD) with multiple substances were mapped via chromatin refolding, revealing that the DRD2 gene and associated polymorphism(s) as the top gene signal. Based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being one determinant of Reward Deficiency Syndrome (RDS) first reported in 1996.
摘要：
自1990年以来，已有数千项关于成瘾精神病学的研究发表。Blum等人的一些研究表明，遗传成瘾风险严重性（GARS）测试在识别来自多物质滥用和疼痛诊所的队列中奖励不足行为的风险方面具有临床相关性。手术后的心脏病科，和DWI罪犯面临牢狱之灾。自从Blum等人首次发表在JAMA（1990）关于DRD2基因多态性与严重酒精中毒的关联，反应参差不齐。最近,然而,一项包含62项研究的荟萃分析显示,DRD2rs1800497与酒精使用障碍(AUD)之间存在显著关联.耶鲁大学的其他研究表明，DRD2基因A1等位基因的单倍型阻断与AUD和海洛因依赖有关。对120万退伍军人的抑郁症和自杀的GWAS研究证实了Blum等1990年的第一个精神病学候选基因研究发现;次要DRD2等位基因之间的显着关联，TaqA1和严重的酒精中毒。此外,DRD2rs1800497与自杀行为密切相关.此外，通过染色质重折叠定位了具有多种物质的物质使用障碍（SUD）的DNA多态性等位基因，揭示了DRD2基因和相关的多态性（S）作为顶部基因信号。根据这些调查,我们得出的结论是，GWAS应该结束关于DRD2基因是1996年首次报道的奖励缺乏综合征（RDS）的决定因素的争议。
