PDF(Pubmed)
Abstract：
Since 1990, published addiction psychiatry articles have exceeded 11,495. 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 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, confirmation has been mixed and controversial. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs 1800497 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 (rs 1800497 C>T) and severe alcoholism. Additionally, the DRD2 rs1800497 is associated with suicide behaviors robustly at P=1.77 × 10-7. Furthermore, DNA polymorphic alleles underlying SUD with multiple substances were mapped via chromatin refolding, revealed that the DRD2 gene and associated polymorphism(s) was the top gene signal (DRD2, P=7.9 × 10-12). Additionally, based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being at least one determinant of Reward Deficiency Syndrome (RDS) first reported in the Royal Society of Medicine journaling 1996.
摘要：
自1990年以来，发表的成瘾精神病学文章已超过11,495篇。来自Blum等人的几个。显示了遗传成瘾风险严重性（GARS）测试在识别来自多物质和疼痛诊所的队列中奖励不足行为的风险方面的临床相关性，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，确认是混合和有争议的。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。GWAS对120万退伍军人的抑郁和自杀研究证实了Blum等人的第一项精神病学候选基因研究发现。1990年；次要DRD2等位基因之间存在显著关联，TaqA1(rs1800497C>T)和严重酒精中毒。此外,DRD2rs1800497与自杀行为密切相关，P=1.77×10-7。此外，具有多种物质的SUD基础的DNA多态性等位基因通过染色质重折叠定位，显示DRD2基因及其相关多态性是最高的基因信号（DRD2，P=7.9×10-12）。此外,基于这些调查，我们得出的结论是,GWAS应该结束关于DRD2基因至少是奖励缺乏综合征(RDS)的一个决定因素的争论,该基因在皇家医学会杂志1996上首次报道.
