Evidence for the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS).

Clinical and experimental psychology Pub Date : 2023-06-29
Kenneth Blum, Abdala Bowirrat, Igor Elman, David Baron, Panayotis K Thanos, Mark S Gold, Colin Hanna, Milan T Makale, Keerthy Sunder, Nicole Jafari, Foojan Zeine, Kevin T Murphy, Miles Makale, Rajendra D Badgaiyan
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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.

Abstract Image

DRD2基因作为奖励缺乏综合征(RDS)决定因素的证据。
自1990年以来,发表的成瘾精神病学文章已超过11495篇。Blum等人的几项研究显示了遗传成瘾风险严重程度(GARS)测试在识别来自多物质和疼痛诊所、术后减肥患者和面临监禁的酒后驾车罪犯的奖励缺乏行为风险方面的临床相关性。自Blum等人于1990年首次在JAMA上发表关于DRD2基因多态性与严重酒精中毒的关联的文章以来,对其的证实一直存在分歧和争议。然而,最近一项对62项研究的荟萃分析显示,DRD2 rs 1800497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滞与AUD和海洛因依赖有关。GWAS对120万退伍军人的抑郁和自杀的研究证实了Blum等人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taqa1 (rs 1800497 C>T)与严重酒精中毒之间存在显著关联。此外,DRD2 rs1800497与自杀行为显著相关(P=1.77 × 10-7)。此外,通过染色质重折叠定位了与SUD相关的多物质DNA多态性等位基因,发现DRD2基因及其相关多态性(s)是顶级基因信号(DRD2, P=7.9 × 10-12)。此外,基于这些研究,我们得出结论,GWAS应该结束关于DRD2基因是奖励缺乏综合征(RDS)的至少一个决定因素的争议,该争议首次在1996年英国皇家医学学会杂志上报道。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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