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

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 first published in JAMA (1990) concerning the association of the 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 rs 1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the 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 allele, Taq A1 (rs 1800497 C>T) and severe alcoholism. Additionally, the rs1800497 is associated with suicide behaviors robustly at P=1.77 × 10. Furthermore, DNA polymorphic alleles underlying SUD with multiple substances were mapped via chromatin refolding, revealed that the gene and associated polymorphism(s) was the top gene signal (DRD2, P=7.9 × 10). Additionally, based on these investigations, we conclude that GWAS should end the controversy about the gene being at least one determinant of Reward Deficiency Syndrome (RDS) first reported in the Royal Society of Medicine journaling 1996.