Background: The search for an accurate, gene-based test to identify heritable risk
factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published
studies about the role of dopamine in addictive behaviors, including risk for drug dependence
and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum’s group
in 1995 to identify a group of behaviors with a common neurobiological mechanism associated
with a polymorphic allelic propensity for hypodopaminergia.
Objectives: To outline the process used to select risk alleles of reward genes for the Genetic
Addiction Risk Score (GARS) test. Consequently, to address the limitations caused by inconsistent
results that occur in many case-control behavioral association studies. These limitations
are perhaps due to the failure of investigators to adequately screen controls for drug and alcohol
use disorder, and any of the many RDS behaviors, including nicotine dependence, obesity,
pathological gambling, and internet gaming addiction.
Methods: Review of the literature related to the function of risk alleles of reward genes associated
with hypodopaminergia relevant case-control association studies for the selection of alleles
to be measured by the Genetic Addiction Risk Score (GARS) test.
Results: The prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to
“Super-Controls” [highly screened RDS controls (3.3%) in proband and family] is used to exemplify
a possible solution.
Conclusion: Unlike One Gene-One Disease (OGOD), RDS is polygenetic, and very complex.
In addition, any RDS-related behaviors must be eliminated from the control group in order to
obtain the best possible statistical analysis instead of comparing the phenotype with diseaseridden