Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case–Control Subjects

Abstract

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson’s χ2 test or Fisher’s exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings.

Genetic Addiction Risk and Psychological Profiling Analyses for “Preaddiction” Severity Index

“…Pearson's χ 2 test or Fisher's exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population's alcoholism prevalence revealed a significant detection [88]. It is relevant that while the GARS test does not actually stratify low, median, or high preaddiction status, the newly developed RDSQ29, which has been validated [117], could be utilized in combination with the GARS.…”

“…These alleles were proposed for a GARS panel in case-control studies, specifically for alcoholism (Table 1) [see ref. [88] for further explanation]. Other studies also demonstrated that this could be associated with the impulsivity and aggression of AUD patients.…”

“…The primary issue involves the question of whether there exists a mixed hypo-or hyper-dopaminergia in this population. One investigation by Blum et al [88] utilized GARS testing in 24 Caucasians ages 12-19 derived from families with RDS. It was found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially drug-seeking (95%) and alcohol-seeking (64%).…”

“…Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least AUD, Blum's group [88] applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy-Weinberg Equilibrium of each polymorphism in cases and controls.…”

A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy

“…The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population's alcoholism prevalence showed a significant detection. The OR results indicated significance for COMT, OPRM1, DRD2, DRD3, DRD4, DAT1, and 5HTT at 5% (Blum et al 2018 , 2020 , 2021 ; Blum et al 2022a , b ; Blum et al 2022a , b ; Fried et al 2020 ; Moran et al 2021 ; Bajaj et al 2022 ; Dennen et al 2022 ; Gondré-Lewis et al 2022 ; Gupta et al 2022 ; Vereczkei et al 2022 ; Thanos et al 2023a , b ; Thanos et al 2023a , b ). Consequently, this study aimed to explore the most effective pharmacogenomic approach to managing spinal pain in postoperative patients by analyzing potential actionable genetic variants associated with FDA-approved drugs targeting specific receptors, that is, the genes themselves (Table 2 ).…”