Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

Blum K,Downs Bw,Brewer R,Hauser M,Badgaiyan Rd,Boyett B,Siwicki D,Badgaiyan S,Lott L,Fried L,Baron D,Bowirrat A,Gondre-Lewis Mc,Roy A,Smith De,Panayotis K Thanos,Ponce Jv

doi:10.15761/jsin.1000221

Abstract

Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum’s group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case –controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of 110,241 cases and 122,525 controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case –control studies indicating selective association of these risk alleles ( measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data –a work in progress.

Highlights

History of Reward Deficiency Syndrome (RDS) developmentResearch into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) [1] includes all drug and non-drug addictive, obsessive and compulsive behaviors
A review of the related Figure 3 strongly suggest that while we may take argument concerning many of these so-called controls it is quite remarkable that there are a plethora of case –control studies indicating selective association of these risk alleles for the most part indicating a hypodopaminergia
The DAT1 variable number of tandem repeats (VNTR) was significantly associated with alcoholism in Badaga Genotyped the VNTR of DAT1 gene in a sample population but not in Kota population. of N=206 subjects from the Kota population Our results suggest that the A9 (111 alcohol dependence cases and 95 controls) allele of the DAT gene is involved and N=142 subjects from Badaga population (81 in vulnerability to alcoholism, but alcohol dependence cases and 61 controls). that these associations are population specific

Summary

Introduction

History of Reward Deficiency Syndrome (RDS) development. Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) [1] includes all drug and non-drug addictive, obsessive and compulsive behaviors. Research directed toward improving treatment for highly drugdependent patients in underserved populations represents one example of adoption of this bold concept and is under study through a NIH grant [3]. The grant explores utilization of the Genetic Addiction Risk Score (GARS) and the neuronutrient pro-dopamine regulator KB220. The development of GARS followed seminal research in 1990, whereby, Blum’s group identified the first genetic association with severe alcoholism published in JAMA [4]. The non-invasive GARS test identifies and measures the total number of risk alleles of genes and catabolic enzymes affecting an individual's neurochemical hypodopaminergic function and has been associated in hundreds of studies with SUD [5]

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Conclusion