"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS)

doi:10.2147/PRBM.S428841

. 2023 Oct 20:16:4287-4291.

doi: 10.2147/PRBM.S428841. eCollection 2023.

"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS)

Kenneth Blum^{1

2

3

4

5}, Panayotis K Thanos⁶, Colin Hanna⁶, Mark S Gold⁷, David Baron², Igor Elman⁸

Affiliations

¹ Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
² Division of Addiction Research & Education, Center for Exercise Sports, Mental Health, Western University Health Sciences, Pomona, CA, USA.
³ Institute of Psychology, Eötvös Loránd University Budapest, Budapest, Hungary.
⁴ Department of Psychiatry, Boonshoft School of Medicine, Wright University, Dayton, OH, USA.
⁵ Department of Psychiatry, Human Integrated Services Unit, University of Vermont Center for Clinical & Translational Science, College of Medicine, Burlington, VT, USA.
⁶ Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA.
⁷ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Department of Psychiatry, Harvard University College of Medicine, Cambridge, MA, USA.

PMID: 37885829
PMCID: PMC10597772
DOI: 10.2147/PRBM.S428841

"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS)

Kenneth Blum et al. Psychol Res Behav Manag. 2023.

. 2023 Oct 20:16:4287-4291.

doi: 10.2147/PRBM.S428841. eCollection 2023.

Authors

Kenneth Blum^{1

2

3

4

5}, Panayotis K Thanos⁶, Colin Hanna⁶, Mark S Gold⁷, David Baron², Igor Elman⁸

Affiliations

¹ Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
² Division of Addiction Research & Education, Center for Exercise Sports, Mental Health, Western University Health Sciences, Pomona, CA, USA.
³ Institute of Psychology, Eötvös Loránd University Budapest, Budapest, Hungary.
⁴ Department of Psychiatry, Boonshoft School of Medicine, Wright University, Dayton, OH, USA.
⁵ Department of Psychiatry, Human Integrated Services Unit, University of Vermont Center for Clinical & Translational Science, College of Medicine, Burlington, VT, USA.
⁶ Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA.
⁷ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Department of Psychiatry, Harvard University College of Medicine, Cambridge, MA, USA.

PMID: 37885829
PMCID: PMC10597772
DOI: 10.2147/PRBM.S428841

Abstract

Since 1990, there have been thousands of published studies on addiction psychiatry. 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 abuse 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, reactions have been mixed. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs1800497 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 and severe alcoholism. Additionally, the DRD2 rs1800497 is robustly associated with suicidal behaviors. Furthermore, DNA polymorphic alleles underlying substance use disorder (SUD) with multiple substances were mapped via chromatin refolding, revealing that the DRD2 gene and associated polymorphism(s) as the top gene signal. Based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being one determinant of Reward Deficiency Syndrome (RDS) first reported in 1996.

Keywords: DRD2 gene; GWAS; addictive and non-addictive behaviors; candidate genes; hypodopaminergia; polymorphisms; reward deficiency.

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Conflict of interest statement

Dr Kenneth Blum reports personal fees from VNI, ELECTRONICWAVEFORM LABS, during the conduct of the study; grants from NIH, outside the submitted work; in addition, Dr Kenneth Blum is the inventor of the Genetic Addiction Risk Severity (GARS) test and KB220 pro-dopamine variants and through his companies Synaptamine, Inc. and SpliceGen Holdings own all relevant worldwide patents. Dr Kenneth Blum has a patent 10,894,024 with royalties paid to SYNAPATAMINE. The authors report no other conflicts of interest in this work.

References

1. Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263:2055–2060. doi:10.1001/jama.1990.03440150063027 - DOI - PubMed
1. Comings DE, Comings BG, Muhleman D, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA. 1991;266:1793–1800. doi:10.1001/jama.1991.03470130073032 - DOI - PubMed
1. Ishiguro H, Arinami T, Saito T, et al. Association study between the −141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism. Alcohol Clin Exp Res. 1998;22:845–848. - PubMed
1. Arinami T, Itokawa M, Komiyama T, et al. Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese. Biol Psychiatry. 1993;33:108–114. doi:10.1016/0006-3223(93)90309-2 - DOI - PubMed
1. Noble EP, Blum K, Khalsa ME, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 1993;33:271–285. doi:10.1016/0376-8716(93)90113-5 - DOI - PubMed

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[1] Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263:2055–2060. doi:10.1001/jama.1990.03440150063027 - DOI - PubMed

[2] Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263:2055–2060. doi:10.1001/jama.1990.03440150063027 - DOI - PubMed

[3] Comings DE, Comings BG, Muhleman D, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA. 1991;266:1793–1800. doi:10.1001/jama.1991.03470130073032 - DOI - PubMed

[4] Comings DE, Comings BG, Muhleman D, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA. 1991;266:1793–1800. doi:10.1001/jama.1991.03470130073032 - DOI - PubMed

[5] Ishiguro H, Arinami T, Saito T, et al. Association study between the −141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism. Alcohol Clin Exp Res. 1998;22:845–848. - PubMed

[6] Ishiguro H, Arinami T, Saito T, et al. Association study between the −141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism. Alcohol Clin Exp Res. 1998;22:845–848. - PubMed

[7] Arinami T, Itokawa M, Komiyama T, et al. Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese. Biol Psychiatry. 1993;33:108–114. doi:10.1016/0006-3223(93)90309-2 - DOI - PubMed

[8] Arinami T, Itokawa M, Komiyama T, et al. Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese. Biol Psychiatry. 1993;33:108–114. doi:10.1016/0006-3223(93)90309-2 - DOI - PubMed

[9] Noble EP, Blum K, Khalsa ME, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 1993;33:271–285. doi:10.1016/0376-8716(93)90113-5 - DOI - PubMed

[10] Noble EP, Blum K, Khalsa ME, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 1993;33:271–285. doi:10.1016/0376-8716(93)90113-5 - DOI - PubMed

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"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS)

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"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS)

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