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

References

• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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 Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Volkow ND, Fowler JS, Wolf AP, et al. Effects of chronic cocaine abuse on postsynaptic dopamine receptors. Am J Psychiatry. 1990;147:719–724. doi:10.1176/ajp.147.6.719
   PubMed Web of Science ®Google Scholar
• Comings DE, Flanagan SD, Dietz G, Muhleman D, Knell E, Gysin R. The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem Med Metab Biol. 1993;50:176–185. doi:10.1006/bmmb.1993.1059
   PubMedGoogle Scholar
• Noble EP, St Jeor ST, Ritchie T, et al. D2 dopamine receptor gene and cigarette smoking: a reward gene? Med Hypotheses. 1994;42:257–260. doi:10.1016/0306-9877(94)90127-9
   PubMed Web of Science ®Google Scholar
• Thompson J, Thomas N, Singleton A, et al. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics. 1997;7:479–484. doi:10.1097/00008571-199712000-00006
   PubMedGoogle Scholar
• Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry. 1991;48:648–654. doi:10.1001/archpsyc.1991.01810310066012
   PubMed Web of Science ®Google Scholar
• Gordis E, Tabakoff B, Goldman D, Berg K. Finding the gene(s) for alcoholism. JAMA. 1990;263:2094–2095. doi:10.1001/jama.1990.03440150102034
   PubMed Web of Science ®Google Scholar
• Blum K, Noble EP. The sobering D2 story. Science. 1994;265(5177):1346–1347. PMID: 7802784. doi:10.1126/science.7802784
   PubMed Web of Science ®Google Scholar
• Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA. 1990;264:3156–3160. doi:10.1001/jama.1990.03450240058040
   PubMed Web of Science ®Google Scholar
• Holden C. Alcoholism research. A cautionary genetic tale: the sobering story of D2. Science. 1994;264:1696–1697. doi:10.1126/science.8209249
   PubMed Web of Science ®Google Scholar
• Horgan J. D2 or not D2. A barroom brawl over an “alcoholism gene”. Sci Am. 1992;266(29):32. doi:10.1038/scientificamerican0292-32
   Google Scholar
• Gelernter J, O’Malley S, Risch N, et al. No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism. JAMA. 1991;266:1801–1807. doi:10.1001/jama.1991.03470130081033
   PubMed Web of Science ®Google Scholar
• Chen TJ, Blum K, Mathews D, et al. Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of “super normal controls” in psychiatricgenetic research of complex behavioral disorders. Med Hypotheses. 2005;65:703–707. doi:10.1016/j.mehy.2005.04.037
   PubMed Web of Science ®Google Scholar
• Neville MJ, Johnstone EC, Walton RT. Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat. 2004;23:540–545. doi:10.1002/humu.20039
   PubMed Web of Science ®Google Scholar
• Yang BZ, Kranzler HR, Zhao H, Gruen JR, Luo X, Gelernter J. Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. Alcohol Clin Exp Res. 2008;32:2117–2127. doi:10.1111/j.1530-0277.2008.00800.x
   PubMed Web of Science ®Google Scholar
• Jung Y, Montel RA, Shen PH, Mash DC, Goldman D. Assessment of the association of D2 dopamine receptor gene and reported allele frequencies with alcohol use disorders: a systematic review and meta-analysis. JAMA Netw Open. 2019;2:e1914940. doi:10.1001/jamanetworkopen.2019.14940
   PubMed Web of Science ®Google Scholar
• Blum K, Baron D, Lott L, et al. In search of reward deficiency syndrome (RDS)-free controls: the “holy grail” in genetic addiction risk testing. Curr Psychopharmacol. 2020;9:7–21. doi:10.2174/2211556008666191111103152
   PubMedGoogle Scholar
• Blum K, Bowirrat A, Gondre Lewis MC, et al. Exploration of epigenetic state hyperdopaminergia (Surfeit) and genetic trait hypodopaminergia (Deficit) during adolescent brain development. Curr Psychopharmacol. 2021;10. doi:10.2174/2211556010666210215155509
   Google Scholar
• Blum K, Wood RC, Braverman ER, Chen TJ, Sheridan PJ. The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes’ theorem. Funct Neurol. 1995;10:37–44.
   PubMed Web of Science ®Google Scholar
• Blum K, Sheridan PJ, Wood RC, et al. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med. 1996;89:396–400. doi:10.1177/014107689608900711
   PubMed Web of Science ®Google Scholar
• Blum K, Han D, Gupta A, et al. 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. J Pers Med. 2022;12:1385. doi:10.3390/jpm12091385
   PubMed Web of Science ®Google Scholar
• Blum K, McLaughlin T, Bowirrat A, et al. Reward deficiency syndrome (RDS) surprisingly is evolutionary and found everywhere: is it “blowin’ in the wind”? J Pers Med. 2022;12:321. doi:10.3390/jpm12020321
   PubMed Web of Science ®Google Scholar
• Levey DF, Stein MB, Wendt FR, et al. Bi-ancestral depression GWAS in the million veteran program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nat Neurosci. 2021;24:954–963. doi:10.1038/s41593-021-00860-2
   PubMed Web of Science ®Google Scholar
• Kimbrel NA, Ashley-Koch AE, Qin XJ, et al. A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci. Mol Psychiatry. 2022;27:2264–2272. doi:10.1038/s41380-022-01472-3
   PubMed Web of Science ®Google Scholar
• Hatoum AS, Colbert SMC, Johnson EC, et al. Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nature Mental Health. 2023;1:210–223. doi:10.1038/s44220-023-00034-y
   PubMedGoogle Scholar
• Thanos PK, Volkow ND, Freimuth P, et al. Overexpression of dopamine D2 receptors reduces alcohol self-administration. J Neurochem. 2001;78:1094–1103. doi:10.1046/j.1471-4159.2001.00492.x
   PubMed Web of Science ®Google Scholar
• Thanos PK, Rivera SN, Weaver K, et al. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci. 2005;77:130–139. doi:10.1016/j.lfs.2004.10.061
   PubMed Web of Science ®Google Scholar
• Thanos PK, Michaelides M, Umegaki H, Volkow ND. D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse. 2008;62:481–486. doi:10.1002/syn.20523
   PubMed Web of Science ®Google Scholar