Alcohol addiction is a growing concern in both developed and developing nations, influenced by a complex interplay of genetic and environmental factors. It is often co-morbid with other psychiatric disorders that share common neurobiological reward mechanisms. The exploration of genetic causes in psychiatric disorders began with alcohol addiction, with early studies in the 18th century identifying variants in alcohol-metabolizing enzymes as risk moderators. Advances in genetic research, particularly Genome-Wide Association Studies (GWAS) in the 20th century, have expanded the focus to genes associated with GABA receptors. However, the overall progress in uncovering the genetic basis of alcohol addiction has been relatively slow compared to other psychiatric disorders. The high rate of co-morbidity and the absence of a single genotype point toward the pleiotropic nature of genes involved in alcohol addiction. The discovery of the ALDH22 allele in the 1980s, which significantly reduces the risk of alcohol dependence, underscores the protective genetic mechanisms influencing addiction vulnerability. This allele, prevalent among East Asian populations but rare in Europeans and Africans, has been linked to a markedly lower odds ratio for alcohol dependence (0.33), with no reported cases among individuals homozygous for ALDH22. Future research should prioritize understanding the pleiotropic molecular mechanisms underlying alcohol addiction to advance prevention and treatment strategies.
Alcohol is steadily increased in developed and developing nations. Both genetic and environmental factors interplay in the aetiology and relapse of alcohol addiction. Alcohol addiction has been always co-morbid with other psychiatric disorders that commonly share the reward mechanism. Addiction The first invention of genetic cause for psychiatric disorders goes to alcohol addiction. In 18th century, the variants of alcohol metabolizing enzymes have been identified and were believed to be moderating the risk of Alcohol addiction. However the advancing genetic methods has moved beyond the genes related to alcohol metabolizing enzymes to genes associated with GABA receptors, identified by Genome Wide Association Study in 20th century. But the overall progress has been very slow when compared to the genetic discovery in other psychiatric disorders. Since, Alcohol addiction is highly co-morbid with other psychiatric disorders as represented by the Dual diagnosis in Alcohol Addiction; a single genotype is lacking paving the way for pleiotropic character of the genes associated with Alcohol Addiction. Future research should focus on the pleiotropic molecular mechanisms of Alcohol Addiction.
Past twenty years have been a wandering experience in the wilderness and now getting a feelings of crossing the River Jordan in the discovery of Genetics of Alcohol Addiction. The Promised Land flowing with milk and Honey is far away in scientific Discovery of Alcohol Addiction. Substance abuse including Addiction to Alcohol is highly Co-Morbid. Alcohol Addiction has an underlying genetic link with many disorders sharing the reward mechanisms.37 percent of Alcohol Addiction has a Co-morbid Psychiatric disorders. The Aldehyde Dehydrogenase CALDH*2) variant was discovered in 1980s, found to be associated with decreased risk of Alcohol dependence. ALDH*2 results from Substitution of Lysine for Glutamate at position 504 resulting in nearly inactive ALDH2 enzymes metabolizing Alcohol. This allele is common in East Asian Population, but nonexistent in Europeans and Africans [1].
ALDH2 Allele has strong Protective effect on Alcoholism.The Odd ratio of Alcohol Dependence for Subjects with ALDH2*2 allele is 0.33 and No documented cases of Alcohol dependence who are homozygous for ALDH2*2 [2-3].
The Alcohol Dehydrogenase1B*2(ADH1B*2) allele in ADH1B gene that encodes the B2 Sub-unit of ADH and results in histidine instead of Arginine at position 48 [4]. ADH1B*2 is associated with more rapid alcohol oxidation to Acetaldehyde and is Protective against alcohol dependence with an odd ratio of 0.12 in a Chinese population. This variant common in Asian population and weak in Europeans.
The latest methods in genetic research involves Genome Wide Association Studies (GWAS).The first GWAS for alcohol dependence was published by Treutlen and Colleagues in 2009 [5]. Latest findings of ADH and ALDH genes associated with Alcohol Dependence were not significant.
Now, it is found that GABA receptor genes have been associated with alcohol dependence. This includes GABRG1, GABRA2, GABRA4 and GABRB1 [6]. Alcohol was the first behavioral disorder which validated the genetics contributed to psychiatry. But, only meagre portion of genetic variants have been explored in Alcohol Addiction [7].
Genetic research in Psychiatry has advanced but in Alcohol addiction it is in slow phase though Throughput technology has been put onto play at present. The combination of the heritability of substance dependence, the heritability of psychiatric illnesses and the co-morbidity of substance dependence with psychiatric illnesses indicates that specific genes may be pleiotropic. Future genetic studies should focus more on Addiction and related psychiatric co-morbidity.
Oota, H. et al. “The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination.” Annals of Human Genetics, vol. 68, no. 2, 2004, pp. 93–109.
Kendler, K.S. “The diagnostic validity of melancholic major depression in a population-based sample of female twins.” Archives of General Psychiatry, vol. 54, no. 4, 1997, pp. 299–304.
Thase, M.E. “Recognition and diagnosis of atypical depression.” The Journal of Clinical Psychiatry, vol. 68, 2007, pp. 11–16.
Edenberg, H.J. “The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants.” Alcohol Research & Health, vol. 30, no. 1, 2007, pp. 5–13.
Treutlein, J. et al. “Genome wide association studies of alcohol dependence.” Archives of General Psychiatry, vol. 66, no. 7, 2009, pp. 773–784.
Edenberg, H.J. et al. “Variations in GABRA2, encoding the α2 subunit of the GABAA receptor, are associated with alcohol dependence and with brain oscillations.” The American Journal of Human Genetics, vol. 74, no. 4, 2004, pp. 705–714.
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