Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases

Introduction

Alcohol dependence is one of the major challenges to the worldwide healthcare system. Approximately 6% of all deaths are attributed to alcohol misuse and associated diseases (“Statistics & information,” 2015). At the same time, more than 5% of all cases of all burdens of disease and injury are caused by alcohol (“Statistics & information,” 2015). Alcohol affects individuals on a genetic level, ingraining itself into DNA, thus resulting in increased susceptibility to alcoholism in future generations of people.

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Although genetic predisposition towards the disease has been widely recorded and documented for more than several centuries, the significance of genetic influence in proportion to environmental, societal, socio-economic, and cultural factors remains unclear. Alcoholism is a multifactorial disease, with every case being different from another in which a singular factor or a combination of factors serves as the primary antagonist. The loci directly responsible for a genetic predisposition to alcoholism have not yet been discovered. This makes the analysis of the significance of their impact even more difficult. The purpose of this paper is to synthesize the existing data on genetic predisposition to alcohol and alcohol-related diseases by examining the latest available academic evidence.

What is Alcoholism?

Most medical researchers define alcoholism as a condition where an individual drinks large amounts of alcohol (over 20, 30 grams per day, depending on gender), has difficulty stopping, and suffers from withdrawal when alcohol runs out. There are many negative side effects of alcoholism, some of which include health hazards, social disabilities, and involvement in risky situations, like fights, spontaneous spending, unsafe sex, and others. Alcohol tolerance is developed over time, forcing the individual to consume more and more just to get the same effect. Alcohol is associated with numerous mental illnesses, heart diseases, liver cirrhosis, alcoholic fatty liver disease, Wernicke–Korsakoff syndrome, and many others. The disease is typically divided into two subgroups: alcohol abuse and alcohol dependence. However, as the two are typically correlated, they are collectively referred to as alcohol use disorder (AUD).

Genetics of Alcohol Dependence and Related Diseases: Study Findings

The majority of contemporary genetic studies of alcohol dependence focus on several objectives. The goals of the research include discovering genes that are responsible for an increased predisposition towards AUD, genes that protect an individual from developing such, genes responsible for a predisposition towards alcohol-based diseases, such as cirrhosis, and the connection between them. The article was written by Stickel, Moreno, Hampe, and Morgan (2017) examines the genetics of alcohol dependence and alcohol-related liver disease (ALD).

The researchers base their findings on the statistical analysis of the results of previous researchers, to determine the connection between certain genes and a genetic predisposition towards the disease. According to Stickel et al. (2017), “there is strong evidence of the genetic contribution of alcohol dependence. Some of the potential gene candidates include rs1229984 in ADH1B in Europeans, East Asians and African Americans and rs671 in ALDH2 in East Asians” (p. 199). As for ALD, the researchers have concluded that there are many factors involved in the pathogenesis of the disease. It is not completely understood how environmental, behavioral, and genetic factors interact on a cellular and molecular level. However, Stickel et al. (2017) state that genes involved in the predisposition towards ALD (PNPLA3, TM6SF2, and MBOAT7) are not related to genes responsible for the development of alcoholic dependence itself.

These findings are largely mirrored by another study published a year earlier, by Tawa, Hall, and Lohoff (2016), who have provided an overview of available evidence to determine genes responsible for alcohol predisposition. Their results are based on twin studies, linkage studies, and candidate gene association studies, and genome-wide association studies (GWAS), which have provided the most results. According to GWAS analysis, there are connections in alcohol predisposition/resistance based on the ethnicity of the individual. According to Tala et al. (2016), candidate genes are as follow:

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  • C12ORF24 (rs2074356) for Korean men;
  • KEGG pathway ID 72- Synthesis and degradation of ketone bodies for European and African-American individuals;
  • GABRA2 and PBX/knotted 1 homeobox 2, PKNOX2 for European and African-American individuals;
  • Ankyrin repeat domain 7, ANKRD 7, and Cytokine-like 1, CYTL1, (rs6466686-rs4295599-rs12531086) (halotype) for Caucasians;
  • 51 gene loci, including CDH11, CDH13 for European-Americans;
  • ALDH2 (rs671) for individuals of east-Asian descent (Korean, Chinese, Japanese);
  • ADH1C (rs1614972) for individuals of German descent;
  • TPARP, CYFIP2, THEMIS, PSG11 – for Europeans, European-Americans, and Australians;
  • Near semaphorin 3E, SEMA3E – for Australian and Dutch.

As it is possible to see, potential candidates in this study are numerous, which makes defining the exact impact of every genome and loci particularly difficult and labor-intensive.

Verhulst, Neale, and Kendler (2015) performed the last research reviewed in the scope of this paper. They studied the heritability of alcohol use disorders by performing a meta-analysis of twin and adoption studies. Their results do not concern themselves with the type of genes involved in a predisposition towards alcohol, but rather the overall strength of influence of genetic factors on the outcome. According to the study, heritability factors play a dominant role in over 50% of all cases. Environmental factors play a significant role only in 10% of the entirety of cases examined. However, the strength of environmental proportions differed greatly across all studies. Nevertheless, the researchers stand by their results and claim that “multiple genetically informative studies of this syndrome have produced consistent results that support the validity of this heritability estimate” (Verhulst et al., 2015, p. 1061).

Synthesis and Conclusions

Since alcoholism is a complex and multifactorial disorder, all studies involved have a high level of heterogeneity when compared one to another. Due to the potential dangers of substance overuse, randomized control trials are impossible, and researchers have to rely on large-scale observational studies, twin studies, and adopted studies. Data collection instruments for those are interviews and self-reported evidence, which can be erroneous when evaluating the environmental factors affecting individuals.

Although Verhulst et al. (2016) state that roughly 50% of all cases of alcoholism are hereditary and that the environment plays a lesser and less coherent part in determining predisposition towards it, these results differ from statements made in other studies, which claim that defining the exact proportions of influence for genetic and environmental factors is currently impossible. Numerous genes may be attributed to the development of alcoholism, but the sheer multitude of them makes definitive predictions impossible. Nevertheless, all findings concur that genetic predisposition plays a large role in the development of alcoholism.

It is possible to develop preventive measures based on these conclusions. Parental history should be assessed voluntarily, to determine if a child has the potential for developing alcoholism in the future. Parents should be warned about this potential danger so that they could use this knowledge in parenting and education. In addition, genetic predisposition could be counted on when treating individuals suffering from alcohol addiction. If alcoholism has been present in his or her family line, it should affect the intensity of treatment and care, as these individuals are more likely to resist the treatment and suffer from a relapse. Nevertheless, the subject of genetics in alcohol dependence deserves additional research to provide accurate results.

References

Statistics & information on alcoholism & addiction treatment help. (2015). Web.

Stickel, F., Moreno, C., Hampe, J., & Morgan, M. Y. (2017). The genetics of alcohol dependence and alcohol-related liver disease. Journal of Hepatology, 66(1), 195–211.

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Tawa, E. A., Hall, S. D., & Lohoff, F. W. (2016). Overview of the genetics of alcohol use disorder. Alcohol and Alcoholism, 51(5), 507-514.

Verhulst, B., Neale, M. C., & Kendler, K. S. (2015). The heritability of alcohol use disorders: A meta-analysis of twin and adoption studies. Psychological Medicine, 45(5), 1061–1072.

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StudyCorgi. (2021, June 23). Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases. Retrieved from https://studycorgi.com/genetic-predisposition-to-alcohol-dependence-and-alcohol-related-diseases/

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"Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases." StudyCorgi, 23 June 2021, studycorgi.com/genetic-predisposition-to-alcohol-dependence-and-alcohol-related-diseases/.

1. StudyCorgi. "Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases." June 23, 2021. https://studycorgi.com/genetic-predisposition-to-alcohol-dependence-and-alcohol-related-diseases/.


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StudyCorgi. "Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases." June 23, 2021. https://studycorgi.com/genetic-predisposition-to-alcohol-dependence-and-alcohol-related-diseases/.

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StudyCorgi. 2021. "Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases." June 23, 2021. https://studycorgi.com/genetic-predisposition-to-alcohol-dependence-and-alcohol-related-diseases/.

References

StudyCorgi. (2021) 'Genetic Predisposition to Alcohol Dependence and Alcohol-Related Diseases'. 23 June.

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