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Dr. Nora Volkow How Drug Addiction Hijacks the Brain

Drug addiction, including alcoholism, effects the brain in different ways. This looks at the pharmacology of addiction.

Alcohol dependence is partially (38-64%) attributed to heritability (1) . The other major contributing factor to alcohol dependency is environment (environmental factors can include family history, peer substance abuse, male gender, cultural background, psychiatric disorders, and alcohol consumption at a young age) (1) . Due to the complexity of environmental influence, the factor is not well defined. Environmental factors can have different effects in populations and factors that can increase risk for alcohol dependence can include chemistry of the brain, the livers efficiency to process alcohol, and impulse control (1).

Alcohol Dependence in MenEdit

Estimated risk of alcohol dependence in men is determined by 23 and Me based upon on a genome wide association study of approximately 500 males that were clinically diagnosed as being alcohol dependent. 121 single nucleotide polymorphisms (SNPs) were identified in the study that conferred elevated risk of alcohol dependence (2) .
AlocholSNPS

SNPs identified as significant with regard to alcohol dependence in men (2).

There were also 19 additional candidate genes selected from animal studies that exhibited differential expression in those animals that were found to consume more alcohol. In the subsequent follow-up analysis, two SNPs were found to be specific genome wide; rs7590720 and rs1344694, which are both located in the 2q35 chromosomal region (2). These findings are consistent with previous studies that have implicated the 2q35 chromosomal region with alcohol phenotypes. Nine additional SNPs were located in suspect genes such as a cadherin superfamily member; CDH13, and alcohol dehydrogenase gamma (ADH1C). This study is used by 23 and Me to predict alcohol dependence in men by examining the analyzing the rs7590720 loci. This is the only SNP they take into consideration when predicting alcoholism in men (see JMB results for more information).

AlcoholismEdit

  • Analysis of Previous Study Reporting with Regard to DRD Taq1A Allele and AlcoholismGo to (2).
  • Effect Size Estimate (log OR) Related to Year of PublicationGo to (3)
To determine risk of alcoholism, 23 and Me utilizes a study that examined the relationship between the dopamine D2 receptor (DRD2) Taq1A polymorphism and alcoholism (3). This investigation tied in multiple studies to increase the data set and also examined potential publication bias by analyzing the results when specific studies were included/excluded from the analysis. Overall the group found that the DRD2 Taq1A polymorphism does correlate with an increased risk of alcoholism (3). It is important to note, however, that the severity of this risk increase can be variable depending on the target population, and may not exist in certain populations at all.

Alcohol Withdrawal Seizure SusceptibilityEdit

The dopamine transporter (DAT1/SLC6A3), specifically the variable nucleotide tandem repeat region of allele A9, has been associated with alcohol withdrawal symptoms including seizures (4). Scientists had opposing views on the subject and the topic was of some debate. Strat et al. investigated SNPs in the 3' region of the DAT1 to determine the validity of previous claims. They found that there was an increased risk (~3.5, P =0.019) for alcohol withdrawal symptoms and seizures. Two SNPs; rs27072 and rs27048 were found to be correlated with risk to alcohol withdrawal seizures specifically. While this study reinforced the already present notion, more studies are needed to understand the relationships more comprehensively. 

Dr. JMB ResultsEdit

Alcohol Dependence in Asians: N/A - following family lineage evaluation

Alcohol Dependence in Men: A GG phenotype at rs7590720 leaves Dr. JMB at a moderately higher risk of developing alcohol dependence (2)

Alcoholism: The rs1800497 loci in Dr. JMB's genome is GG which leaves him with typical odds of alcoholism. Each adenine at this loci increases risk (3).

Withdrawal Seizure Susceptibility: If Dr. JMB was alcohol dependent his risk of seizures from withdrawal would be typical with a CC genotype at rs27072 (4).  

Genomic Lesson Learned: With regard to the results coming from this portion of the 23 and me analysis, Dr. JMB should be aware of alcohol consumption patterns to ensure a dependence is not developed. The rs7590720 locus leaves Dr. JMB at a slightly elevated risk to alcohol dependence compared to other men. While, some heritable factors can effect an ability for an individual to metabolize alcohol, this is not the case for JMB.

ReferencesEdit

1. https://www.23andme.com/you/journal/pre_alcohol_dependence/overview/

2. Treutlein J, Cichon S, Ridinger M, et al. Genome-wide Association Study of Alcohol Dependence. Arch Gen Psychiatry. 2009;66(7):773-784. doi:10.1001/archgenpsychiatry.2009.83.

3.M R Munafò, I J Matheson, and J Flint. (2007). Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case–control studies and evidence of publication bias. Molecular Psychiatry. doi:10.1038/sj.mp.4001938

4. Yann Le Strat, Nicolas Ramoz, Paul Pickering, Virginie Burger, Claudette Boni, Henri-Jean Aubin, Jean Adès, Philippe Batel, Philip Gorwood. The 3′ Part of the Dopamine Transporter Gene DAT1/SLC6A3 Is Associated With Withdrawal Seizures in Patients With Alcohol Dependence Article first published online: 7 DEC 2007. DOI: 10.1111/j.1530-0277.2007.00552.x

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