Recent advances in genetic studies of alcohol use disorders

Over the past decade there have been tremendous advances in large scale SNP genotyping technologies and next generation sequencing and these technologies, including GWAS arrays and whole genome sequencing, are now widely available. Results of GWAS suggest that numerous common variants with very small effect and potentially rare variants with large effects are likely to encode proteins within, or regulate, numerous biological pathways. The current hope is that with very large sample sizes, GWAS will provide novel information about genetic underpinnings of alcoholism, including gene pathways that are altered in disease. Genetic vulnerability to alcoholism may originate in personality traits (such as anxious, dysphoric temperament and impulsivity) that predispose to alcohol seeking behavior, differential response to the effects of alcohol or differential variation in the neurobiology underlying addiction and physiological response to stress. Although alcoholism is often comorbid with other psychiatric disorders the heritability is largely disease specific 1. The exception is nicotine addiction with which there is a strong genetic correlation 1.

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The genes with the clearest contribution to the risk for alcoholism andalcohol consumption are alcohol dehydrogenase 1B (ADH1B) andaldehyde dehydrogenase 2 (ALDH2; mitochondrial aldehydedehydrogenase), two genes central to the metabolism of Substance abuse alcohol (Figure 1)20. Alcohol is metabolized primarily in the liver, although thereis some metabolism in the upper GI tract and stomach. The first step in ethanolmetabolism is oxidation to acetaldehyde, catalyzed primarily by ADHs; there are 7closely related ADHs clustered on chromosome 4 (reviewed in20). The second step is metabolism of theacetaldehyde to acetate by ALDHs; again, there are many aldehyde dehydrogenases,among which ALDH2 has the largest impact on alcohol consumption20. Awareness of the need for large sample sizes for GWAS has resulted in the formation of large scale collaborations for sharing data, such as the Psychiatric Genomics Consortium 82.

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In addition to genes, environmental influences also play a role in the risk for AUD. There were three major goals in the establishment of the NIAAA/COGA Sharing Repository in 1996, over 36 years ago. First, there was the perceived need to have quality‐assured biosamples from each COGA participant and to minimize differences between individual COGA samples due to potential collection, extraction or storage variables. Impetus to establish an ongoing biorepository also came from the belief that developing technologies for genome analysis would improve in the future and likely become more cost efficient (e.g., single nucleotide polymorphism and DNA sequencing) and that ample amounts of biosample of consistent quality would be required for such analyses. Third, there was the desire to collaborate with other groups by sharing COGA samples, thereby introducing more uniformity into research on the genetics of alcohol use disorder.

What are the protective factors for AUD?

Other health experts told Fox News Digital that there are pros and cons to this type of genetic testing. All genetic tests should be approached with caution, as they can sometimes lead to more questions than answers, according to Lee. The ADH1B and ADH1C genes help break down ethanol (alcohol) into the chemical acetaldehyde, he said. Dr. Frances Lee — a hepatologist (liver doctor) who specializes in alcohol-related liver disease at Mount Sinai Health Systems in New York City — is not affiliated with any of the lab companies, but commented to Fox News Digital about these testing kits. The test looks for mutations in the ADH and ALDH genes, which affect metabolism, according to several laboratory company websites that produce the testing kits. These could be signs that you have an inherited intolerance to alcohol — and a mutated gene could be the culprit, according to Cleveland Clinic.

• Healthcare professionals use the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to diagnose AUD.
• Despite the significant genetic overlap between the AUDIT-C and AUD diagnosis, downstream analyses revealed biologically meaningful points of divergence.
• The AUDIT consists of ten multiple-choice questions to assess your behaviors regarding alcohol consumption.

Many approaches to creating polygenic scores, from linkage disequilibrium (LD) clumping or pruning and thresholding approaches, to modern Bayesian methods, and even functional polygenic signatures, are available. Some researchers have hypothesized that there may be large panels of rare functional variants, each of alcoholism and genetics large effect, that predict risk for alcoholism with different variants occurring in different people. It is becoming increasingly easy, and the costs are rapidly decreasing, to detect rare variants using next-generation sequencing.

According to scientists, drunken drosophila fruit flies behave the same way humans do when they are drunk. In addition, a fruit fly’s resistance to alcohol appears to be controlled by the same molecular mechanism as humans. While genetics can account for up to 60% of AUD risk, not everyone with a family history of AUD will develop the condition. AUD isn’t directly caused by genetics, but genetics may predispose you to developing AUD later in life. This risk is considered hereditary and may be passed down https://ecosoberhouse.com/ to you if you have a family history of AUD.

Enrichments for chemical and genetic perturbation gene sets and for the GWAS catalog for both traits are shown in Supplementary Data 15–18 and Supplementary Figs. Understanding the link between alcoholism and genetics is crucial for identifying risk factors and improving prevention strategies. While genetic factors play a significant role, environmental influences are equally important. Understanding the role of genetic predisposition can help individuals make informed decisions about their drinking habits.

Like many other complex traits, alcoholism appears to be clinically and etiologicaly hetrogenous13. This implies that there might be several steps and intermediate conditions in the development of AUD. Information about the underlying genetic factors that influence risk to AUD can be derived from multiple levels of AUD including amounts of drinks (Alcohol consumption), severity and symptoms of alcohol abuse and dependence. Commonly, genome wide association studies (GWAS) of alcoholism have focused on phenotypes based on the Diagnostic & Statistical Manual of Mental Disorders (DSM)14. In the 4th edition of the DSM (DSM-IV), alcohol dependence (AD) and abuse were considered as mutually exclusive diagnoses that together made up AUDs.