Genetics and genomics of alcohol sensitivity Molecular Genetics and Genomics

Your genetics can influence how likely you are to develop AUD, but there’s currently no evidence of a specific gene that directly causes AUD once you start drinking. Many factors are involved in the development of AUD, but having a relative, or relatives, living with AUD may account for almost one-half of your individual risk. The accumulation of acetaldehyde manifests as symptoms such as facial flushing, rapid heartbeat, nausea, and dizziness. These symptoms are commonly seen in individuals of East Asian descent, who have a higher prevalence of the ALDH2 gene variant.

Is There an Alcohol Addiction Gene?

Sanchez-Roige and Palmer noted that their group has developed a 10-year partnership with 23andMe that has focused on numerous traits, especially those with relevance for addiction. This article does not contain any studies with human or animal subjects performed by any of the authors. Note that the official names of several ADH genes have been changed, and theliterature has been confused by some groups using non-standard names for some ofthe genes29. Your socioeconomic status is made up of economic and societal factors such as your income, level of education, employment, location of residence, and available resources. Having a close family relative, such as a parent, can account for up to 60% of your risk of developing AUD. According to the DSM-5-TR, the more relatives you have living with AUD and the closer they are to you in relation, the higher your individual genetic risk becomes.

Ancestrally diverse data collection

With increasing number of AFR GWAS now published, mainly from MVP, we were able to estimate genetic correlations between AUD and a limited set of traits in AFR. As in EUR, AUD in AFR was genetically correlated with substance use traits including OUD, smoking trajectory (that identifies groups of individuals that follow a similar progression of smoking behavior), and maximum habitual alcohol intake. PheWAS of PRS in AFR from PsycheMERGE and Yale–Penn confirmed that AUD is genetically correlated with substance use traits. Further, the genetic relationship between mental health phenotypes (i.e., PTSD, anxiety, and depression) and phenotypes indexing problematic alcohol use/symptoms of AUD versus non-pathological use differs.

• Acute effects are characterized by agitation and sedation, whereas long-term effects result in induction of tolerance and addiction.
• Some of the text from this section is overlapping with our prior published gSEM manuscript26.
• Individuals with the ALDH2 gene variation have a reduced ability to break down acetaldehyde, leading to an accumulation of this compound in the body.
• Studies on rat brain homogenates suggest that ethanol metabolism proceeds here via catalase and cytochrome P450 (CYP2E1), which inactivate about 60–70 % and about 20 % of ethanol, respectively, via oxidation (Zimatkin et al. 2006).
• Many datasets, including the one used in the study, rely heavily on individuals with European ancestry.
• GWAS of AUD have recently achieved the necessary sample sizes required to identify genome-wide significant risk loci and demonstrated that the disorder is genetically complex with many loci of small effect contributing to its etiology.

Risk Factors: Varied Vulnerability to Alcohol-Related Harm

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 to you if you have a family history of AUD. While genetics can play a significant role in your overall AUD risk assessment, it isn’t the only factor that can elevate your chances of developing AUD.

• To date, individual GWASstudies on alcohol dependence and related phenotypes have been relatively modestin size, and most do not reach genome-wide significance.
• It is estimated that up to 50% of people of East Asian descent have this genetic mutation, while the prevalence is much lower in other populations.
• The presence of the ALDH2 gene variant not only affects a person’s alcohol tolerance but also has implications for their overall health.
• In addition to the ADH gene, variations in genes related to the production and metabolism of certain neurotransmitters, such as dopamine and serotonin, may also influence an individual’s alcohol tolerance.
• This metabolic switch channels excess metabolic energy into the synthesis of fatty acids and contributes to the development of fatty liver syndrome during excessive alcohol consumption.

Convergent evidence linking association to brain

This individualized approach can empower individuals to make informed decisions about their alcohol consumption and identify their risk factors for developing alcohol-related problems. With the knowledge gained from genetic counseling, individuals can work towards developing personalized treatment plans and interventions to address their specific needs and reduce the potential negative consequences of alcohol consumption. Understanding the role of dopamine receptors in alcohol tolerance has important implications for the treatment and prevention of alcohol use disorders. By identifying individuals with specific genetic variations, healthcare professionals can develop personalized interventions to help individuals reduce their alcohol consumption and prevent the development of alcohol-related problems. Alcohol tolerance, which refers to the body’s ability to adapt to the effects of alcohol, is also influenced by genetic factors.

Table 1. Criteria for alcohol use disorders.

It highlights the interplay between genetics and alcohol tolerance, and provides insights into the mechanisms underlying alcohol-related reactions in the body. Further research is needed to fully understand the genetic mechanisms underlying alcohol flush reaction and its impact on alcohol tolerance. However, it is clear that genetics plays a significant role in determining an individual’s response to alcohol. In summary, there are numerous coding and noncoding variations in the ADH genes, at least some of which can affect risk for alcoholism. Additional studies of the full range of variations in these genes will provide a better understanding of the specific effects of individual variations and their impact on the risk for alcoholism. The values of liability-scale h2 of AUD of 12.4% (in LA) to 16.2% (in AFR) can be explained by the current study.

• Including participants from diverse ethnic backgrounds will provide a more comprehensive understanding of the genetic architecture of alcohol tolerance.
• In conclusion, alcohol tolerance is influenced by a combination of genetic and environmental factors.
• Additional studies of the full range of variations in these genes will provide a better understanding of the specific effects of individual variations and their impact on the risk for alcoholism.
• On the other hand, individuals with high levels of ADH and ALDH activity may be able to metabolize alcohol more efficiently and have a higher tolerance to its effects.
• That doesn’t mean you’ll absolutely develop AUD if you have a family member living with the condition.

The D1 receptor binds with excitatory G protein and activates adenylate cyclase (AC) via Gs; AC catalyzes the production of cAMP and cAMP regulates cAMP-dependent protein kinases to open calcium ion channels. D2 receptors bind with inhibitory G protein and thus reduce the production of AC and resulting cAMP. K.E.B. conducted analyses, wrote Method and Results, and generated the original idea for analyses, S.E.C. wrote Introduction, S.E.H. wrote Discussion, A.G. Although the plan had been to include all items described above, upon viewing the loadings of the three factor model, the AUDIT-T from 23andMe had a near zero loading (−0.01, NS) on the AUD factor. Since the AUDIT-T is comprised of items capturing alcohol use (AUDIT-C) and alcohol problems (AUDIT-P), we opted to omit this item from the model entirely, rather than allowing it to load at a near zero level on one of those two factors and potentially water down the factor it loads on. Thus, the steps that are described in the next section pertain to the models we are calling “final”, in which all items described earlier—with the exception of AUDIT-T from 23andMe—were included.

Consequently, acetaldehyde accumulates in the body, leading to symptoms such as facial flushing, headaches, nausea, and rapid heartbeat. Young adult twins and their non-twin siblings were participants in how to build alcohol tolerance the Nineteen and Up study24. Most alcohol-dependent cases were mild, with 70% of those meeting AD criteria reporting only three or four dependence symptoms and ≤5% reporting seven dependence symptoms. In this study, we use the same definitions, defining AUD by meta-analyzing AUD and AD across all datasets, and defining PAU by meta-analyzing AUD, AD and AUDIT–P (Table 1). Independent genetic signals from the cross-ancestry meta-analysis were searched in OpenTargets.org37 for druggability and medication target status based on their nearest genes. Among them, OPRM1 implicated naltrexone and GABRA4 may implicate acamprosate, both current treatments for AUD.

Whole exome sequencing analysis identifies genes for alcohol consumption

Genetics can play a role in determining a person’s alcohol tolerance, but it is not the sole factor. While certain genetic variations may predispose someone to have a higher alcohol tolerance, other factors such as drinking habits, overall health, and environmental influences also contribute to a person’s alcohol tolerance. It is important to note that alcohol tolerance is not solely determined by genetics and can vary among individuals. Additionally, expanding research efforts to diverse populations will be crucial in further elucidating the genetic factors underlying alcohol tolerance. Many studies to date have primarily focused on individuals of European descent, limiting the generalizability of findings.