Treatment approaches increasingly consider genetic profiles to tailor interventions, aiming to improve outcomes in individuals affected by alcoholism. Overall, the study of genetics in relation to alcoholism continues to be a promising field, with implications for prevention, diagnosis, and treatment strategies. These data continue to serve, not only as a platform for characterization of loci discovered in our own GWAS of behavioral and brain data but also for emerging signals from larger scale meta‐analytic GWAS of AUD. The GWAS study (cohort 1) on which our discovery was based contained males as probands but contained males and females as controls. It is possible that some of the nominally significant SNPs identified in the discovery GWAS have to do with gender differences rather than to alcoholism per se, or at least may have to do with male alcoholism.

Holistic Approaches to Address Genetic Risk

Your genetic risk refers to the likelihood that specific genes or genetic variants passed down to you will lead to a particular condition. From its inception, COGA has focused on the importance of brain function and on developing novel brain intermediary phenotypes of risk for and consequences of alcohol use and AUD. This has been done through the examination of neuropsychological tests and noninvasively recorded brain electrical activity during resting state and cognitive tasks, and more recently, by deriving measures of neural synchrony and connectivity (3. Brain Function).

Gene-Gene Effects within Biological Pathways

In addition, because heavy drinking can exacerbate age‐related physical and neurocognitive problems, interact with medications, and cause falls and accidents, especially in older adults, a longitudinal follow‐up of COGA participants aged 50 and older is in progress. Of note, assessments, interviewer training and data cleaning are standardized across all sites, with some variations in assessment driven by individual institutional IRB criteria. Taken together, these waves of longitudinal follow‐up provide a perspective of AUD risk and resilience across the lifespan. The goal of this series of reviews is to describe the study design, highlight the multi‐modal data available in the Collaborative Study on the Genetics of Alcoholism (COGA), and document the insights that these data have produced in our understanding of the lifecourse of AUD. COGA is an interdisciplinary project with the overarching goal of understanding the contributions and interactions of genetic, neurobiological and environmental factors towards risk and resilience over the developmental course of AUD, including relapse and recovery.

Does having a genetic predisposition to alcoholism mean that a person will definitely become an alcoholic?

• Initial recruitment prioritized families with at least three first degree relatives meeting criteria for alcohol dependence (i.e., densely affected) although many families include more than three individuals with AUD, hence the higher than population prevalence of alcohol dependence and AUD (Table 1).
• Individuals with a genetic predisposition should be educated about the increased risk they face and the potential consequences of excessive alcohol consumption.
• While there is overlap between alcohol use disorder and alcohol consumption, the researchers did further analysis and found a “distinct genetic architecture” differentiating alcohol abuse from alcohol consumption.
• It is no secret that the genes we inherit from our parents determine simple physical traits such as hair color and height.
• If you are struggling with chronic alcohol misuse or addiction, inpatient and outpatient addiction treatment programs are available to provide you with the support and education needed to overcome your addiction.
• Twin studies reveal consistently the existence of shared genetic influences between alcoholism and externalizing disorders 17-20.

A non-exhaustive list of convergent findings across studies includes a region on chromosome 4q, that contains the alcohol dehydrogenase (ADH) gene cluster 96,97,99,100, and a chromosome 4p region near the centromere containing a γ-aminobutyric acid receptor (GABAA) gene cluster 96,99. In the COGA sample there was also evidence for linkage to chromosomes Halfway house 1 and 7, and to chromosome 2 at the location of an opioid receptor gene 96. A region on chromosome 1 was linked to alcoholism and affective disorder in the COGA data set 102, supporting further the existence of a genetic overlap between alcoholism and internalizing disorders. Alcohol use disorder is a complex disease that is influenced by both genetic and environmental factors. Recent advancements in genomic medicine have allowed researchers to better understand the genetic predisposition to alcoholism and develop targeted treatment strategies.

What is genetic predisposition to alcoholism?

• Thedifficulties of genetic studies are compounded by environmental heterogeneity inaccess to alcohol and social norms related to drinking.
• A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD.
• Several epidemiology studies have been conducted to attempt to categorize genes and characteristics related to alcohol dependence.
• The sharing of data and biospecimens has been a cornerstone of the COGA project, and COGA is a key contributor to large-scale GWAS consortia.
• The latter point suggests that, similar to bipolar disorder53 and schizophrenia,54 the contextual cumulative combinatorics of common gene variants and environment55 has a major role in risk for illness.
• Scientists have learned through studies of identical and non-identical twins that alcohol use disorder is heritable, with genetic factors accounting for about half of the risk of alcohol dependence.

By understanding the risks, individuals can make conscious choices to either abstain from alcohol altogether or consume it in moderation. In conclusion, genomic medicine has provided valuable insights into the genetic basis of alcohol use disorders. Identifying genetic markers and understanding their impact on an individual’s susceptibility to alcoholism can inform personalized treatment approaches. By integrating genomic information into clinical practice, healthcare providers can optimize treatment outcomes and improve the lives of individuals affected by alcoholism. Genetic testing can be particularly valuable for individuals with a family history of alcoholism. If a person has close relatives who have struggled with alcohol addiction, genetic testing can help identify their own risk and guide them towards making informed decisions about alcohol consumption.

In the study of complex disorders, it has become apparent that quitelarge sample sizes are critical if robust association results are to beidentified which replicate across studies. Meta-analyses, whichcombine results across a number of studies in order to attain the criticalsample sizes needed, are being developed. Early behavioral symptoms of alcoholism include frequent intoxication, a pattern of heavy drinking, drinking alone or in secret, or drinking alcohol in high-risk situations (such as drinking and driving). Erratic or dramatic changes in behavior with alcohol consumption, “blacking out,” or not remembering events that occurred while drinking, may also be signs of the disorder. The physical symptoms of alcoholism are many and can include jaundice (yellowing of skin or eyes), hepatitis (enlarged liver), abdominal pain, nausea and vomiting, infections, malaise (not feeling well), weight loss, fluid retention, problems with memory, and anorexia (decreased eating).

Genetics Of Alcoholism

However, longitudinal studies have shown that anxiety disorders such as panic disorder and social phobia predict subsequent alcohol problems in adolescents and young adults 24. The strongest and most consistent findings for GWAS for AUD are for alcohol metabolizing genes, as in a recent study in an East Asian (Korean) sample of alcoholics in which ALDH2 and ADH1B showed up as GWAS signals with genome-wide significance 68. Subsequent analysis showed that AUTS2 was implicated in alcohol consumption in mice and alcohol sensitivity in drosophila 69. COGA is one of the few family‐based genetic projects with a significant number of African Americans, who are greatly underrepresented in such studies, particularly those with family‐based designs. COGA’s asset is its family‐based longitudinal design that supports an intensive clinical, behavioral, genetic, genomic and brain function data collection.

• In addition to rapid tolerance, flies develop chronic tolerance after prolonged exposure to a low concentration of ethanol 43.
• In that regard, chronic exposure to ethanol modifies DNA and histone methylation, histone acetylation, and microRNA expression.
• By continuing to unravel the complexities of this disease, we can improve prevention efforts and develop more effective treatments.
• The fact that our genetic testing worked for both alcohol dependence and alcohol abuse suggests that these two diagnostic categories are actually overlapping, supporting the DSM-V reclassification of a single category of alcohol use disorders.
• He led blockbuster films such as Crimson Tide with Denzel Washington and Enemy of the State with Will Smith.

Symptom expression of alcohol dependence may differ by culture and ethnicity, because people of different cultures may express physical and mental ailments differently. Ethnic and racial groups may respond differently to alcohol and medications used to treat alcohol dependence. Some groups may even enjoy greater protection against alcoholism as a result of their genetics. For instance, vulnerability to cardiomyopathy and Wernicke-Korsakoff’s syndrome may be heritable and may vary by ethnicity. Latino men, for example, tend to show greater susceptibility to alcohol-related liver damage than do White men.

Genetic Influences on the Development of Alcoholism

Another line of inquiry is the interaction between alcohol consumption and epigenetics, the way in which genes are expressed or suppressed. According to the National Institute on Alcohol Abuse and Alcoholism’s 2013 report on epigenetics, researchers have found that alcohol use may impair or disrupt gene expression in the liver, gastrointestinal tract, and brain. Studies also suggest that it may play a part in the development of cancers of the liver, breast, respiratory tract, and digestive tract as well as in fetal alcohol syndrome. Until we get there, research will continue focusing on identifying genetic variants and possible mechanisms behind risk. Polimanti explained that for certain illnesses like cardiovascular disease, the field of genetics is expected to transform treatments in the coming years. “We will keep doing gene discovery and use increasingly advanced technology to deliver this information and get a deeper understanding of the role genetics play in human health,” Zhou said.

In contrast to Angier’s conclusion that AUD is decided by the environment, scientists have since found multiple genetic players. A review of studies from 2020, which looked at a genome-wide analysis of more than 435,000 people, found 29 different genetic variants that increased the risk of problematic drinking. Throughout this manuscript, we use the terminology of “alcohol use disorder” to discuss individuals meeting diagnostic criteria for case status, but we note that this has been variously defined in the COGA sample depending on the diagnostic system at the time of sample recruitment.

In addition, 9871 individuals have brain function data from electroencephalogram (EEG) recordings while 12,009 individuals have been genotyped on genome‐wide association study (GWAS) arrays. A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD. This overview provides the framework for the development of COGA as a scientific resource in the past three decades, with individual reviews providing in‐depth descriptions of data on and discoveries from behavioral and clinical, brain function, genetic and functional genomics data. The value of COGA also resides in its data sharing policies, its efforts to communicate scientific findings to the broader community via a project website and its potential to nurture early career investigators and to generate independent research that has broadened the impact of gene‐brain‐behavior research into AUD. Despite using lines of evidence for our CFG approach that have to do only with alcoholism, the list of genes identified has a notable overlap at a pathway analysis level (Table 2B and Supplementary Table S2B) and at a gene level (Figures 4 and 5) with other psychiatric disorders. Moreover, we tested in alcoholics genetic risk predictive panels for bipolar disorder53 and for schizophrenia54 generated in previous studies by us, and show that they are significantly different in alcoholics versus controls (Figure 6), beyond the overlap in genes with alcohol.