Alcohol use disorder does not have a clear pattern of inheritance, although many affected individuals have a family history of problems with alcohol or other substances. Children of people with alcohol use disorder are two to six times more likely than the general public to develop alcohol problems. This increased risk is likely due in part to shared genetic factors, but it may also be related to environment, lifestyle, and other nongenetic influences that are shared by members of a family. Compared to other genetic predictors, the genomic pattern identified here was also a more sensitive predictor of having two or more substance use disorders at once. The genomic pattern linked to general addiction risk also predicted higher risk of mental and physical illness, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease, and chronic pain conditions. In children aged 9 or 10 years without any experience of substance use, these genes correlated with parental substance use and externalizing behavior.
Supplementary information
- Alcohol use disorder (AUD) is a condition where it’s difficult to stop drinking alcohol, even when it affects your work, relationships, and health.
- According to scientists, drunken drosophila fruit flies behave the same way humans do when they are drunk.
- It includes alcoholism, also called alcohol addiction, which is a long-lasting (chronic) condition characterized by a powerful, compulsive urge to drink alcohol and the inability to stop drinking after starting.
- However, sex-stratified GWAS also identified two female-specific signals for AUDIT-C (Supplementary Data 3, Supplementary Figs. 9, 10) and one for AUD (Supplementary Data 4, Supplementary Figs. 11, 12).
- According to a review from 2016, genes that promote alcohol metabolism and the production of enzymes, such as alcohol dehydrogenase and aldehyde dehydrogenase, can be protective against AUD.
It includes alcoholism, also called alcohol addiction, which is a long-lasting (chronic) condition characterized by a powerful, compulsive urge to drink alcohol and the inability to stop drinking after starting. In addition to alcoholism, alcohol use disorder includes alcohol abuse, which involves problem drinking without addiction what it is, causes, symptoms, types and treatment addiction. The most significant pathway is reactome ethanol oxidation for both traits in both EAs and AAs. Multiple GO biological processes are enriched for AUDIT-C (Supplementary Data 13, Supplementary Fig. 17) and AUD (Supplementary Data 14, Supplementary Fig. 18), including ethanol and alcohol metabolism.
What are the risk factors for AUD?
2 By convention, gene names in animals are written in uppercase and lowercase and italicized. Gene names in humans are written in all caps and are italicized, whereas the acronyms for the encoded proteins are all caps but not italicized. By Buddy TBuddy T is a writer and founding member of the Online Al-Anon Outreach Committee with decades of experience writing about alcoholism. Because he is a member of a support group that stresses the importance of anonymity at the public level, he does not use his photograph or his real name on this website.
Whole genome sequencing
For studies of rare variants, families are quite valuable for sortingout true positives from the background of individual variations that we allharbor. Twin studies and other research have shown that genetics accounts for about half of the overall risk for alcoholism. In the context of AUD, GCTA could be applied to the subsets of previously discussed SNPs that reached genome-wide significance and were correlated with alcohol-dependent phenotypes. GCTA estimates could be used for diagnostic purposes and provide further insight as to whether variants in ADH and ALDH, among other genes, in fact contribute to the genetic predisposition for AUD. Genetic testing is already providing opportunities for self-assessment that were impossible in the past, and the demand for genetic profiling will increase in the coming years. Microarrays, often called gene chips, can be used to detect a person’s gene variants as well as variations in gene activity and to produce a series of medical, psychiatric and behavioral recommendations that the individual may take or leave as he or she wishes.
Genetics of alcohol-associated diseases
Researchers at Yale School of Medicine and the University of Pennsylvania searched for genetic variants among individuals with a history of heavy drinking and those identified as having alcohol use disorder. The study included 274,000 subjects enrolled in the United States Veterans Administration’s Million Veteran Program. Twin and adoption studies have shown that half of the risk of alcohol dependence, a subtype of AUD, is heritable9.
In many cases, the initial linkage studies were followed by moredetailed genetic analyses employing single nucleotide polymorphisms (SNPs) that weregenotyped at high density across the linked regions. Some of the genes identifiedthrough this approach have been replicated across a number of studies and appear tobe robust genetic findings. Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. Researchers have used both case–control and family studies to identify genes related to alcoholism risk. In addition, different strategies such as candidate gene analyses and genome-wide association studies have been used.
In 2021, more than 46 million people in the United States aged 12 or older had at least one substance use disorder, and only 6.3% had received treatment. Moreover, people who use drugs are facing an increasingly dangerous drug supply, now often tainted with fentanyl. Approximately 107,000 people died of drug overdoses in 2021, and 37% of these deaths involved simultaneous exposure to both opioids and stimulant drugs. Drug use and addiction represent a public health crisis, characterized by high social, emotional, and financial costs to families, communities, and society. It is now appreciated that a whole spectrum of allele frequencies andeffect sizes may play roles, from common variations with small effects throughrare variants of large effect. As whole exome and whole genome sequencingtechnologies come down in cost, they are being applied to identifying rarevariants.
If you have multiple relatives with alcohol addictions or other substance use disorders, you may have inherited the genes that put you at risk. The more family members (related by birth) you have with an alcohol problem, the higher your risk. AUD is a complex disorder, and likely hundreds if not thousands of genes contribute to its broad and varied phenotype. an in-depth look at kratoms long-term side effects & how to avoid them In addition, given the current chip-based methodology of GWAS, this technology by design misses rare de novo mutations or insertion/deletion variants (Stefansson et al., 2008; Walsh et al., 2008; Clarke and Cooper, 2010). Furthermore, several findings have been for intronic SNPs with no clear understanding of their underlying biological relevance.
As the field of psychiatry transitions to the DSM-5 criteria for AUD, there may also be changes in the functional variants identified by GWAS. Future GWAS should focus on the endophenotypes of AUD in order to better understand the genetic connections to specific behavioral symptoms. Likewise, it will be important to separate the role of genetic variants due other substance use disorders and to comorbid psychiatric disorders.
Most robust associations that have been reported in common disease haveemployed tens of thousands of samples and are now beginning to combine severalstudies of these magnitude into even larger meta analyses. The alcohol researchcommunity has begun to form larger consortia for meta-analyses and it is anticipatedthat with the resulting increase in sample size the number of robust associationswill increase. A second approach that will likely benefit the alcohol researchcommunity will be greater examination of pathways or gene sets. These approacheshave been quite fruitful for some studies and need to be employed in analyses ofalcohol-related traits and phenotypes. Over the next few years, we anticipate theidentification of additional common and rare variants contributing to the risk ofalcohol dependence. Vrieze et al. (2013) found that, in biometric twin models, behavioral inhibition was highly genetically correlated with all substance use traits (nicotine use/dependence, alcohol consumption, alcohol dependence, and drug use).
Several study designs—including case–control studies, population studies, and family studies—have been used to test whether a specific gene or gene variant affects risk for a disease (for more information, see the article by Foroud and Phillips, pp. 266–272). For example, it is much easier to collect individual dangers of detoxing from alcohol at home cases (i.e., people with alcoholism) and control subjects (i.e., nonalcoholic people) or samples of the general population than it is to recruit family samples. On the other hand, family studies avoid the problem of incomplete ethnic/population matching1 that can confound case–control studies.
While the recent use of GWAS to identify the underlying genetic components of AUD has been promising, there are several limitations of GWAS that must be considered. GWAS use a ‘hypothesis-free’ design by genotyping hundreds of thousands to 2 million markers simultaneously in cases and controls. This approach generates large amounts of data and creates issues with regard to multiple testing. As a result, early GWAS in psychiatric phenotypes yielded negative findings (Sklar et al., 2008; Craddock and Sklar, 2013).
Individuals with isoforms of ADH that oxidize ethanol at a faster rate and/or isoforms of ALDH that oxidize acetaldehyde at a slower rate are protected against AUD due to the unpleasant effects that result from acetaldehyde accumulation. Alcohol Use Disorder (AUD) is a chronic psychiatric condition characterized by drinking patterns that lead to detrimental emotional, physical, and social outcomes. The Centers for Disease Control and Prevention (CDC) has reported that alcohol use contributes to approximately 88,000 deaths annually in the United States (Stahre et al., 2014), reflecting high morbidity and mortality. To diagnose individuals with AUD, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (Mizokawa et al., 2013) utilizes 11 criteria pertaining to excessive alcohol use, alcohol abuse, and alcohol dependence.