Genes Contributing to the Development of Alcoholism: An Overview Alcohol Research: Current Reviews
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. While the D2 dopamine receptor gene did not have the effect expected on alcoholism, the study contributed to moving forward genetic research. “We know now that it was only a first step of a very long road of complex genetics,” said Renato Polimanti, a colleague of Gelernter at the Yale School of Medicine. In contrast to Angier’s conclusion that AUD is decided by the environment, scientists have since found multiple genetic players.
- A particularly attractive feature of studying rare variation in COGA is its family design, which aids the identification of both private and disorder‐generalized mutations.
- Mood and anxiety disorders fall into this category as well, and the association between CHRM2 variations, alcoholism and depression illustrates how these problems may stem in part from a common source.
- One way around this has been the use of intermediate phenotypes, including electrophysiological and imaging, that reflect mediating factors in behavior and are likely to be influenced by variation at fewer genes.
Genome-wide Association Studies
COGA is a family based, diverse (~25% self‐identified African American, ~52% female) sample, including data on 17,878 individuals, ages 7–97 years, in 2246 families of which a proportion are densely affected for AUD. All participants responded to questionnaires (e.g., personality) and the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA) which gathers information on psychiatric diagnoses, conditions and related behaviors (e.g., parental monitoring). how old is demi lavato 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.
Some of these candidate genes encode components of various brain chemical systems that allow communication among nerve cells. Two of these genes are the dopamine D2 receptor gene (DRD2) and a serotonin transporter gene (HTT). However, the analyses found no evidence that DRD2 affected the risk for alcoholism (Edenberg et al. 1998a) or that HTT was linked to either alcoholism in general or to a more severe form of alcoholism (Edenberg et al. 1998b). 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. And these distinctions will be important for identifying the genetics of addiction, the researchers said. Over the past few years numerous whole genome linkage studies have been performed in which the inheritance of phenotypes and genetic markers is followed in families 12,40.
Combining Results From Different Studies
Evidence from twin studies for shared genetic influences between alcoholism and internalizing disorders are more controversial 18,22,23. 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. This article has focused on questions about the relative importance of genetic and environmental influences on alcoholism. However, such questions are only a starting point for behavioral genetic research on alcoholism. Understanding more about how genes and environment act, co-act, and interact to determine differences in alcoholism risk remains a key goal of ongoing twin and adoption studies.
The Initial Study
Interestingly, these variations in GABRA2 do not change the protein structure of the GABAA receptor; instead they seem to modify production of the affected protein subunit, perhaps reducing the total number of functioning receptors. Complex epigenetic mechanisms that regulate gene activity without altering DNA code have been shown to produce long-lasting changes in gene expression essential to development and cellular differentiation and to adaptation to environmental changes. These mechanisms, that include DNA methylation, post-translational covalent modifications of histones, nucleosome sliding and nucleosome and histone substitution, cause modifications of chromatin conformation which, in turn, regulate gene expression (for review see Tsankova et al. 123). For example, the amount of DNA methylation in promoter regions correlates with gene inactivation.
An accompanying blog provides an overview of new findings with an eye towards public communication. Other enzymes that break down alcohol have also been studied for their genetic contribution to alcohol dependence. Alcohol dehydrogenase (ADH), the enzyme responsible for the first step in the conversion of alcohol to acetaldehyde, for example, is actually produced by a family of genes, each of which affects different properties of the enzyme. Our own studies of a U.S. population of European descent have recently provided strong evidence that variants in the ADH4 genes in particular enhance the risk of alcoholism in members of that population, although exactly how these ADH4 variants affect alcohol metabolism remains to be discovered.
While the adult data in COGA are extensive, two family cohorts, adolescent and young adults in Prospective Study and older participants in Lifespan Study, will benefit from additional participants and data collection. The COGA initiative is focused on optimizing the use of the past COGA data and completing data collection across the lifespan. They also underscore the need to understand how subtle differences in physiology can contribute to a disorder as complex as addiction. Decades ago researchers began investigating the widely observed tendency of persons from Chinese, Japanese or other East Asian backgrounds to become « flushed » when they drank an alcoholic beverage.
Clinicians are in the earliest stages of using genetic variants to shape treatment decisions for alcoholism, and in the future we expect to have molecular guidelines to help develop such individualized strategies. The two earliest Iowa adoption studies (i.e., the LSS and CFS) show significantly elevated risk to adopted-away sons from alcoholic biological backgrounds compared with control adoptees (i.e., risk ratios of 3.5 and 3.6, respectively), consistent with a genetic influence on alcoholism risk in men. For male adoptees in the remaining two samples, the risk to those from an alcoholic background is not significantly higher than that for control adoptees. In these latter studies, however, the rates of alcoholism are high, even in the control adoptees (from 55 to 58 percent), raising the possibility that the entire sample of adoptees, on average, came from high-risk biological backgrounds. Postulating a 28-percent prevalence rate for alcohol problems in the general population, the risk of alcoholism in adopted-away sons from alcoholic backgrounds is significantly greater than that for the general population. The data from the second part of the split sample—the replication sample, which comprised 1,295 people from 157 families—generally supported the initial findings (Foroud et al. 2000).