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. The study is also important because of the massive health and socio-economic impacts of substance abuse in general. Even just looking at alcohol alone there is a vast health cost, with more than 3.3 million people worldwide die each year from excessive alcohol use, according to the World Health Organization. In the United States, the economic costs of alcohol abuse are estimated to be as high as $249 billion each year, according to the Centers for Disease Control.
The investigators chose a family study design to allow the use of multiple methods of genetic analysis. Systematic recruitment from outpatient and inpatient alcoholism treatment facilities and assessment of families initially was carried out at six sites across the United States, with a seventh site more recently. The study also included a large sample of control families that were randomly selected from the community.
What is the Genetic Heritability of Alcoholism?
One component of an ERP is a brain wave called P300, which typically occurs 300 milliseconds after a stimulus. Previous studies had found that a reduced amplitude of the P300 wave is a heritable phenotype that correlates with alcohol dependence and other psychiatric disorders (Porjesz et al. 1998). The genetic analyses of the COGA participants identified four regions, on chromosomes 2, 5, 6, and 13, that appear to contain genes affecting the amplitude of the P300 (Begleiter et al. 1998).
- The increasing availability of the DNA sequence of the entire human genome and knowledge of variations in that sequence among people are greatly aiding the current phase of the research.
- For individual studies, Heath and colleagues (in press) estimated the proportions of variability in alcoholism liability explained by genetic and family environmental influences.
- Over the next few years, we anticipate theidentification of additional common and rare variants contributing to the risk ofalcohol dependence.
Polygenic risk can also be challenging to communicate, and can lead to unrealistic expectations of what genomic medicine can do for the treatment and prevention of AUD. These were developed in collaboration with digital communication specialists and include short videos, text descriptions, interactive graphical elements, and key take‐aways, and can be found at cogastudy.org. An accompanying blog provides an overview of new findings with an eye towards public communication. The goal of genetic studies, however, is not only to find associations but also to understand how these variants might promote the development of AUD.
Undoubtedly, there is value in limiting the use of alcohol, nicotine and other mood-altering drugs in general. There is also value, however, in supporting individual self-knowledge as it pertains to susceptibility so that people can make informed choices for themselves and in shaping a culture that regards this as a positive goal. The genetic contributions to dependence identified so far affect many different aspects of human physiology, from alcohol metabolism to brain activity and taste perception just in the examples we have described.
A Pioneering Study
Meta-analysis is used to combine data from many different studies to improve the ability to detect small effects by improving the preciseness of estimates. Estimates of genetic and environmental effects did not appear to vary significantly within the group of U.S. studies or the group of Scandinavian studies. Family TiesAt coga’s outset, researchers at sites around the country sought to identify families severely affected by alcoholism. Previous twin, adoption and family studies had indicated that alcohol problems are strongly heritable–indeed, more than 50 percent of the overall risk for alcoholism is attributable to inherited factors, which makes family groups a powerful resource for tracking specific traits and linking them to the relevant genes. The effect of MAOA on the hippocampus, a brain region which is involved in the processing of emotional experience, may underlie the interaction between MAOA and childhood trauma.
Strategies for Identifying Genes Associated With Alcoholism Risk
This should allow the investigators to greatly narrow the regions and to identify individual genes in which variations affect the risk for alcoholism and the other phenotypes they are studying. The COGA investigators also evaluated electrophysiological variables, such as EEGs and ERPs, from study participants. EEGs measure overall brain activity, whereas ERPs are brain waves elicited in response to specific stimuli (e.g., a light or sound). Analysis of such electrophysiological data may reveal a subset of genes that affect these quantitative, biological phenotypes related to alcoholism (Porjesz et al. 1998, 2002).
Alcoholism is genetically complex, meaning that multiple genes are likely to be involved, and their interactions with one another and with an individual’s environment also have to be examined before a complete picture of the processes that can lead to the disorder is assembled. People are also complex and manifest problems with alcohol in diverse ways, especially in the early stages of disease, although cases come to resemble one another clinically in the later stages of illness. Thus, when investigating the biology of alcoholism, researchers must carefully define the problem–for example, distinguishing between true dependence on alcohol and alcohol abuse, which is a less medically severe syndrome. Other enzymes that break down alcohol have also been studied for their genetic contribution to alcohol dependence.
As the project enters its late third decade of scientific exploration, we approach our contributions to the study of AUD with optimism. Our science aims to identify pathways to enduring remission and processes that can be modified to minimize the deleterious impact of AUD across the lifespan. Through our collaborative gene‐brain‐behavior paradigm, we aspire to address both the causes and consequences of heavy alcohol use and AUD, which still contributes annually to 3 million preventable deaths Recovery National Institute on Drug Abuse NIDA globally.
