In other words, there will be no single “gene for alcoholism” but rather variations in many different genes that together, interacting with the environment, place some people at significantly higher risk for the disease. This genetic and environmental variability (i.e., heterogeneity) makes the task of identifying individual genes difficult. However, the COGA project was designed with these difficulties in mind and incorporated strategies to meet the challenges. This article briefly reviews these strategies and summarizes some of the results already obtained in the ongoing COGA study. 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).
Impact on your health
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. The Collaborative Study on the Genetics of Alcoholism (COGA) is a large-scale family study designed to identify genes that affect the risk for alcoholism (i.e., alcohol dependence) and alcohol-related characteristics and behaviors (i.e., phenotypes1). Data collection, analysis, and/or storage for this study take place at nine sites across the United States. Because alcoholism is a complex genetic disorder, the COGA researchers expected that multiple genes would contribute to the risk.
What gene is responsible for increased AUD risk?
Genes may interact with specific toxic environments, such as abuse or neglect, to result in problems for some gene carriers but not for others. Nobody gets to be alcohol-dependent without making some poor choices, but clearly some people are more sensitive to alcohol than others in the same set of circumstances, and scientists are working to identify the sources of that vulnerability. Our research group recently discovered, for example, that variation in a gene encoding a receptor involved in taste perception, known as hTAS2R16, is significantly linked to alcoholism in the COGA subjects. The risk variant, which causes decreased sensitivity to many bitter taste compounds, is uncommon in European Americans, whereas 45 percent of African-Americans carry this version, making it a much more significant risk factor in that population.
People
It is likely that, as for most complex diseases, alcohol dependence and AUDsare due to variations in hundreds of genes, interacting with different socialenvironments. An additional challenge in the search for genetic variants that affectthe risk for AUDs is that there is extensive clinical is alcoholism a genetic disease heterogeneity among thosemeeting criteria. Because the diagnosis of an AUD requires the presence of a set ofsymptoms from a checklist, there are many different ways one could meet thecriteria. There are 35 different ways one could pick 3 criteria from 7 (DSM-IValcohol dependence) and 330 ways to pick 4 from 11 (DSM-5 severe AUD). Thedifficulties of genetic studies are compounded by environmental heterogeneity inaccess to alcohol and social norms related to drinking. Neurons that bear GABA receptors are especially abundant in the brain’s frontal cortex, where a generalized loss of inhibition can cause seizures, and seizure disorders are commonly treated with medications that boost GABA activity, promoting inhibition.
Core Resource information on genetic vulnerability to AUD
This use of scientific knowledge is surely inevitable, especially in free nations with capitalist economies, where it will be market-driven and competitive. The scientific and academic communities must therefore help guide this process by distinguishing true physiological relations from false claims and by encouraging socially responsible uses for these discoveries. But the ability to tap into “big data” such as 23andMe’s research cohort as well as the UK Biobank, which Palmer and his team used for this study, has opened up new research opportunities for those studying behavioral traits — like addiction and substance abuse — as well as neuropsychiatric conditions and personality. 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.
- Such studies will enhance our understanding of the genetic and cellular interplay between AUD and AD, helping to guide interventions aimed at slowing cognitive decline in Alzheimer’s patients.
- The tendency to become dependent on alcohol has long been known to run in families, which for some only added to the social stigma attached to this complicated condition.
- The ISO 9001 standard is an internationally recognised standard that is based on a number of quality management principles including a strong customer focus, the management of process change, effective methods of reducing non- compliance, and the continual improvement in the quality of our services.
- 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).
Alcohol consumption negatively affects male fertility, particularly through its impact on spermatogenesis. Acute alcohol intake may disrupt sperm production by elevating oxidative stress and impairing Sertoli cell function, although human studies show inconsistent results. Chronic alcohol use is more clearly linked to reduced semen quality, including lower sperm volume, concentration, and morphology. Alcohol abuse, especially binge drinking, often leads to feminization symptoms due to hyperestrogenism and oxidative stress-induced damage to Leydig cells.
Genetics and alcoholism
The strategies for genetic analyses in the COGA study also had to accommodate the anticipated genetic complexity of alcoholism and the multiple phenotypes that would be collected. For participants from families with three or more alcoholic family members, the investigators conducted genetic analyses using microsatellite markers—DNA regions located across all chromosomes, in which short repeated sequences exist in many variants (i.e., alleles). More than 1.2 million genotypes have been generated on 2,310 people from families of alcoholics and 1,238 people from control families. By monitoring the inheritance patterns of such marker alleles within families with alcoholic members, the investigators could identify chromosomal regions that influence (i.e., show genetic linkage with) certain alcohol-related traits.