A brief history of research on the genetics of alcohol and other drug use disorders.

ObjectiveThis article reviews developments in research on genetic influences on alcohol and other drug use and disorders over the past 7 decades.MethodThe author began with a review of the flow and content of articles published in the three iterations of the journal since 1940 and then used a PubMed search of genetics of alcohol and other drug-related topics to gain a broad overview of developments in this field.ResultsThe literature demonstrates the rapid metamorphosis of genetic research from the ideas of Mendel to an understanding that the substance use disorders are complex, genetically influenced conditions where genes explain up to 60% of the picture. Most genes operate through additional intermediate characteristics, such as impulsivity and a low sensitivity to alcohol, some of which are substance specific and others related to substances in general. Using linkage, association, genome-wide association, and other modern methods, investigators have identified a diverse range of genetic variations that affect substance-related phenomena.ConclusionsGenetic studies regarding alcohol and other drug use and problems have grown dramatically in the past 75 years. We currently have a much more sophisticated understanding of these influences, and the rapid development of new methods has the promise of continuing what has been a solid contribution of important findings in recent years

A Long-Term Study of Sons of Alcoholics.

Men with a family history of alcoholism appear to have a lower intensity reaction to alcohol's effects than those without this family history. This study investigated whether a lower reaction could encourage greater alcohol consumption among family history-positive (FHP) subjects, predisposing them to develop alcohol-related problems. A family history of alcoholism was associated with increased risk of alcohol dependence and abuse among study subjects. Likewise, over half of the FHP's whose reactions to alcohol were low had developed alcoholism at a 10-year followup

Alcohol, Anxiety, and Depressive Disorders.

Alcoholics frequently experience episodes of intense depression and/or severe anxiety. Depressed or anxious alcohol-dependent people often believe that they drink to relieve symptoms of sadness or nervousness. However, research does not unanimously support the prior existence of severe depressive or anxiety disorders as a usual cause of alcoholism. A review of recent literature (from family studies, prospective investigations, and studies of children of alcoholics) on the complex interaction between alcohol dependence and independent anxiety/depressive disorders reveals that if an association between alcoholism and anxiety/depressive disorders does exist, it likely operates in a relatively small subgroup of alcoholics at the same time. Psychological symptoms may carry a worse prognosis for alcohol-related problems, and these symptoms must be addressed early in alcoholism treatment

Co-occurring risk factors for alcohol dependence and habitual smoking.

Smoking and alcohol dependence frequently occur together, and both behaviors are determined in part by genetic influences. The Collaborative Study on the Genetics of Alcoholism (COGA), which is investigating the genetic factors contributing to alcohol dependence, also allows for analyses of the genetic factors determining smoking. Using a sample comprised of alcoholics and their closest (i.e., first-degree) relatives as well as a community-based control sample, COGA investigators found that both alcohol dependence and habitual smoking were transmitted within families. This familial transmission resulted from both common and drug-specific influences, which likely include genetic factors. Further genetic studies (i.e., candidate gene studies and genomic screening approaches) have identified several DNA regions that may contain genes that confer a susceptibility for alcoholism. Some of those genes also may contribute to the risk for habitual smoking