Genetics and Addictions

Genetics research includes not only examination of the patterns of inheritance in families but also direct examination of the genes themselves. Advances in molecular biology have allowed researchers to literally break open a chromosome and examine the coding that determines our genetic traits. The ability to alter the gene structure of experimental animals has led to testing of the function and importance of specific genes, sometimes with unexpected results.

A primary aim is to determine who is vulnerable to addiction and why. An ongoing study by Dr. Mark Schuckit at the University of California at San Diego is tracking several traits in three generations of men initially selected for study in the mid-1970s. Findings so far confirm the “low response” factor seen in the sons of alcoholics. Those sons were later recontacted and found to be three times more likely to develop alcoholism than those in the general population. Beginning in 1999 a third generation was added to the study. As these children grow up, several variables will be measured to see if it is possible to predict the risk of alcoholism and target specific traits for prevention and early intervention. This valuable cohort group of almost fifteen hundred subjects also provides a potential source of data for more detailed genetic analysis.

Family studies on the genetics of drug dependence are also under way. Dr. Kathleen Merikangas and her colleagues at Yale University recently published an analysis of the families of almost three hundred individuals with drug dependence.

Their findings confirmed that the presence of addiction to a particular substance elevates risk for addiction to that substance in family members. Studies such as these provide a focus for more detailed inquiry into the genetics of specific drug addictions.

The amount of research on drug addiction has lagged behind research on alcoholism because of differences in funding patterns and political interest. Sharp increases in the prevalence and cost of drug dependence documented by epidemiological surveys have led, though, to increased support for research on the various aspects of illicit drug addiction.

The DNA molecule is composed of interlocking strands of molecules set up like a twisting ladder. The rungs of the ladder are composed of pairs of four different molecules in different combinations. Each individual has a unique sequence of these four molecules, since no two individuals share identical genetic characteristics unless they are identical twins.

However, there are stretches of DNA which code specific characteristics (hair or eye color, for example) that will be the same for different groups of individuals. DNA molecules are found in the chromosomes, which are x-shaped structures found in the nucleus of the cell. Each chromosome contains details concerning the structure and function of a particular part of the body. The first step in understanding genetics was to discover what genes - or groups of DNA molecules - are contained in which chromosome. We are now able to untwist the DNA molecules that form the genes and figure out what combinations of the ladder’s rungs correspond to a particular genetic trait.

There are several basic approaches to the study of the genetics of a particular condition. The first of these is linkage analysis. In this type of study the genes of affected individuals are compared to the genes of family members with and without related disorders to see if patterns cluster in certain areas of the chromosome. Very simply put, the DNA is unwound and compared so as to determine whether there are specific repeating patterns that can be identified in people with the disease in question. In allele-sharing studies the genes of people from the same family with the same condition are compared. Again, patterns that recur are identified as possible sites that control the expression of the disease in question.

Association studies compare the genes of those who have the disorder to the genes of those who don’t. A particular pattern of genes that consistently shows up in people with the disorder, but not in those without it, is considered to be associated with the disorder. Proceeding further in the lab to identify what characteristic that gene controls helps us to understand what causes the disorder. Often in this type of study something as subtle as a slight difference in the structure of a single enzyme is found.

In the fourth type of study strains of experimental animals with specifically bred traits are compared. One type of experimental animal is called a “knock-out” animal. Its genes are altered in the lab so that a specific gene at a specific location is removed. This is generally the gene that controls a characteristic that has already been identified and is suspected of being involved in the disorder being studied. As a result of this genetic manipulation the animal does not express the traits controlled by that gene. When these animals are exposed to a particular drug or some other experimental condition, their response can be compared to the response of animals who have an intact set of genes. This gives the researcher more detailed information on what that gene does by observing what happens when it is absent.

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