Genetics of alcoholism

Alcohol Health & Research World, Wntr, 1991 by James R. Wilson, Lawson Crowe

The excessive use of alcohol by a significant number of individuals in our society is a major cause of an contribution to human suffering, death, disease, crime, and domestic disorder (U.S. Department of Health and Human Services 1990). Although the scale of misery has grown with the expansion of the population, alcohol abuse has been a continuing social problem from earliest times.

Historically, different societies have viewed the problem of excessive drinking in different ways. In Colonial America, drunkenness was seen as a sign of moral weakness (Rorabaugh 1979). The first serious suggestion that excessive drinking was itself a diseases appeared near the beginning of the 19th century (Rush 1785; Marconi 1959). The prevailing view of alcohol use advanced by the 19th and early 20th century Temperance Movement in the United States, Great Britain, and continental Europe, however, was that alcohol was itself a "poison" harmful to various body parts and that this harm could be transmitted to the offspring of the drinker. From this perspective, all persons who ingested alcohol were at risk for the destruction of their health and for transmitting the deleterious effects of drinking to their children (Beauchamp 1980; Crowe 1985).

The idea that drinkers were at risk for transmitting acquired disabilities to their offspring was discredited early in the 20th century (Elderton and Pearson 1910). Primarily for social and political reasons--emerging individualism as well as the advance of science--the concept of alcoholism as a disease and the view that only some drinkers were at risk emerged fully after the repeal of Prohibition (Moore and Gerstein 1981). The view of alcohol as a poison was abandoned in favor of the idea that a significant distinction could be made between "normal" and "abnormal" drinkers. Abnormal drinkers were thought to be susceptible or predisposed to becoming alcoholic. That some people seem able to drink more than others without apparent ill effect is a commonplace and ancient observation (for example, see Hamilton and Cairns 1982).

Thus, the stage was set to search for an underlying biological or psychological cause of excessive drinking (Jellinek 1960; Lender 1979; Pattison et al, 1977). In recent years, the disease concept of alcoholism has been reinforced by the hypothesis that at lease some persons are at risk because they inherit a genetic predisposition to alcohol abuse. Many scientists believe that a genetic predisposition to alcohol abuse helps to explain the wide variability in the human response to alcohol. In addition, many researchers and clinicians believe that the best hope for prevention and effective treatment lies in the identification of genetic determinants responsible for susceptibility to alcohol abuse, knowledge that could be applied, for example, to the development of screening tests for detecting those at risk long before the onset of alcohol use. If such tests were available for young people at risk, it is assumed that appropriate preventive measures could be developed. As we explain below, although continuing efforts to elucidate genetic and behavioral factors predisposing an individual to alcoholism may well lead to methods for early detection, such information will need to be interpreted and applied with caution.

IS THERE A GENETIC BASIS FOR

ALCOHOL ABUSE?

That some families show a disproportionate amount of alcohol abuse has been well documented (for review, see Goedde and Agarwal 1987 and Cotton 1979). Less obvious is whether this increased incidence should be attributed to genes or to shared environment or, perhaps more accurately, to how much of each. Vivid early writings about families consisting of drunks, prostitute, lazybones, imbeciles and ne'er-do-wells (Crowe 1985) failed to take into account the economic hardship and class prejudice, or both, in which many of these families were immersed. Although modern behavioral genetic designs make due allowance for both genetic and environmental influences and their potential interactions and correlations, it seldom is possible to examine all influences adequately in a single study.

The relatively simple, powerful methods of single-gene (Mendelian) analyses have repeatedly been used to study the occurrence of alcoholism in families. To date no single-gene pattern of inheritance has been found to fit the data. The situation is reminiscent of the state of affairs early in this century, when researchers in the emerging field of genetics complained that Mendel's rules were good only for trivial characteristics, such as the color of peas; and that the inheritance pattern of "important" traits, such as human abilities, did not fit simple Mendeliam ratios.

This controversy was resolved by postulating the existence of "polygenes." Polygenes, also known as quantitative trait loci, do not produce a dramatic all-or-none effect such as those that Mendel worked with: instead, two or more polygenes must be present and summate their effects before a phenotypic result (or physical or behavioral manifestation) can be observed, each adding its increment to the expression of color, or height, or IQ.