Smoking and the Genetic Contribution to Alcohol-Dependence

by National Institute of Health

Genes influence a person's risk of becoming a smoker as well as the risk of alcohol dependence. Because substantially higher rates of smoking are observed in alcoholics than in control groups, uncovering the mechanisms underlying this association may have important implications for both treatment and prevention. Data analyses from the 1981 Australian twin panel cohort confirm a positive genetic correlation between regular smoking and the risk of alcohol dependence that remains significant, even when sociodemographic and personality variables as well as histories of other psychopathologies are taken into account. Acute or chronic effects of smoking on subjective responses to alcohol may play a role in this association.

Genes are known to play a role in determining a person's risk for becoming a regular smoker as well as his or her risk of becoming dependent on alcohol. In determining the contributions of genetic and environmental factors to the development of alcohol and tobacco problems, researchers frequently use two important tools-twin and adoption studies. Investigations using twins yield important information about the relative contribution of genetic and environmental factors to the development of a disease, such as alcoholism. Identical (monozygotic) twins share 100 percent of their genes, whereas fraternal (dizygotic) twins share, on average, 50 percent of their genes. Adoption studies typically compare the outcomes of adoptees who have biological parents with alcohol problems who grow up in various adoptive environments with the outcomes of adoptees without such family backgrounds who are raised in similar environments.

As reviewed elsewhere and supported by more recent twin studies, twin and adoption studies provide remarkably consistent evidence for an important genetic contribution to alcohol-dependence risk, accounting for as much as 40 to 60 percent of the total variation in risk in people of European ancestry. Alcoholism (variously defined) in adoptees is predicted by alcoholism in the adoptees' biological parents rathe As reviewed elsewhere and supported by more recent twin studies, twin and adoption studies provide remarkably consistent evidence for an important genetic contribution to alcohol-dependence risk, accounting for as much as 40 to 60 percent of the total variation in risk in people of European ancestry. Alcoholism in adoptees is predicted by alcoholism in the adoptees' biological parents rathe

As discussed elsewhere in this issue, researchers have established that rates of smoking are substantially elevated in alcoholics and have observed this finding both in clinical and in general community samples. We understand relatively little, however, about how the strong association between smoking and problems with alcohol arises. Twin analyses suggest an important overlap or correlation in the genetic factors that contribute to the risk for nicotine and alcohol dependence as well as between measures of smoking and alcohol use and heavy drinking. However, reporting correlations-even genetic correlations- tells us little about why a genetic relationship apparently exists between smoking and alcohol dependence. A number of different possibilities need to be considered, including the following:

Shared risk factors. Personality, sociodemographic variables, and history of a psychiatric disorder dependence and risk of smoking.

Direct causal influence of smoking. Smoking per se increases the risk that a person will develop problems with alcohol or, less plausibly (because of the typically earlier onset of regular smoking than of alcohol dependence), alcohol dependence increases the risk that a person will become a regular smoker.

Shared genetic vulnerability. Such vulnerability may arise, for example, because of alcohol's effects on important molecules (nicotinic receptors) involved in brain cell (neuron) communication.

These different hypotheses may have different implications for attempts to prevent or treat alcohol problems. Data from the 1981 cohort of the Australian twin panel allow us to explore the issue of shared genetic risk factors between alcohol dependence and smoking.

Smoking and Alcohol Dependence in the Australian Twin Panel

The Australian twin panel is a volunteer national twin sample maintained by the Australian National Health and Medical Research Council. Between 1980 and 1982, a questionnaire survey of adult twins registered with the panel produced replies from both members of approximately 3,800 twin pairs. Researchers conducted a followup telephone diagnostic interview survey between 1992 and 1994. The baseline questionnaire included questions about the respondents' smoking histories. From the duration of smoking reported in these data, respondents who had smoked only once or twice apparently classified themselves as "never smokers." Therefore, a positive response on the smoking section of the survey indicated a history of regular smoking rather than a history of experimentation with cigarettes. By combining these data with information about lifetime prevalence of alcohol dependence according to the American Psychiatric Association's Diagnostic and Statistical Manual, as reported in the interview survey, the usual finding can be replicated, indicating a strong association between smoking and alcohol dependence.

Without adjusting for covariates (sociodemographic and personality variables or a history of psychopathology), women with histories of regular smoking were five to six times more likely to report histories of alcohol dependence in the 1992-1994 survey compared with women who reported not smoking. In addition, men with histories of regular smoking were approximately two times more likely to report alcohol dependence compared with men who reported not smoking. Thus, the association between smoking and alcohol dependence was significantly stronger in women (the odds ratio, a measure of the strength of the association between two binary variables, was 5.9) than in men.

The more alcohol- dependence symptoms they reported (whether current or former), the more likely people were to report a history of regular smoking. Among smokers, however, no significant relationship existed between the number of cigarettes typically consumed per day and the risk of alcohol dependence in either gender.

The genetic overlap between smoking and a history of alcohol dependence can be assessed many different ways. One approach is to use a simple statistical model, in which a respondent's alcohol-dependence history is predicted as it relates to gender, twin-pair zygosity type (monozygotic or dizygotic), co-twin's smoking history (current or former smoker vs. nonsmoker), and interactions between these variables.

If a significant genetic correlation exists between smoking and alcohol dependence, smoking in one twin should correlate more highly in monozyalcohol dependence experienced by the co-twin. The two-way interaction between whether twins are monozygotic or dizygotic (twin-pair zygosity) and whether one twin reports a history of smoking provides a direct statistical test for this genetic correlation.

Without adjusting for covariates, a significant two-way interaction is observed.1When covariates are included - for example, extraversion, neuroticism, tough-mindedness, and social nonconformity; frequency of church attendance and religious affiliation; educational level; and history of major depression and conduct disorder - the effect of the twoway interaction is reduced but remains significant.2 In other words, the influence of sociodemographic, personality, and psychiatric risk factors on both the risk of alcohol dependence and the risk of regular smoking is not sufficient to explain the observed genetic association between smoking and alcohol dependence.

About the Author

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