Sex differences in the genetic risk for alcoholism.

One of the characteristics influencing a person's risk for alcoholism is his or her sex, and various factors may contribute to sex differences in risk. Adoption studies have provided some evidence of possible sex differences in the heritability of alcoholism, but overall the findings have been inconclusive. Twin studies have consistently supported the role of genetic risk factors in the heritability of alcoholism in men, and shared environmental factors also play a role in the familiality of alcoholism among women. In addition, sex differences exist in the patterns of transmission of alcoholism between family members. However, the genetic epidemiology research conducted to date on this issue has several limitations, some of which may be resolved by future molecular genetic studies. KEY WORDS: gender differences; genetic linkage; hereditary factors; risk factors; twin study; adoption study; epidemiological indicators; etiology; molecular genetics; AOD (alcohol and other drug) use susceptibility; AOD dependence potential; comorbidity; alcoholic beverage One of the factors associated with a person's risk for alcoholism1 is his or her sex. In this article, the term "sex" is used in both its biological sense (i.e., as a variable based on genetic differences between males and females) and its cultural meaning (i.e., in the sense of gender roles). Sex is associated with both biological risk factors (e.g., sex-specific hormone systems) and cultural risk factors (e.g., social expectations about how men and women use alcohol). An understanding of the mechanisms influencing sex differences in risk can help illuminate not only the differences in men's and women's drinking behavior and related problems but also the biological and cultural bases for variability within each sex. Sex differences in the factors underlying the development of alcoholism (i.e., its etiology) may be manifested as differences in prevalence, in the magnitude of genetic influences, and in the sources of genetic influences (i.e., sexspecific transmission of genetic risk factors). Studies in many cultures have found that the prevalence of alcoholism and heavy drinking generally is higher among men than among women. Both cultural and biological explanations have been invoked to account for this difference, but the mechanisms remain unclear. Moreover, differences in prevalence may arise even if the mechanisms underlying alcoholism development do not differ between the sexes. In this case, the same genetic factors could predispose men and women to alcoholism, but other sex-specific genetic and/or environmental factors could influence whether alcoholism develops in a given person. The magnitude of genetic influences on alcoholism risk may also be sex specific. Evidence from twin and adoption studies of alcoholism in males has consistently supported the existence of moderate genetic influences, accounting for about half of the population variation in liability to develop alcoholism (Prescott 2001). However, as will be described in this article, the evidence regarding the role of genetic factors in alcoholism in women has varied across studies. Such sex differences in the magnitude of genetic influence could arise from the interactions between genes associated with alcoholism risk and other physiological processes. For example, numerous physiological differences between men and women in the rate of alcohol absorption and metabolism are likely to be genetic in origin and may influence the development of alcoholism. Another potential manifestation of sex differences in alcoholism risk is the presence of sex-specific etiological factors. In this case, the risk that a relative of an alcoholic will develop alcoholism is greater when the relative and the alcoholic are of the same sex than when they are of different sexes. Sex-specific differences in etiology could be caused by genes that exhibit different levels of activity in men and women or which are modified by other sex-specific genetic or environmental factors to make male and female relatives less similar. …