Assessing the genetic risk for alcohol use disorders

Abstract

The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence. Research in humans and in animal models of human disease has provided important new information. Among the most commonly applied approaches used in human studies are family studies, case-control studies, and genome-wide association studies. Animal models have been aimed at identifying genetic regions or individual genes involved in different aspects of alcoholism, using such approaches as quantitative trait locus analysis, genome sequencing, knockout animals, and other sophisticated molecular genetic techniques. All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed. Newer studies, however, also are attempting to look at the genetic basis of alcoholism at the level of the entire genome, moving beyond the study of individual genes toward analyses of gene interactions and gene networks in the development of this devastating disease.

Figure

Strategies to identify genes contributing to alcohol dependence. A) Family study. In this figure, the squares represent males; the circles, females. The individuals with lines connecting their symbols produced children together and the lines down from that pair of individuals depict their offspring. Fully shaded symbols indicate individuals in the family who are alcohol dependent. The bars beside each symbol represent a region in the genome. Each individual has two copies of this region (one inherited from their mother and one from their father). The black bar carries a version of the gene (i.e., an allele) with a variation in its sequence that increases the risk of alcoholism. Notice that in this family, all four alcoholic individuals carry one copy of the allele that increases the alcoholism risk. The individuals who are not alcohol dependent do not carry this allele. If this pattern is repeated across many families, then there is likely to be a gene that influences the risk for alcoholism in this part of the genome. B) Case–control study. The three colors represent the three possible genetic makeups (i.e., genotypes) at the marker. The cases have more individuals with the green genotype and fewer with the blue genotype, whereas the controls have more individuals with the blue genotype and fewer with the green, suggesting that the green genotype is associated with an increased risk for alcohol dependence.