The genetics of alcoholism and other addictive disorders

Abstract

Addictions are common, complex disorders that are to some extent tied together by shared genetic and environmental etiological factors. They are frequently chronic, with a relapsing/remitting course. Addictive disorders, which are in part volitional, in part inborn, and in part determined by environmental experiences, pose the full range of medical, genetic, policy, and moral challenges. Genetic factors account for 40-70% of the variance in addiction liability. There is little evidence for large influences on overall population vulnerability from any single gene. Instead, multiple genetic loci are likely to be involved, each with a small attributable risk. Gene discovery is being facilitated by a variety of powerful approaches and tools, but is in its infancy. Susceptibility loci for addictions include both drug-specific genes (e.g., alcohol-metabolizing genes) and loci moderating neuronal pathways, such as reward, behavioral control, and stress resiliency, that are involved in several psychiatric diseases (e.g., MAOA and COMT). In recent years, major progress has been made in identification of genes using intermediate phenotypes such as task-related brain activation that confer the opportunity of exploring the neuronal mechanisms through which genetic variation is translated into behavior. Fundamental to the detection of gene effects are also the understanding of the interplay between genes and of genes/environment interactions. The identification of genes altering the liability to addiction and treatment response (e.g., OPRM1) could provide new therapeutic targets and an ability to individualize treatment. Although the genetic bases of addiction remain largely unknown, there are reasons to think that more genes will be discovered in the future. Multiple and complementary approaches will be required to piece together the mosaic of causation.