title: Genetic studies of alcohol dependence in the context of the addiction cycle.
abstract: Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50-60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled "Alcoholism".
authors.affiliation: National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), Division of Neuroscience and Behavior, 5635 Fishers Lane, Bethesda, MD 20852, USA. Electronic address: reillymt@mail.nih.gov.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Reilly
authors.affiliation: National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), Division of Neuroscience and Behavior, 5635 Fishers Lane, Bethesda, MD 20852, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Noronha
authors.affiliation: National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), Chief, Laboratory of Neurogenetics, 5635 Fishers Lane, Bethesda, MD 20852, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.affiliation: National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), Director NIAAA, 5635 Fishers Lane, Bethesda, MD 20852, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D016739:Behavior, Addictive / Q000235:genetics*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide
keywords: Addiction cycle; Alcohol dependence; Alcohol use disorder; Genetic mapping; Genetics; Genome-wide association study