title: Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans.
abstract: This review provides a broad overview of the state of research in the genetics of anxiety disorders (AD). Genetic epidemiological studies report a moderate level of familial aggregation (odds ratio: 4-6) and heritability estimates are about 30-50%. Twin studies suggest that the genetic architecture of AD is not isomorphic with their classifications, sharing risk factors with each other. So far, linkage and association studies of AD have produced inconclusive results. Genome-wide association studies of AD can provide an unbiased survey of common genetic variations across the entire genome. Given the shared causes of AD that transcend our current diagnostic classifications, clustering anxiety phenotypes into broader groups may be a powerful approach to identifying susceptibility locus for AD. Using such a shared genetic risk factor, meta-analyses of genome-wide association studies of AD conducted by large consortia are needed. Environmental factors also make a substantial contribution to the cause of AD. Although candidate gene studies of gene by environmental (G × E) interaction have appeared recently, no genome-wide search for G × E interactions have been performed. Epigenetic modification of DNA appears to have important effects on gene expression mediating environmental influences on disease risk. Given that G × E can be linked to an epigenetic modification, a combination analysis of genome-wide G × E interaction and methylation could be an alternative method to find risk variants for AD. This genetic research will enable us to utilize more effective strategies for the prevention and treatment of AD in the near future.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Shimada-Sugimoto
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otowa
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Hettema
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics*; D057890:Epigenomics; D059647:Gene-Environment Interaction; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans
keywords: anxiety disorders; epidemiology; epigenetic; gene environmental interaction; genetic