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.

Cross-generational influences on childhood anxiety disorders: pathways and mechanisms

“…This represents a moderate level of heritability and leaves most individual differences in vulnerability to anxiety to environmental influences. In a recently updated review the authors reached similar conclusions, but emphasized that genetic heritability seems to be to pathological anxiety overall, rather than to specific anxiety disorders (Shimada-Sugimoto et al 2015). Indeed, defining distinct phenotypes is one of the challenges faced by genetic research in general, and has been called the rate limiting factor in psychiatric genetic studies (Tsuang et al 1993).…”

“…In childhood, one genetic factor influenced the various dimensions of anxiety, and a second factor influenced depression; in adolescence genetic factors appeared to be shared across internalizing symptoms; and in young adulthood data supported one factor for depression and anxiety symptoms, and a second genetic factor underlying fear. Recent reviews by Maron et al (2010) and Shimada-Sugimoto et al (2015) provide synopses of efforts to identify specific genes implicated in the inter-generational transmission of anxiety, focused mainly on panic disorder.…”

Genome-wide association study of response to cognitive–behavioural therapy in children with anxiety disorders

“…11 A detailed review of the genetics of anxiety disorders is available elsewhere. 12 In brief, one variant, rs7309727 ( TMEM132D) , was associated with panic disorder in a cohort of European ancestry ( P = 1.1 × 10 −8 , odds ratio (OR) = 1.45 (95% CI 1.20–1.72). 13 A variant in the TMEM16B gene was reported at genome-wide significance in a Japanese cohort with panic disorder, but was not significant in replication analyses.…”

“…17 No significant findings from the anxiety literature to date had previously been considered in candidate gene studies. 12 …”

Genetic polymorphisms associated with common symptoms experienced by breast cancer patients

“…Recent data also suggest that an individual's genetics play an important role in the development of anxiety disorders [77][78][79][80]. Additionally, the link between the development of anxiety and inflammatory signalling pathways has also been established [69,81].…”