A genetic contribution to psychological traits and psychiatric disorders is not in doubt, but the nature and extent of that contribution
is still unclear. Genetic epidemiology has assembled convincing evidence that anxiety and related disorders are influenced by genetic mTOR inhibitor factors and that the genetic component is highly complex. While studies of the patterns of inheritance of personality indicate that various dimensions are likely to be influenced by many genes and quantitative traits, it also documents the significance of environmental factors. As the modes of inheritance of anxiety disorders are complex, it has been concluded that multiple genes of small effect, in interaction Inhibitors,research,lifescience,medical with each other and with nongenetic Inhibitors,research,lifescience,medical neurodevelopmental events, produce vulnerability to the disorder. Segregation analysis involves fitting a general model
to the inheritance pattern of a trait in pedigrees. The only opportunity to examine the expression of a human trait in a fixed genetic background comes from the study of monozygotic (MZ) twins.3 The absolute risk to an MZ twin Inhibitors,research,lifescience,medical of an affected individual provides a direct estimate of penetrance for a given environment. Twin studies generally compare the similarity between identical (MZ) and fraternal (dizygotic [DZ]) twins. DZ twins share on average only half of their genes, as do normal sibs. A higher correlation between MZ than between DZ twins indicates a genetic influence on the trait under investigation. Twin studies of self-reported symptoms of anxiety, often called negative emotionality or neuroticism, consistently indicate that approximately 50% of the variance can be attributed to genetic factors.4-6 Tools of the trade The methods available for Inhibitors,research,lifescience,medical the genetic dissection of
complex traits, which will be referred to at various stages throughout this review, are linkage analysis, allele-sharing methods, association studies in human populations, and genetic analysis of Inhibitors,research,lifescience,medical large crosses in model organisms such as the mouse. For the purposes of this review, I will briefly summarize the methods; however, more detailed accounts abound in the literature.2,6,7 Linkage analysis is a form SB-3CT of genetic mapping that is used to find the approximate chromosomal location of a putative gene. Linkage studies are based on the identification of large families with many affected members and one is required to specify a mode of inheritance for the disorder. The inheritance of the disorder in the family is then compared with the allelic inheritance of known sections of DNA known as polymorphic markers. The coinheritance, or linkage, of a particular marker allele with the presence or absence of the disorder allows one to define or narrow down the location of the suspected gene. Thus, linkage analysis allows one to find out where a gene is, without knowing what it is.