Twin data has also been used to aid in genetic association studies in the area of internalizing disorders. Using data from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, multivariate structural equation modeling was used to identify common genetic risk factors for major depression, generalized anxiety disorder, panic disorder, Tivantinib in vivo agoraphobia, social phobia, and neuroticism. Cases and controls were then identified for genetic association studies based on scoring at the extremes of the genetic factor extracted from the twin analysis, with the subsequent association analyses yielding evidence for association Inhibitors,research,lifescience,medical with the gene GAD1.30 Another area where genetic epidemiology

intersects with gene identification Inhibitors,research,lifescience,medical efforts is in the characterization of risk associated with identified genes. Most major gene identification efforts for psychiatric disorders currently focus on adult psychiatric outcomes. As we identify genes that are reliably associated with these disorders, one of the next interesting research challenges will be to study how risk associated with these genes unfolds across development and in conjunction with the environment. Here, findings from genetic epidemiology can again be useful in developing hypotheses to test the risk associated with specific genes. For example, based on the twin literature suggesting that adult alcohol Inhibitors,research,lifescience,medical dependence and

childhood externalizing symptoms overlap in large part due to a shared genetic predisposition,31 genes that were originally

identified as associated with adult alcohol dependence (eg, GABRA2,32 CHRM2 33) have been tested for association with externalizing behavior in younger samples of children and adolescents. These studies suggest that children carrying the genetic variants associated with alcohol problems later in life Inhibitors,research,lifescience,medical display elevated rates of conduct problems earlier in development, before any association with alcohol dependence has manifested.34-36 Further, based on the twin literatures suggesting that genetic influences on externalizing behaviors are moderated by parental monitoring9 and peer deviance,37,38 further analyses demonstrated Inhibitors,research,lifescience,medical that the associations between these genes and externalizing behavior were stronger under conditions of lower parental monitoring and higher peer deviance. Characterizing the risk unless pathways associated with identified genes will be critical in eventually translating this information into improved prevention and intervention programs. Gene identification methods The field of psychiatric genetics has used two different methods to attempt to identify individual risk genes: linkage and association. These are fundamentally different approaches with different study designs applied, until recently, to very different research questions. It is important to understand both in order to understand why association approaches have become the norm in followup studies of linkage regions as well as the primary current approach in genome-wide studies.