Gwas Studies in Anxiety Disorders

Overall Abstract Molecular genetic studies in anxiety disorders started approximately 25 years ago with classical linkage studies in panic disorder. Several significant or putative linkage loci have been proposed without, however, leading to the identification of specific risk genes. In the following 20 years numerous candidate gene association studies have been performed with metanalyses demonstrating significant association findings for a few genes such as COMT, MAO-A and TMEM132D. With some delay in comparison with other disorders, genome wide studies have been performed over the last 5 years. They have resulted in collaborative efforts such as the ANGST consortium. Data of a metaanalysis of more than 18 000 individuals resulted in genome-wide significant findings for case-control contrast in a non-coding RNA locus on chromosome 3q12.3 and for phenotypic factor scores within CAMKMT on chromosome 2p21 will be presented by Nick Martin for the ANGST consortium. A suggestive genome-wide finding on TMEM132D in a German Panic disorder cohort reached genome-wide signifincance in the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls. This is currently being followed up by Johannes Schumacher and coworkers in a genome-wide association study in a European Panic Disorder sample of approximately 2500 affected and 2500 control individuals. In children, genome-wide analyses of therapy response by the group of Thalia Eley provided suggestive significance for individual variants and a polgenic risk score significantly modifying therapy response. Complementing studies on categorical phenotypes, a genome-wide association study has been performed in more than 1500 individuals of the German collaborative research center on fear, anxiety and anxiety disorders by Juergen Deckert and coworkers with a genome-wide significant finding on a dimensional anxiety phenotype. These efforts of different networks demonstrate that genome-wide significant findings can be obtained in anxiety disorders. Combining them in a psychiatric genomic consortium will bring progress in the genetics of anxiety disorders to the level of other disorders and in cross-categorical comparisons will contribute to the dissection of categorical as well as dimensional psychiatric phenotypes.