Genome-wide association studies of anxiety spectrum phenotypes: Furthering the PGC Anxiety Disorders Working Group

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Anxiety disorders such as generalized anxiety disorder, panic disorder, and phobias are highly prevalent in the population and carry a significant burden of distress and impairment. Only a moderate proportion of patients with anxiety disorders respond adequately to current treatment interventions, and anxiety disorders are relatively understudied compared to other psychiatric syndromes. Exploring their genetic determinants will help elucidate their causes and guide research for prevention and new treatments. Research has documented roles for genetic risk factors in the development of anxiety disorders, many of which are shared with other internalizing phenotypes like depression and anxious temperament (“anxiety-spectrum”). We had conducted a preliminary genome-wide association study (GWAS) in approximately 18,000 subjects well-characterized for anxiety disorders using novel phenotypic approaches designed to capture common sources of genetic risk. We identified several genome-wide significant regions and polygenic risk variation associated with these phenotypes. The purpose of this current application is to facilitate expanded GWAS of the anxiety disorders. We will conduct GWAS in data from over 100,000 subjects, dissect the effects of shared versus disorder-specific genetic risk, and expand the phenotypes to include depressive disorders and anxious temperament. The Psychiatric Genomics Consortium (PGC) has achieved enormous progress in GWAS of psychiatric disorders, but they have not thus far focused on the primary ADs. The recent establishment of the PGC Anxiety Disorders Working Group will greatly facilitate accomplishment of the aims of this project, filling a major gap in psychiatric genetics research. This study will provide new insights into genetic mechanisms underlying the development of anxiety-spectrum disorders.