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.

Public Health Relevance

Anxiety disorders are quite common, chronic, and disabling. Both genetic factors and exposure to environmental stress contribute to their development. The identification of the genes that play a role in their development can provide new clues to their causes and new directions for prevention and treatment research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH113665-02
Application #
9551674
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Gitik, Miri
Project Start
2017-09-01
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298