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

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. In our first funding period, we built the foundation for conducting sufficiently powered genome-wide association study (GWAS) meta-analyses for the anxiety disorders through the newly established Anxiety Disorders Working Group of the Psychiatric Genetics Consortium (PGC-ANX). We assembled data from 36 European ancestry cohorts totaling 122K composite ANX cases and 730K controls. We performed case-control SNP- and gene-based analyses and identified genome-wide significant associations in 58 independent SNPs and 91 genes, respectively. The purpose of this current application is to expand the sample size, identify susceptibility loci for each anxiety disorder, and extend those results beyond European ancestry individuals. We will apply these results to refine the prediction of clinical risk for anxiety. This study will provide new insights into genetic mechanisms underlying the development of anxiety disorders.