An Association Analysis of Circadian Genes in Anxiety Disorders

Background: The mammalian circadian system is responsible for controlling daily oscillations in physiology and behavior. Circadian genes contribute to the sleep wake cycle and mood, and because patients with anxiety disorder often suffer from sleep disturbances, we hypothesized that variants in circadian-clock-related genes might predispose to human anxiety disorders as well. We tested this hypothesis with a genetic association analysis. Methods: We analyzed 131 single nucleotide polymorphisms from 13 circadian-clock-related genes. The study sample consisted of 321 individuals diagnosed with an anxiety disorder and 653 matched healthy controls from a Finnish population-based cohort. Results: Single nucleotide polymorphisms in two genes showed some evidence for association to social phobia: in ARNTL2 rs2306073 (p = .0099) and in DRD2 rs7131056 (p = .0084). BCL2 rs12454712 (p = .0029) and DRD2 rs4245146 (p = .0010) showed evidence for association to generalized anxiety disorder, whereas rs2463107 (p = .0064) in PAWR and rs4245146 (p = .0029) in DRD2 showed evidence for association to the pooled group of all anxiety disorders. Findings in DRD2 became stronger when only anxiety disorder cases with comorbid alcohol use disorder were considered. Conclusions: Genes contributing to circadian rhythms might also play a role in the genetic predisposition to anxiety disorders. In addition, our study provides further support for the association of DRD2 to comorbid anxiety and alcohol use disorder.