Generalised Anxiety Disorder--A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression

PLoS One. 2015 Aug 14;10(8):e0134865. doi: 10.1371/journal.pone.0134865. eCollection 2015.

Abstract

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anxiety Disorders / epidemiology
  • Anxiety Disorders / genetics*
  • Diseases in Twins / epidemiology
  • Diseases in Twins / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Middle Aged
  • RNA Splicing Factors
  • RNA-Binding Proteins / genetics*
  • Stress Disorders, Traumatic, Acute / epidemiology
  • Stress Disorders, Traumatic, Acute / genetics*
  • Twins, Dizygotic / genetics
  • Twins, Monozygotic / genetics

Substances

  • RBFOX1 protein, human
  • RNA Splicing Factors
  • RNA-Binding Proteins