Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression
pmid: 26274327
pmc: PMC4537268
Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression
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.
- George Washington University United States
- University of Amsterdam Netherlands
- University of Queensland Australia
- Amsterdam UMC Netherlands
- Vrije Universiteit Amsterdam Netherlands
Netherlands Twin Register (NTR), Adult, 1300 Biochemistry, Science, 610, Psychiatry and Psychology, Genetics and Molecular Biology, 1100 Agricultural and Biological Sciences, Diseases in Twins, Twins, Dizygotic, Humans, Genetic Predisposition to Disease, Stress Disorders, Traumatic, Acute, Aged, Aged, 80 and over, Q, R, RNA-Binding Proteins, General Medicine, Twins, Monozygotic, Middle Aged, Anxiety Disorders, Gene Expression Regulation, General Biochemistry, Medicine, Female, RNA Splicing Factors, General Agricultural and Biological Sciences, Research Article, Genome-Wide Association Study
Netherlands Twin Register (NTR), Adult, 1300 Biochemistry, Science, 610, Psychiatry and Psychology, Genetics and Molecular Biology, 1100 Agricultural and Biological Sciences, Diseases in Twins, Twins, Dizygotic, Humans, Genetic Predisposition to Disease, Stress Disorders, Traumatic, Acute, Aged, Aged, 80 and over, Q, R, RNA-Binding Proteins, General Medicine, Twins, Monozygotic, Middle Aged, Anxiety Disorders, Gene Expression Regulation, General Biochemistry, Medicine, Female, RNA Splicing Factors, General Agricultural and Biological Sciences, Research Article, Genome-Wide Association Study
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