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


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.

SUBMITTER: Davies MN 

PROVIDER: S-EPMC4537268 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Davies Matthew N MN   Verdi Serena S   Burri Andrea A   Trzaskowski Maciej M   Lee Minyoung M   Hettema John M JM   Jansen Rick R   Boomsma Dorret I DI   Spector Tim D TD  

PloS one 20150814 8


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 als  ...[more]

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