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.
Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom; Translational Oncogenomics Laboratory, Centre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
Matthew N
MN
Davies
Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Serena
S
Verdi
Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Andrea
A
Burri
Social Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
Maciej
M
Trzaskowski
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America.
Minyoung
M
Lee
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America.
John M
JM
Hettema
Department of Biological Psychology, VU University Amsterdam, Neuroscience Campus, Amsterdam, the Netherlands.
Rick
R
Jansen
Department of Psychiatry, VU University Medical Center, Neuroscience Campus, Amsterdam, the Netherlands.
Dorret I
DI
Boomsma
Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Tim D
TD
Spector
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001008:Anxiety Disorders / Q000453:epidemiology / Q000235:genetics*; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*; D040701:Stress Disorders, Traumatic, Acute / Q000453:epidemiology / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins