Validation of candidate anxiety disorder genes using a carbon dioxide challenge task.
Few replicable genetic variants have been identified in the etiology of heritable anxiety disorders such as panic disorder. Endophenotypic measures that have reduced heterogeneity may provide more powerful targets for gene identification. We assessed hypersensitivity to carbon dioxide (a reliable endophenotype of panic and anxiety) in 174 Caucasian college students, who were genotyped on 26 polymorphic markers from 11 genes previously associated with panic/anxiety. Individual trajectories of respiratory and subjective anxiety response to carbon dioxide were measured and tested for association with these genetic markers. One marker in the acid-sensing ion channel 1 (ASIC1) gene, rs1108923, had a significant association with respiratory rate. No genes had a significant association with subjective anxiety response. Our findings support previously reported associations between ASIC1 and panic/anxiety, but not other genes previously associated with anxiety disorders. The use of endophenotypic markers is a promising avenue for gene identification in anxiety and other complex disorders.
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: savagej@vcu.edu.
Jeanne E
JE
Savage
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Omari
O
McMichael
Department of Psychology, University of Virginia, Charlottesville, VA, USA.
Eugenia I
EI
Gorlin
Department of Psychology, University of Virginia, Charlottesville, VA, USA.
Jessica R
JR
Beadel
Department of Psychology, University of Virginia, Charlottesville, VA, USA.
Bethany
B
Teachman
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA; Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, USA; Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD, USA.
Vladimir I
VI
Vladimirov
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
John M
JM
Hettema
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Roxann
R
Roberson-Nay
D062565:Acid Sensing Ion Channels / Q000235:genetics*; D000328:Adult; D001007:Anxiety / Q000235:genetics; D001008:Anxiety Disorders / Q000235:genetics*; D002245:Carbon Dioxide / Q000008:administration & dosage*; D058068:Endophenotypes; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008297:Male; D056152:Respiratory Rate / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D002245:Carbon Dioxide
ASIC1; Acid-sensing ion channel 1; Anxiety disorders; Carbon dioxide hypersensitivity; Endophenotype; Panic disorder