title: Further confirmation of the association between anxiety and CTNND2: replication in humans.
abstract: The rat genome sequencing and mapping consortium found evidence for an association between the catenin-δ2 gene (CTNND2) and anxious behaviour. We replicated these results in humans by carrying out a genetic association test in patients with panic disorder, social phobia, generalized anxiety disorder and/or agoraphobia (N = 1714) and controls (N = 4125). We further explored the association between CTNND2 and other psychiatric disorders based on publicly available genome-wide association results. A gene-based test showed that single nucleotide polymorphisms (SNPs) in CTNND2 have a significantly increased signal (P < 1e(-5) ) and decreased P-values. Single nucleotide polymorphism rs1012176 showed the strongest association with any anxiety disorder (odds ratio: 0.8128, SE = 0.063, P = 0.00099), but this effect was not significant after correction for multiple testing. In available genome-wide association results from the Psychiatric Genomics Consortium we found that SNPs in CTNND2 collectively showed an increased signal for schizophrenia (P < 1e(-5) ) and major depressive disorder (P < 1e(-5) ), but not for bipolar disorder. These signals remained significant after correction for potential confounders. The association between CTNND2 and anxiety was not strong enough to be picked up in the current generation of human genome-wide analyses, indicating the usefulness of and need for animal genetic studies to identify candidate genes for further study in human samples.
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands; Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, the Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Nivard
authors.forename: H
authors.initials: H
authors.lastname: Mbarek
authors.forename: J J
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: J H
authors.initials: JH
authors.lastname: Smit
authors.forename: R
authors.initials: R
authors.lastname: Jansen
authors.forename: B W
authors.initials: BW
authors.lastname: Penninx
authors.forename: C M
authors.initials: CM
authors.lastname: Middeldorp
authors.forename: D I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D001008:Anxiety Disorders / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D051177:Catenins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D000095002:Delta Catenin; C000722348:CTNND2 protein, human
keywords: Anxiety disorder; bipolar disorder; catenin δ2; genetic association; humans; major depression; rats; schizophrenia