Further confirmation of the association between anxiety and CTNND2: replication in humans.
- Authors
- Nivard, M G; Mbarek, H; Hottenga, J J; Smit, J H; Jansen, R; Penninx, B W; Middeldorp, C M; Boomsma, D I
- Year
- 2014
- Journal
- Genes, brain, and behavior
- PMID
- 24256404
- DOI
- 10.1111/gbb.12095
The rat genome sequencing and mapping consortium found evidence for an association between the catenin-Ξ΄2 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 (Nβ=β1714) and controls (Nβ=β4125). 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 (Pβ<β1e(-5) ) and decreased P-values. Single nucleotide polymorphism rs1012176 showed the strongest association with any anxiety disorder (odds ratio: 0.8128, SEβ=β0.063, Pβ=β0.00099), 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 (Pβ<β1e(-5) ) and major depressive disorder (Pβ<β1e(-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.
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