Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking
The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N=7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P=2 × 10-8). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed α-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N=5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders.
|Persistent URL||dx.doi.org/10.1038/tp.2011.42, hdl.handle.net/1765/34693|
|Note||Free full text at PubMed|
|Grant||This work was funded by the European Commission 7th Framework Programme; grant id fp7/201413 - European Network for Genetic and Genomic Epidemiology (ENGAGE), This work was funded by the European Commission 7th Framework Programme; grant id fp7/212111 - Biobanking and Biomolecular Resources Research Infrastructure (BBMRI), This work was funded by the European Commission 7th Framework Programme; grant id fp7/245536 - Opening Estonian Genome Project for European Research Area (OPENGENE)|
Terracciano, A, Esko, T, Sutin, A.R, de Moor, M.H.M, Meirelles, O, Zhu, G, … Abecasis, G.R. (2011). Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. Translational Psychiatry, 1, 1–8. doi:10.1038/tp.2011.42