Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking

A Terracciano, T Esko, A R Sutin, M H M de Moor, O Meirelles, G Zhu, T Tanaka, I Giegling, T Nutile, A Realo, J Allik, N K Hansell, M J Wright, G W Montgomery, G Willemsen, J-J Hottenga, M Friedl, D Ruggiero, R Sorice, S SannaA Cannas, K Räikkönen, E Widen, A Palotie, J G Eriksson, F Cucca, R F Krueger, J Lahti, M Luciano, J W Smoller, C M van Duijn, G R Abecasis, D I Boomsma, M Ciullo, P T Costa, L Ferrucci, N G Martin, A Metspalu, D Rujescu, D Schlessinger, M Uda

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)e49
JournalTranslational Psychiatry
Volume1
Issue number10
DOIs
Publication statusPublished - 18 Oct 2011

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