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 journalArticlepeer-review

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 (US)
Article numbere49
JournalTranslational psychiatry
Volume1
DOIs
StatePublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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