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. Sanna & 21 others A. 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, Paul Costa, L. Ferrucci, N. G. Martin, A. Metspalu, D. Rujescu, D. Schlessinger, M. Uda

Research output: Contribution to journalArticle

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

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Unsafe Sex
Catenins
Genome-Wide Association Study
Cadherins
Meta-Analysis
Personality Inventory
Impulsive Behavior
Risk-Taking
Bipolar Disorder
Smoke
Substance-Related Disorders
Single Nucleotide Polymorphism
Personality
Proteins
Genome
Brain
Pharmaceutical Preparations
Genes
Direction compound
Drive

ASJC Scopus subject areas

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

Cite this

Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. / Terracciano, A.; Esko, T.; Sutin, A. R.; De Moor, M. H M; Meirelles, O.; Zhu, G.; Tanaka, T.; Giegling, I.; Nutile, T.; Realo, A.; Allik, J.; Hansell, N. K.; Wright, M. J.; Montgomery, G. W.; Willemsen, G.; Hottenga, J. J.; Friedl, M.; Ruggiero, D.; Sorice, R.; Sanna, S.; Cannas, A.; Räikkönen, K.; Widen, E.; Palotie, A.; Eriksson, J. G.; Cucca, F.; Krueger, R. F.; Lahti, J.; Luciano, M.; Smoller, J. W.; Van Duijn, C. M.; Abecasis, G. R.; Boomsma, D. I.; Ciullo, M.; Costa, Paul; Ferrucci, L.; Martin, N. G.; Metspalu, A.; Rujescu, D.; Schlessinger, D.; Uda, M.

In: Translational Psychiatry, Vol. 1, e49, 2011.

Research output: Contribution to journalArticle

Terracciano, A, Esko, T, Sutin, AR, De Moor, MHM, Meirelles, O, Zhu, G, Tanaka, T, Giegling, I, Nutile, T, Realo, A, Allik, J, Hansell, NK, Wright, MJ, Montgomery, GW, Willemsen, G, Hottenga, JJ, Friedl, M, Ruggiero, D, Sorice, R, Sanna, S, Cannas, A, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Cucca, F, Krueger, RF, Lahti, J, Luciano, M, Smoller, JW, Van Duijn, CM, Abecasis, GR, Boomsma, DI, Ciullo, M, Costa, P, Ferrucci, L, Martin, NG, Metspalu, A, Rujescu, D, Schlessinger, D & Uda, M 2011, 'Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking', Translational Psychiatry, vol. 1, e49. https://doi.org/10.1038/tp.2011.42
Terracciano, A. ; Esko, T. ; Sutin, A. R. ; De Moor, M. H M ; Meirelles, O. ; Zhu, G. ; Tanaka, T. ; Giegling, I. ; Nutile, T. ; Realo, A. ; Allik, J. ; Hansell, N. K. ; Wright, M. J. ; Montgomery, G. W. ; Willemsen, G. ; Hottenga, J. J. ; Friedl, M. ; Ruggiero, D. ; Sorice, R. ; Sanna, S. ; Cannas, A. ; Räikkönen, K. ; Widen, E. ; Palotie, A. ; Eriksson, J. G. ; Cucca, F. ; Krueger, R. F. ; Lahti, J. ; Luciano, M. ; Smoller, J. W. ; Van Duijn, C. M. ; Abecasis, G. R. ; Boomsma, D. I. ; Ciullo, M. ; Costa, Paul ; Ferrucci, L. ; Martin, N. G. ; Metspalu, A. ; Rujescu, D. ; Schlessinger, D. ; Uda, M. / Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. In: Translational Psychiatry. 2011 ; Vol. 1.
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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.",
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T1 - Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking

AU - Terracciano, A.

AU - Esko, T.

AU - Sutin, A. R.

AU - De Moor, M. H M

AU - Meirelles, O.

AU - Zhu, G.

AU - Tanaka, T.

AU - Giegling, I.

AU - Nutile, T.

AU - Realo, A.

AU - Allik, J.

AU - Hansell, N. K.

AU - Wright, M. J.

AU - Montgomery, G. W.

AU - Willemsen, G.

AU - Hottenga, J. J.

AU - Friedl, M.

AU - Ruggiero, D.

AU - Sorice, R.

AU - Sanna, S.

AU - Cannas, A.

AU - Räikkönen, K.

AU - Widen, E.

AU - Palotie, A.

AU - Eriksson, J. G.

AU - Cucca, F.

AU - Krueger, R. F.

AU - Lahti, J.

AU - Luciano, M.

AU - Smoller, J. W.

AU - Van Duijn, C. M.

AU - Abecasis, G. R.

AU - Boomsma, D. I.

AU - Ciullo, M.

AU - Costa, Paul

AU - Ferrucci, L.

AU - Martin, N. G.

AU - Metspalu, A.

AU - Rujescu, D.

AU - Schlessinger, D.

AU - Uda, M.

PY - 2011

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