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; 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; P. T. Costa; L. Ferrucci; N. G. Martin; A. Metspalu; D. Rujescu; D. Schlessinger; M. Uda

doi:10.1038/tp.2011.42

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

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, P. T. Costa, L. Ferrucci, N. G. Martin, A. Metspalu, D. Rujescu, D. Schlessinger, M. Uda

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

59 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 language	English
Article number	e49
Journal	Translational Psychiatry
Volume	1
DOIs	https://doi.org/10.1038/tp.2011.42
Publication status	Published - 2011
Externally published	Yes

Access to Document

10.1038/tp.2011.42

Cite this

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., ... Uda, M. (2011). Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. Translational Psychiatry, 1, Article e49. https://doi.org/10.1038/tp.2011.42

@article{eb69af1db860422083081543e5913618,

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

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.",

author = "A. Terracciano and T. Esko and Sutin, \{A. R.\} and \{De Moor\}, \{M. H.M.\} and O. Meirelles and G. Zhu and T. Tanaka and I. Giegling and T. Nutile and A. Realo and J. Allik and Hansell, \{N. K.\} and Wright, \{M. J.\} and Montgomery, \{G. W.\} and G. Willemsen and Hottenga, \{J. J.\} and M. Friedl and D. Ruggiero and R. Sorice and S. Sanna and A. Cannas and K. R{\"a}ikk{\"o}nen and E. Widen and A. Palotie and Eriksson, \{J. G.\} and F. Cucca and Krueger, \{R. F.\} and J. Lahti and M. Luciano and Smoller, \{J. W.\} and \{Van Duijn\}, \{C. M.\} and Abecasis, \{G. R.\} and Boomsma, \{D. I.\} and M. Ciullo and Costa, \{P. T.\} and L. Ferrucci and Martin, \{N. G.\} and A. Metspalu and D. Rujescu and D. Schlessinger and M. Uda",

year = "2011",

doi = "10.1038/tp.2011.42",

language = "English",

volume = "1",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

}

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, PT, 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

TY - JOUR

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, P. T.

AU - Ferrucci, L.

AU - Martin, N. G.

AU - Metspalu, A.

AU - Rujescu, D.

AU - Schlessinger, D.

AU - Uda, M.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/80054797850

U2 - 10.1038/tp.2011.42

DO - 10.1038/tp.2011.42

M3 - Article

C2 - 22833195

AN - SCOPUS:80054797850

SN - 2158-3188

VL - 1

JO - Translational Psychiatry

JF - Translational Psychiatry

M1 - e49

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this