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

39 Scopus citations

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

Bibliographical note

Funding Information:
Acknowledgements. We thank study subjects for their participation as well as everybody involved in each of the participating studies. EGCUT authors want to acknowledge EGCUT personnel, especially Merli Hass, Viljo Soo and Mari Nelis. EGCUT data analyzes were carried out in part in the High Performance Computing Center of University of Tartu. Cilento authors acknowledge Dr Maria Enza Amendola for the test administration and thank the personnel working in the organization of the study in the villages. QIMR thanks study participants and acknowledges Nathan Gillespie for discussion on study design related to NEO collection; Marisa Grimmer, Romana Leisser and Kim Eldridge for overseeing data collection; Anjali Henders, Megan Campbell, Lisa Bowdler, Steven Crooks and staff of the Molecular Epidemiology Laboratory for sample processing and preparation; and Harry Beeby, David Smyth and Daniel Park for IT support. We acknowledge Drs Dale R Nyholt and Scott Gordon for their substantial efforts involving the QC and preparation of the GWA data sets and Dr Sarah Medland for undertaking the imputation of the GWAS data and subsequent preparation for analyses. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Anu Realo and Jüri Allik were supported by a grant from the Estonian Ministry of Science and Education (SF0180029s08) and by a Primus Grant (3-8.2/60) from the European Social Fund. TE and AM received support from FP7 Grants (201413, 212111, 245536). TE and AM also received targeted financing from Estonian Government SF0180142s08 and from the European Union through the European Regional Development Fund, in the frame of Centre of Excellence in Genomics. QIMR received support from Beyond Blue and the Borderline Personality Disorder Research Foundation. Genotyping was funded by the National Health and Medical Research Council (Medical Bioinformatics Genomics Proteomics Program, 389891). Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, European Science Foundation (EUROSTRESS), Ministry of Education, Ahokas Foundation and Emil Aaltonen Foundation.

Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.

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