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

Transl Psychiatry. 2011 Oct 18;1(10):e49. doi: 10.1038/tp.2011.42.

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.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Australia / epidemiology
  • Baltimore / epidemiology
  • Estonia / epidemiology
  • Female
  • Finland / epidemiology
  • Genetic Variation*
  • Genome-Wide Association Study / methods*
  • Germany / epidemiology
  • Humans
  • Italy / epidemiology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Polymorphism, Single Nucleotide / genetics
  • Psychomotor Agitation / classification
  • Psychomotor Agitation / genetics*
  • Psychomotor Agitation / metabolism*
  • Young Adult
  • alpha Catenin / genetics*

Substances

  • CTNNA2 protein, human
  • alpha Catenin