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.
authors: National Institute on Aging, NIH, DHHS, Baltimore, MD 21224, USA. Terraccianoa@mail.nih.gov
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mesh_terms: D000293:Adolescent; D000328:Adult; D001315:Australia / Q000453:epidemiology; D015142:Baltimore / Q000453:epidemiology; D004957:Estonia / Q000453:epidemiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011595:Psychomotor Agitation / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult; D051178:alpha Catenin / Q000235:genetics*
chemical_list: C079671:CTNNA2 protein, human; D051178:alpha Catenin