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.
Highlights
Genome-wide association studies (GWAS) have reliably identified common genetic variants associated with complex traits and diseases.[1,2,3,4] For personality traits, as for other psychological and psychiatric conditions, finding genomewide significant associations has been difficult,[5,6,7,8,9] presumably because of relatively small effects and sample sizes
We further tested whether any single-nucleotide polymorphisms (SNPs) significantly associated with the Excitement-Seeking scale in the meta-analysis replicated in additional samples
With a total of 7860 subjects, we found a genome-wide significant association between rs7600563, a common variant in CTNNA2 and the Revised NEO Personality Inventory Excitement-Seeking scale, a trait measure of thrill-seeking and risk-taking behaviors (P 1⁄4 2 Â 10À8)
Summary
Genome-wide association studies (GWAS) have reliably identified common genetic variants associated with complex traits and diseases.[1,2,3,4] For personality traits, as for other psychological and psychiatric conditions, finding genomewide significant associations has been difficult,[5,6,7,8,9] presumably because of relatively small effects and sample sizes. Excitement-seeking is a personality trait that reflects an individual’s tendency to crave stimulation and thrills.[13,14] This trait, akin to some aspects of sensation seeking, is a major component of the multifaceted impulsivity construct and is a core defining feature of extraversion.[13,14,15,16,17] Excitement-seeking is conceptually related to the approach-oriented motivation system and the behavioral activation system.[15,18,19,20,21] Those who score high on measures of excitement-seeking tend to engage in exciting activities, crave intense sensations, pursue a high level of arousal and are generally attracted by bright colors and crowded environments They are more likely to take unnecessary risks for thrills (for example, skydiving) and engage in risky behaviors and dangerous activities just for fun. We further tested whether any single-nucleotide polymorphisms (SNPs) significantly associated with the Excitement-Seeking scale in the meta-analysis replicated in additional samples
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