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