Browsing by Author "Terracciano, A"

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    Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking.
    (Translational psychiatry, 2011-10-18) 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.
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    The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data.
    (Translational psychiatry, 2011-10-18) Middeldorp, CM; de Moor, MHM; McGrath, LM; Gordon, SD; Blackwood, DH; Costa, PT; Terracciano, A; Krueger, RF; de Geus, EJC; Nyholt, DR; Tanaka, T; Esko, T; Madden, PAF; Derringer, J; Amin, N; Willemsen, G; Hottenga, J-J; Distel, MA; Uda, M; Sanna, S; Spinhoven, P; Hartman, CA; Ripke, S; Sullivan, PF; Realo, A; Allik, J; Heath, AC; Pergadia, ML; Agrawal, A; Lin, P; Grucza, RA; Widen, E; Cousminer, DL; Eriksson, JG; Palotie, A; Barnett, JH; Lee, PH; Luciano, M; Tenesa, A; Davies, G; Lopez, LM; Hansell, NK; Medland, SE; Ferrucci, L; Schlessinger, D; Montgomery, GW; Wright, MJ; Aulchenko, YS; Janssens, ACJW; Oostra, BA; Metspalu, A; Abecasis, GR; Deary, IJ; Räikkönen, K; Bierut, LJ; Martin, NG; Wray, NR; van Duijn, CM; Smoller, JW; Penninx, BWJH; Boomsma, DI
    The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13,835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case-Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.