Literature DB >> 21173776

Meta-analysis of genome-wide association studies for personality.

M H M de Moor1, P T Costa, A Terracciano, R F Krueger, E J C de Geus, T Toshiko, B W J H Penninx, T Esko, P A F Madden, J Derringer, N Amin, G Willemsen, J-J Hottenga, M A Distel, M Uda, S Sanna, P Spinhoven, C A Hartman, P Sullivan, A Realo, J Allik, A C Heath, M L Pergadia, A Agrawal, P Lin, R Grucza, T Nutile, M Ciullo, D Rujescu, I Giegling, B Konte, E Widen, D L Cousminer, J G Eriksson, A Palotie, L Peltonen, M Luciano, A Tenesa, G Davies, L M Lopez, N K Hansell, S E Medland, L Ferrucci, D Schlessinger, G W Montgomery, M J Wright, Y S Aulchenko, A C J W Janssens, B A Oostra, A Metspalu, G R Abecasis, I J Deary, K Räikkönen, L J Bierut, N G Martin, C M van Duijn, D I Boomsma.   

Abstract

Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17,375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ≈ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10(-8) and 3.1 × 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10(-8)). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

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Year:  2010        PMID: 21173776      PMCID: PMC3785122          DOI: 10.1038/mp.2010.128

Source DB:  PubMed          Journal:  Mol Psychiatry        ISSN: 1359-4184            Impact factor:   15.992


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