Meta-analysis of genome-wide association studies for personality

de Moor, M. H. M., Costa, P. T., Terracciano, A., Krueger, R. F., de Geus, E. J. C., Toshiko, T., Penninx, B. W. J. H., Esko, T., Madden, P. A. F., Derringer, J., Amin, N., Willemsen, G., Hottenga, J.-J., Distel, M. A., Uda, M., Sanna, S., Spinhoven, P., Hartman, C. A., Sullivan, P., Realo, A., Allik, J., Heath, A. C., Pergadia, M. L., Agrawal, A., Lin, P., Grucza, R., Nutile, T., Ciullo, M., Rujescu, D., Giegling, I., Konte, B., Widen, E., Cousminer, D. L., Eriksson, J. G., Palotie, A., Peltonen, L., Luciano, M., Tenesa, A., Davies, G., Lopez, L. M., Hansell, N. K., Medland, S. E., Ferrucci, L., Schlessinger, D., Montgomery, G. W., Wright, M. J., Aulchenko, Y. S., Janssens, A. C. J. W., Oostra, B. A., Metspalu, A., Abecasis, G. R., Deary, I. J., Raikkonen, K., Bierut, L. J., Martin, N. G., van Duijn, C. M. and Boomsma, D. I. (2012) Meta-analysis of genome-wide association studies for personality. Molecular Psychiatry, 17 3: 337-349. doi:10.1038/mp.2010.128


Author de Moor, M. H. M.
Costa, P. T.
Terracciano, A.
Krueger, R. F.
de Geus, E. J. C.
Toshiko, T.
Penninx, B. W. J. H.
Esko, T.
Madden, P. A. F.
Derringer, J.
Amin, N.
Willemsen, G.
Hottenga, J.-J.
Distel, M. A.
Uda, M.
Sanna, S.
Spinhoven, P.
Hartman, C. A.
Sullivan, P.
Realo, A.
Allik, J.
Heath, A. C.
Pergadia, M. L.
Agrawal, A.
Lin, P.
Grucza, R.
Nutile, T.
Ciullo, M.
Rujescu, D.
Giegling, I.
Konte, B.
Widen, E.
Cousminer, D. L.
Eriksson, J. G.
Palotie, A.
Peltonen, L.
Luciano, M.
Tenesa, A.
Davies, G.
Lopez, L. M.
Hansell, N. K.
Medland, S. E.
Ferrucci, L.
Schlessinger, D.
Montgomery, G. W.
Wright, M. J.
Aulchenko, Y. S.
Janssens, A. C. J. W.
Oostra, B. A.
Metspalu, A.
Abecasis, G. R.
Deary, I. J.
Raikkonen, K.
Bierut, L. J.
Martin, N. G.
van Duijn, C. M.
Boomsma, D. I.
Title Meta-analysis of genome-wide association studies for personality
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
1476-5578
Publication date 2012-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1038/mp.2010.128
Open Access Status Not yet assessed
Volume 17
Issue 3
Start page 337
End page 349
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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 similar to 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 x 10(-8) and 3.1 x 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P = 4.9 x 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. Molecular Psychiatry (2012) 17, 337-349; doi: 10.1038/mp.2010.128; published online 21 December 2010
Formatted 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, P2.8 × 10 -8 and 3.1 × 10 -8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P4.9 × 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.
Keyword Personality
Five-Factor Model
Genetic variants
Meta-analysis
Genome-wide association
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NWO 480-05-003
NO1-AG-1-2109
575-25-006
56-464-14192
311-60008
R01 MH059160
10-000-1002
018947
U01 HG004422
U01 HG004446
U10 AA008401
P01 CA089392
R01 DA013423
U01HG004438
HHSN268200782096C
U10AA008401
CA89392
HHSN271200477471C
HHSN268200782096
120315
89061/Z/09/Z
DA019951
A7960034
SF0180142s08
SF0180029s08
EU/QLRT-2001-01254
201413 ENGAGE
212111 BBMRI
205419
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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