Meta-analysis of genome-wide association studies for personality

MHM de Moor; PT Costa; A Terracciano; RF Krueger; EJC de Geus; T Toshiko; BWJH Penninx; T Esko; PAF Madden; J Derringer; Najaf Amin; G Willemsen; JJ (Jouke Jan) Hottenga; MA Distel; M Uda; S Sanna; P Spinhoven; CA Hartman; P Sullivan; A Realo; J Allik; AC Heath; ML Pergadia; A Agrawal; P Lin; R Grucza; T Nutile; M Ciullo; D Rujescu; I Giegling; B Konte; E Widen; DL Cousminer; JG Eriksson; A Palotie; L Peltonen; M Luciano; A Tenesa; G Davies; LM Lopez; NK Hansell; SE Medland; L Ferrucci; D Schlessinger; GW Montgomery; MJ Wright; YS Aulchenko; Cecile Janssens; Ben Oostra; A Metspalu; GR Abecasis; IJ Deary; K Raikkonen; LJ Bierut; NG Martin; Cornelia Duijn; DI Boomsma

doi:10.1038/mp.2010.128

Meta-analysis of genome-wide association studies for personality

MHM de Moor, PT Costa, A Terracciano, RF Krueger, EJC de Geus, T Toshiko, BWJH Penninx, T Esko, PAF Madden, J Derringer, Najaf Amin, G Willemsen, JJ (Jouke Jan) Hottenga, MA Distel, M Uda, S Sanna, P Spinhoven, CA Hartman, P Sullivan, A RealoJ Allik, AC Heath, ML Pergadia, A Agrawal, P Lin, R Grucza, T Nutile, M Ciullo, D Rujescu, I Giegling, B Konte, E Widen, DL Cousminer, JG Eriksson, A Palotie, L Peltonen, M Luciano, A Tenesa, G Davies, LM Lopez, NK Hansell, SE Medland, L Ferrucci, D Schlessinger, GW Montgomery, MJ Wright, YS Aulchenko, Cecile Janssens, Ben Oostra, A Metspalu, GR Abecasis, IJ Deary, K Raikkonen, LJ Bierut, NG Martin, Cornelia Duijn, DI Boomsma

Research output: Contribution to journal › Article › Academic › peer-review

239 Citations (Scopus)

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

Original language	Undefined/Unknown
Pages (from-to)	337-349
Number of pages	13
Journal	Molecular Psychiatry
Volume	17
Issue number	3
DOIs	https://doi.org/10.1038/mp.2010.128
Publication status	Published - 2012

Research programs

EMC MGC-02-96-01
EMC NIHES-01-64-02
EMC NIHES-01-64-03

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This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/mp.2010.128

http://hdl.handle.net/1765/28409

Cite this

de Moor, MHM., Costa, PT., Terracciano, A., Krueger, RF., de Geus, EJC., Toshiko, T., Penninx, BWJH., Esko, T., Madden, PAF., Derringer, J., Amin, N., Willemsen, G., Hottenga, JJ., Distel, MA., Uda, M., Sanna, S., Spinhoven, P., Hartman, CA., Sullivan, P., ... Boomsma, DI. (2012). Meta-analysis of genome-wide association studies for personality. Molecular Psychiatry, 17(3), 337-349. https://doi.org/10.1038/mp.2010.128

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title = "Meta-analysis of genome-wide association studies for personality",

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",

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de Moor, MHM, Costa, PT, Terracciano, A, Krueger, RF, de Geus, EJC, Toshiko, T, Penninx, BWJH, Esko, T, Madden, PAF, Derringer, J, Amin, N, Willemsen, G, Hottenga, JJ, Distel, MA, Uda, M, Sanna, S, Spinhoven, P, Hartman, CA, Sullivan, P, Realo, A, Allik, J, Heath, AC, Pergadia, ML, Agrawal, A, Lin, P, Grucza, R, Nutile, T, Ciullo, M, Rujescu, D, Giegling, I, Konte, B, Widen, E, Cousminer, DL, Eriksson, JG, Palotie, A, Peltonen, L, Luciano, M, Tenesa, A, Davies, G, Lopez, LM, Hansell, NK, Medland, SE, Ferrucci, L, Schlessinger, D, Montgomery, GW, Wright, MJ, Aulchenko, YS, Janssens, C, Oostra, B, Metspalu, A, Abecasis, GR, Deary, IJ, Raikkonen, K, Bierut, LJ, Martin, NG, Duijn, C & Boomsma, DI 2012, 'Meta-analysis of genome-wide association studies for personality', Molecular Psychiatry, vol. 17, no. 3, pp. 337-349. https://doi.org/10.1038/mp.2010.128

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T1 - Meta-analysis of genome-wide association studies for personality

AU - de Moor, MHM

AU - Costa, PT

AU - Terracciano, A

AU - Krueger, RF

AU - de Geus, EJC

AU - Toshiko, T

AU - Penninx, BWJH

AU - Esko, T

AU - Madden, PAF

AU - Derringer, J

AU - Amin, Najaf

AU - Willemsen, G

AU - Hottenga, JJ (Jouke Jan)

AU - Distel, MA

AU - Uda, M

AU - Sanna, S

AU - Spinhoven, P

AU - Hartman, CA

AU - Sullivan, P

AU - Realo, A

AU - Allik, J

AU - Heath, AC

AU - Pergadia, ML

AU - Agrawal, A

AU - Lin, P

AU - Grucza, R

AU - Nutile, T

AU - Ciullo, M

AU - Rujescu, D

AU - Giegling, I

AU - Konte, B

AU - Widen, E

AU - Cousminer, DL

AU - Eriksson, JG

AU - Palotie, A

AU - Peltonen, L

AU - Luciano, M

AU - Tenesa, A

AU - Davies, G

AU - Lopez, LM

AU - Hansell, NK

AU - Medland, SE

AU - Ferrucci, L

AU - Schlessinger, D

AU - Montgomery, GW

AU - Wright, MJ

AU - Aulchenko, YS

AU - Janssens, Cecile

AU - Oostra, Ben

AU - Metspalu, A

AU - Abecasis, GR

AU - Deary, IJ

AU - Raikkonen, K

AU - Bierut, LJ

AU - Martin, NG

AU - Duijn, Cornelia

AU - Boomsma, DI

PY - 2012

Y1 - 2012

N2 - 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

AB - 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

U2 - 10.1038/mp.2010.128

DO - 10.1038/mp.2010.128

M3 - Article

C2 - 21173776

SN - 1359-4184

VL - 17

SP - 337

EP - 349

JO - Molecular Psychiatry

JF - Molecular Psychiatry

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