Meta-analysis of genome-wide association studies for personality

M H M de Moor; 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; Michelle Luciano; A Tenesa; Gail Davies; Lorna 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; Ian Deary; K Räikkönen; L J Bierut; N G Martin; C M van Duijn; D I Boomsma

doi:10.1038/mp.2010.128

Meta-analysis of genome-wide association studies for personality

M H M de Moor, 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 RealoJ 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, Michelle Luciano, A Tenesa, Gail Davies, Lorna 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, Ian Deary, K Räikkönen, L J Bierut, N G Martin, C M van Duijn, D I Boomsma

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

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.

Original language	English
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 - Mar 2012

Keywords

Adenosine Triphosphatases
Adult
Aged
Australia
Chromosomes, Human
Computer Simulation
Europe
European Continental Ancestry Group
Exploratory Behavior
Female
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Models, Psychological
Personality
Personality Inventory
Phenotype
Polymorphism, Single Nucleotide
Sampling Studies
United States

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A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921
Deary, I., Bates, T., Gow, A. & Starr, J.
UK central government bodies/local authorities, health and hospital authorities
1/01/11 → 31/12/12
Project: Research
Disconnected Mind [Phase 2]
Wardlaw, J.
UK-based charities
1/01/11 → 31/03/16
Project: Research
A genome wide association study of non pathological cognitive ageing
Deary, I., Porteous, D. & Tenesa, A.
BBSRC
1/09/08 → 31/08/10
Project: Research

Cite this

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., ... Boomsma, D. I. (2012). Meta-analysis of genome-wide association studies for personality. Molecular Psychiatry, 17(3), 337-349. https://doi.org/10.1038/mp.2010.128

@article{016ad063c25e4f6395d5f5354f1c574a,

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 ≈ 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.",

keywords = "Adenosine Triphosphatases, Adult, Aged, Australia, Chromosomes, Human, Computer Simulation, Europe, European Continental Ancestry Group, Exploratory Behavior, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Models, Psychological, Personality, Personality Inventory, Phenotype, Polymorphism, Single Nucleotide, Sampling Studies, United States",

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

year = "2012",

month = mar,

doi = "10.1038/mp.2010.128",

language = "English",

volume = "17",

pages = "337--349",

journal = "Molecular Psychiatry",

issn = "1359-4184",

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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, J-J, 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, L, Hansell, NK, Medland, SE, Ferrucci, L, Schlessinger, D, Montgomery, GW, Wright, MJ, Aulchenko, YS, Janssens, ACJW, Oostra, BA, Metspalu, A, Abecasis, GR, Deary, I, Räikkönen, K, Bierut, LJ, Martin, NG, van Duijn, CM & 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

TY - JOUR

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

AU - de Moor, M H M

AU - Costa, P T

AU - Terracciano, A

AU - Krueger, R F

AU - de Geus, E J C

AU - Toshiko, T

AU - Penninx, B W J H

AU - Esko, T

AU - Madden, P A F

AU - Derringer, J

AU - Amin, N

AU - Willemsen, G

AU - Hottenga, J-J

AU - Distel, M A

AU - Uda, M

AU - Sanna, S

AU - Spinhoven, P

AU - Hartman, C A

AU - Sullivan, P

AU - Realo, A

AU - Allik, J

AU - Heath, A C

AU - Pergadia, M L

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, D L

AU - Eriksson, J G

AU - Palotie, A

AU - Peltonen, L

AU - Luciano, Michelle

AU - Tenesa, A

AU - Davies, Gail

AU - Lopez, Lorna

AU - Hansell, N K

AU - Medland, S E

AU - Ferrucci, L

AU - Schlessinger, D

AU - Montgomery, G W

AU - Wright, M J

AU - Aulchenko, Y S

AU - Janssens, A C J W

AU - Oostra, B A

AU - Metspalu, A

AU - Abecasis, G R

AU - Deary, Ian

AU - Räikkönen, K

AU - Bierut, L J

AU - Martin, N G

AU - van Duijn, C M

AU - Boomsma, D I

PY - 2012/3

Y1 - 2012/3

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 ≈ 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.

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 ≈ 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.

KW - Adenosine Triphosphatases

KW - Adult

KW - Aged

KW - Australia

KW - Chromosomes, Human

KW - Computer Simulation

KW - Europe

KW - European Continental Ancestry Group

KW - Exploratory Behavior

KW - Female

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Models, Psychological

KW - Personality

KW - Personality Inventory

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Sampling Studies

KW - United States

U2 - 10.1038/mp.2010.128

DO - 10.1038/mp.2010.128

M3 - Article

C2 - 21173776

VL - 17

SP - 337

EP - 349

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 3

ER -

Meta-analysis of genome-wide association studies for personality

Abstract

Keywords

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Projects

A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921

Disconnected Mind [Phase 2]

A genome wide association study of non pathological cognitive ageing

Cite this