The genetic association between personality and major depressi0on or bipolar disorder. A polygenic score analysis using genome-wide association data

C. M. Middeldorp, M. H M De Moor, L. M. McGrath, S. D. Gordon, D. H. Blackwood, Paul Costa, A. Terracciano, R. F. Krueger, E. J C De Geus, D. R. Nyholt, T. Tanaka, T. Esko, P. A F Madden, J. Derringer, N. Amin, G. Willemsen, J. J. Hottenga, M. A. Distel, M. Uda, S. Sanna & 41 others P. Spinhoven, C. A. Hartman, S. Ripke, P. F. Sullivan, A. Realo, J. Allik, A. C. Heath, M. L. Pergadia, A. Agrawal, P. Lin, R. A. Grucza, E. Widen, D. L. Cousminer, J. G. Eriksson, A. Palotie, J. H. Barnett, P. H. Lee, 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, N. R. Wray, C. M. Van Duijn, J. W. Smoller, B. W J H Penninx, D. I. Boomsma

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere50
JournalTranslational Psychiatry
Volume1
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Bipolar Disorder
Major Depressive Disorder
Personality
Information Services
Genetic Association Studies
Mood Disorders
Single Nucleotide Polymorphism
Meta-Analysis
Logistic Models
Alleles
Regression Analysis
Neuroticism

Keywords

  • bipolar disorder
  • genetic correlation
  • genome-wide association
  • personality-major depression
  • polygenic score analysis

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience

Cite this

The genetic association between personality and major depressi0on or bipolar disorder. A polygenic score analysis using genome-wide association data. / Middeldorp, C. M.; De Moor, M. H M; McGrath, L. M.; Gordon, S. D.; Blackwood, D. H.; Costa, Paul; Terracciano, A.; Krueger, R. F.; De Geus, E. J C; Nyholt, D. R.; Tanaka, T.; 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.; Ripke, S.; Sullivan, P. F.; Realo, A.; Allik, J.; Heath, A. C.; Pergadia, M. L.; Agrawal, A.; Lin, P.; Grucza, R. A.; Widen, E.; Cousminer, D. L.; Eriksson, J. G.; Palotie, A.; Barnett, J. H.; Lee, P. H.; 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.; Räikkönen, K.; Bierut, L. J.; Martin, N. G.; Wray, N. R.; Van Duijn, C. M.; Smoller, J. W.; Penninx, B. W J H; Boomsma, D. I.

In: Translational Psychiatry, Vol. 1, e50, 2011.

Research output: Contribution to journalArticle

Middeldorp, CM, De Moor, MHM, McGrath, LM, Gordon, SD, Blackwood, DH, Costa, P, Terracciano, A, Krueger, RF, De Geus, EJC, Nyholt, DR, Tanaka, T, Esko, T, Madden, PAF, Derringer, J, Amin, N, Willemsen, G, Hottenga, JJ, 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 2011, 'The genetic association between personality and major depressi0on or bipolar disorder. A polygenic score analysis using genome-wide association data', Translational Psychiatry, vol. 1, e50. https://doi.org/10.1038/tp.2011.45
Middeldorp, C. M. ; De Moor, M. H M ; McGrath, L. M. ; Gordon, S. D. ; Blackwood, D. H. ; Costa, Paul ; Terracciano, A. ; Krueger, R. F. ; De Geus, E. J C ; Nyholt, D. R. ; Tanaka, T. ; 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. ; Ripke, S. ; Sullivan, P. F. ; Realo, A. ; Allik, J. ; Heath, A. C. ; Pergadia, M. L. ; Agrawal, A. ; Lin, P. ; Grucza, R. A. ; Widen, E. ; Cousminer, D. L. ; Eriksson, J. G. ; Palotie, A. ; Barnett, J. H. ; Lee, P. H. ; 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. ; Räikkönen, K. ; Bierut, L. J. ; Martin, N. G. ; Wray, N. R. ; Van Duijn, C. M. ; Smoller, J. W. ; Penninx, B. W J H ; Boomsma, D. I. / The genetic association between personality and major depressi0on or bipolar disorder. A polygenic score analysis using genome-wide association data. In: Translational Psychiatry. 2011 ; Vol. 1.
@article{705aededcfb3468b94b2fb183cda4d19,
title = "The genetic association between personality and major depressi0on or bipolar disorder. A polygenic score analysis using genome-wide association data",
abstract = "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.",
keywords = "bipolar disorder, genetic correlation, genome-wide association, personality-major depression, polygenic score analysis",
author = "Middeldorp, {C. M.} and {De Moor}, {M. H M} and McGrath, {L. M.} and Gordon, {S. D.} and Blackwood, {D. H.} and Paul Costa and A. Terracciano and Krueger, {R. F.} and {De Geus}, {E. J C} and Nyholt, {D. R.} and T. Tanaka and T. Esko and Madden, {P. A F} and J. Derringer and N. Amin and G. Willemsen and Hottenga, {J. J.} and Distel, {M. A.} and M. Uda and S. Sanna and P. Spinhoven and Hartman, {C. A.} and S. Ripke and Sullivan, {P. F.} and A. Realo and J. Allik and Heath, {A. C.} and Pergadia, {M. L.} and A. Agrawal and P. Lin and Grucza, {R. A.} and E. Widen and Cousminer, {D. L.} and Eriksson, {J. G.} and A. Palotie and Barnett, {J. H.} and Lee, {P. H.} and M. Luciano and A. Tenesa and G. Davies and Lopez, {L. M.} 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 Deary, {I. J.} and K. R{\"a}ikk{\"o}nen and Bierut, {L. J.} and Martin, {N. G.} and Wray, {N. R.} and {Van Duijn}, {C. M.} and Smoller, {J. W.} and Penninx, {B. W J H} and Boomsma, {D. I.}",
year = "2011",
doi = "10.1038/tp.2011.45",
language = "English (US)",
volume = "1",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - The genetic association between personality and major depressi0on or bipolar disorder. A polygenic score analysis using genome-wide association data

AU - Middeldorp, C. M.

AU - De Moor, M. H M

AU - McGrath, L. M.

AU - Gordon, S. D.

AU - Blackwood, D. H.

AU - Costa, Paul

AU - Terracciano, A.

AU - Krueger, R. F.

AU - De Geus, E. J C

AU - Nyholt, D. R.

AU - Tanaka, T.

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 - Ripke, S.

AU - Sullivan, P. F.

AU - Realo, A.

AU - Allik, J.

AU - Heath, A. C.

AU - Pergadia, M. L.

AU - Agrawal, A.

AU - Lin, P.

AU - Grucza, R. A.

AU - Widen, E.

AU - Cousminer, D. L.

AU - Eriksson, J. G.

AU - Palotie, A.

AU - Barnett, J. H.

AU - Lee, P. H.

AU - Luciano, M.

AU - Tenesa, A.

AU - Davies, G.

AU - Lopez, L. M.

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, I. J.

AU - Räikkönen, K.

AU - Bierut, L. J.

AU - Martin, N. G.

AU - Wray, N. R.

AU - Van Duijn, C. M.

AU - Smoller, J. W.

AU - Penninx, B. W J H

AU - Boomsma, D. I.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - bipolar disorder

KW - genetic correlation

KW - genome-wide association

KW - personality-major depression

KW - polygenic score analysis

UR - http://www.scopus.com/inward/record.url?scp=80054799096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054799096&partnerID=8YFLogxK

U2 - 10.1038/tp.2011.45

DO - 10.1038/tp.2011.45

M3 - Article

VL - 1

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

M1 - e50

ER -