Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2011 Oct 18;1(10):e50.
doi: 10.1038/tp.2011.45.

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

C M Middeldorp  1 , M H M de Moor, L M McGrath, S D Gordon, D H Blackwood, P T 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, 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
Affiliations
Multicenter Study

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

C M Middeldorp et al. Transl Psychiatry. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Explained variance by the five personality traits polygenic scores in MDD in GAIN-MDD + MDD2000+, *P<0.05. MDD, major depressive disorder.
Figure 2
Figure 2
Explained variance by the five personality traits polygenic scores in BD STEP-BD+WTCCC, *P<0.05. BD, bipolar disorder; STEP-BD, Systematic Treatment Enhancement Program for Bipolar Disorder; WTCCC, Wellcome Trust Case–Control Consortium.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.
    van den Berg SM, de Moor MH, Verweij KJ, Krueger RF, Luciano M, Arias Vasquez A, Matteson LK, Derringer J, Esko T, Amin N, Gordon SD, Hansell NK, Hart AB, Seppälä I, Huffman JE, Konte B, Lahti J, Lee M, Miller M, Nutile T, Tanaka T, Teumer A, Viktorin A, Wedenoja J, Abdellaoui A, Abecasis GR, Adkins DE, Agrawal A, Allik J, Appel K, Bigdeli TB, Busonero F, Campbell H, Costa PT, Smith GD, Davies G, de Wit H, Ding J, Engelhardt BE, Eriksson JG, Fedko IO, Ferrucci L, Franke B, Giegling I, Grucza R, Hartmann AM, Heath AC, Heinonen K, Henders AK, Homuth G, Hottenga JJ, Iacono WG, Janzing J, Jokela M, Karlsson R, Kemp JP, Kirkpatrick MG, Latvala A, Lehtimäki T, Liewald DC, Madden PA, Magri C, Magnusson PK, Marten J, Maschio A, Mbarek H, Medland SE, Mihailov E, Milaneschi Y, Montgomery GW, Nauck M, Nivard MG, Ouwens KG, Palotie A, Pettersson E, Polasek O, Qian Y, Pulkki-Råback L, Raitakari OT, Realo A, Rose RJ, Ruggiero D, Schmidt CO, Slutske WS, Sorice R, Starr JM, St Pourcain B, Sutin AR, Timpson NJ, Trochet H, Vermeulen S, Vuoksimaa E, Widen E, Wouda J, Wright MJ, Zgaga L; Generation Scotland; Porteous D, Minelli A, Palmer AA, Rujescu D, Ciullo M, Hayward C, Rudan I, Metspalu A, Kaprio… See abstract for full author list ➔ van den Berg SM, et al. Behav Genet. 2016 Mar;46(2):170-82. doi: 10.1007/s10519-015-9735-5. Epub 2015 Sep 11. Behav Genet. 2016. PMID: 26362575 Free PMC article.
  • Polygenic risk scores for smoking: predictors for alcohol and cannabis use?
    Vink JM, Hottenga JJ, de Geus EJ, Willemsen G, Neale MC, Furberg H, Boomsma DI. Vink JM, et al. Addiction. 2014 Jul;109(7):1141-51. doi: 10.1111/add.12491. Epub 2014 Mar 18. Addiction. 2014. PMID: 24450588 Free PMC article.
  • Polygenic risk score: use in migraine research.
    Chalmer MA, Esserlind AL, Olesen J, Hansen TF. Chalmer MA, et al. J Headache Pain. 2018 Apr 5;19(1):29. doi: 10.1186/s10194-018-0856-0. J Headache Pain. 2018. PMID: 29623444 Free PMC article. Review.
  • Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank.
    Gale CR, Hagenaars SP, Davies G, Hill WD, Liewald DC, Cullen B, Penninx BW; International Consortium for Blood Pressure GWAS, CHARGE Consortium Aging and Longevity Group; Boomsma DI, Pell J, McIntosh AM, Smith DJ, Deary IJ, Harris SE. Gale CR, et al. Transl Psychiatry. 2016 Apr 26;6(4):e791. doi: 10.1038/tp.2016.56. Transl Psychiatry. 2016. PMID: 27115122 Free PMC article.
  • Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders.
    Ligthart L, Hottenga JJ, Lewis CM, Farmer AE, Craig IW, Breen G, Willemsen G, Vink JM, Middeldorp CM, Byrne EM, Heath AC, Madden PA, Pergadia ML, Montgomery GW, Martin NG, Penninx BW, McGuffin P, Boomsma DI, Nyholt DR. Ligthart L, et al. Hum Genet. 2014 Feb;133(2):173-86. doi: 10.1007/s00439-013-1370-8. Epub 2013 Oct 1. Hum Genet. 2014. PMID: 24081561 Free PMC article.
See all "Cited by" articles

References

    1. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 4th Edition4th edn.APA: Washington DC; 1994
    1. Costa PT, McCrae R. Manual for the Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) Psychological Assessment Resources: Odessa; 1992.
    1. Eysenck HJ, Eysenck SBG. Manual of the Eysenck Personality Questionnaire. Educational and Industrial Testing Service: San Diego, CA; 1975.
    1. Kotov R, Gamez W, Schmidt F, Watson D. Linking ‘big' personality traits to anxiety, depressive, and substance use disorders: a meta-analysis. Psychol Bull. 2010;136:768–821. - PubMed
    1. Bagby RM, Bindseil KD, Schuller DR, Rector NA, Young LT, Cooke RG, et al. Relationship between the five-factor model of personality and unipolar, bipolar and schizophrenic patients. Psychiatry Res. 1997;70:83–94. - PubMed

Publication types

Grants and funding