Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

Michelle Luciano; Saskia P. Hagenaars; Gail Davies; W David Hill; Toni-Kim Clarke; Masoud Shirali; Sarah E. Harris; Riccardo E. Marioni; David C. Liewald; Chloe Fawns-Ritchie; Mark J. Adams; David M. Howard; Cathryn M. Lewis; Catharine R. Gale; Andrew M. McIntosh; Ian Deary

doi:10.1038/s41588-017-0013-8

Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

Michelle Luciano, Saskia P. Hagenaars, Gail Davies, W David Hill, Toni-Kim Clarke, Masoud Shirali, Sarah E. Harris, Riccardo E. Marioni, David C. Liewald, Chloe Fawns-Ritchie, Mark J. Adams, David M. Howard, Cathryn M. Lewis, Catharine R. Gale, Andrew M. McIntosh, Ian Deary

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

Abstract / Description of output

Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt); heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%. Increased neuroticism is associated with poorer mental and physical health, translating to high economic burden. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (r_g = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; r_g = 0.69, s.e. = 0.07) and subjective well-being (r_g = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.

Original language	English
Pages (from-to)	6-11
Number of pages	6
Journal	Nature Genetics
Volume	50
Early online date	18 Dec 2017
DOIs	https://doi.org/10.1038/s41588-017-0013-8
Publication status	Published - 31 Jan 2018

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LucianoEtalNG2017AssociationAnalysisInOver329000Accepted author manuscript, 2.27 MB

The Disconnected Mind Phase 3
Wardlaw, J.
UK-based charities
1/04/16 → 30/09/20
Project: Research
Stratifying Resilience and Depression Longitudinally
McIntosh, A., Deary, I., Evans, K., Haley, C. & Porteous, D.
UK-based charities
1/01/15 → 30/06/21
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, P., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
Project: Research

Data supporting Luciano et al. Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism
Marioni, R. (Creator), Harris, S. (Creator), Luciano, M. (Creator), Shirali, M. (Creator), Hill, D. (Creator), Hagenaars, S. (Creator), Liewald, D. (Creator), Lewis, C. M. (Creator), McIntosh, A. (Creator), Deary, I. (Creator), Gale, C. (Creator), Adams, M. (Creator), Fawns-Ritchie, C. (Creator), Davies, G. (Creator), Clarke, T. (Creator) & Howard, D. (Creator), Edinburgh DataShare, 4 Jun 2019
DOI: 10.7488/ds/2565
Dataset

Gail Davies
- gail.daviesed.acuk
- School of Philosophy, Psychology and Language Sciences - Senior Research Fellow
- Edinburgh Neuroscience
Person: Academic: Research Active (Research Assistant)
Michelle Luciano
- michelle.lucianoed.acuk
- School of Philosophy, Psychology and Language Sciences - Personal Chair of Behavioural Genetics
- Edinburgh Neuroscience
Person: Academic: Research Active
Andrew McIntosh
- Deanery of Clinical Sciences - Chair of Biological Psychiatry
- Centre for Clinical Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active

Cite this

Luciano, M., Hagenaars, S. P., Davies, G., Hill, W. D., Clarke, T.-K., Shirali, M., Harris, S. E., Marioni, R. E., Liewald, D. C., Fawns-Ritchie, C., Adams, M. J., Howard, D. M., Lewis, C. M., Gale, C. R., McIntosh, A. M., & Deary, I. (2018). Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism. Nature Genetics, 50, 6-11. https://doi.org/10.1038/s41588-017-0013-8

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title = "Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism",

abstract = "Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt); heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%. Increased neuroticism is associated with poorer mental and physical health, translating to high economic burden. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.",

author = "Michelle Luciano and Hagenaars, {Saskia P.} and Gail Davies and Hill, {W David} and Toni-Kim Clarke and Masoud Shirali and Harris, {Sarah E.} and Marioni, {Riccardo E.} and Liewald, {David C.} and Chloe Fawns-Ritchie and Adams, {Mark J.} and Howard, {David M.} and Lewis, {Cathryn M.} and Gale, {Catharine R.} and McIntosh, {Andrew M.} and Ian Deary",

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doi = "10.1038/s41588-017-0013-8",

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Luciano, M, Hagenaars, SP, Davies, G , Hill, WD, Clarke, T-K, Shirali, M, Harris, SE , Marioni, RE, Liewald, DC, Fawns-Ritchie, C , Adams, MJ, Howard, DM, Lewis, CM, Gale, CR, McIntosh, AM & Deary, I 2018, 'Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism', Nature Genetics, vol. 50, pp. 6-11. https://doi.org/10.1038/s41588-017-0013-8

TY - JOUR

T1 - Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

AU - Luciano, Michelle

AU - Hagenaars, Saskia P.

AU - Davies, Gail

AU - Hill, W David

AU - Clarke, Toni-Kim

AU - Shirali, Masoud

AU - Harris, Sarah E.

AU - Marioni, Riccardo E.

AU - Liewald, David C.

AU - Fawns-Ritchie, Chloe

AU - Adams, Mark J.

AU - Howard, David M.

AU - Lewis, Cathryn M.

AU - Gale, Catharine R.

AU - McIntosh, Andrew M.

AU - Deary, Ian

PY - 2018/1/31

Y1 - 2018/1/31

N2 - Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt); heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%. Increased neuroticism is associated with poorer mental and physical health, translating to high economic burden. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.

AB - Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt); heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%. Increased neuroticism is associated with poorer mental and physical health, translating to high economic burden. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.

U2 - 10.1038/s41588-017-0013-8

DO - 10.1038/s41588-017-0013-8

M3 - Article

SN - 1061-4036

VL - 50

SP - 6

EP - 11

JO - Nature Genetics

JF - Nature Genetics

ER -

Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

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Projects

The Disconnected Mind Phase 3

Stratifying Resilience and Depression Longitudinally

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

Datasets

Data supporting Luciano et al. Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

Profiles

Gail Davies

Michelle Luciano

Andrew McIntosh

Cite this