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

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

doi:10.1038/s41588-017-0013-8

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

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

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Abstract

Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3,4,5,6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. 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.

Original language	English
Pages (from-to)	6-11
Journal	Nature Genetics
Volume	50
Issue number	1
Early online date	18 Dec 2017
DOIs	https://doi.org/10.1038/s41588-017-0013-8
Publication status	Published - 1 Jan 2018

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Luciano, M., Hagenaars, S., Davies, G., Hill, W. D., Clarke, T.-K., Shirali, M., Harris, S. E., Marioni, R., Liewald, D. C., Fawns-Ritchie, C., Adams, M. J., Howard, D., Lewis, C., Gale, C. R., McIntosh, A. M., & Deary, I. J. (2018). Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism. Nature Genetics, 50(1), 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)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3,4,5,6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. 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 Saskia Hagenaars and Gail Davies and Hill, {W David} and Toni-Kim Clarke and Masoud Shirali and Harris, {Sarah E.} and Riccardo Marioni and Liewald, {David C.} and Chloe Fawns-Ritchie and Adams, {Mark J.} and David Howard and Cathryn Lewis and Gale, {Catharine R.} and McIntosh, {Andrew M.} and Deary, {Ian J.}",

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Luciano, M, Hagenaars, S, Davies, G, Hill, WD, Clarke, T-K, Shirali, M, Harris, SE, Marioni, R, Liewald, DC, Fawns-Ritchie, C, Adams, MJ, Howard, D , Lewis, C, Gale, CR, McIntosh, AM & Deary, IJ 2018, 'Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism', Nature Genetics, vol. 50, no. 1, pp. 6-11. https://doi.org/10.1038/s41588-017-0013-8

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AU - Luciano, Michelle

AU - Hagenaars, Saskia

AU - Davies, Gail

AU - Hill, W David

AU - Clarke, Toni-Kim

AU - Shirali, Masoud

AU - Harris, Sarah E.

AU - Marioni, Riccardo

AU - Liewald, David C.

AU - Fawns-Ritchie, Chloe

AU - Adams, Mark J.

AU - Howard, David

AU - Lewis, Cathryn

AU - Gale, Catharine R.

AU - McIntosh, Andrew M.

AU - Deary, Ian J.

PY - 2018/1/1

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N2 - Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3,4,5,6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. 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)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3,4,5,6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. 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.

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DO - 10.1038/s41588-017-0013-8

M3 - Article

SN - 1061-4036

VL - 50

SP - 6

EP - 11

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

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