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. 2018 Jan;50(1):6-11.
doi: 10.1038/s41588-017-0013-8. Epub 2017 Dec 18.

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

Michelle Luciano  1 , Saskia P Hagenaars  2   3 , Gail Davies  2 , W David Hill  2 , Toni-Kim Clarke  2   4 , Masoud Shirali  2   4 , Sarah E Harris  2   5 , Riccardo E Marioni  2   5   6 , David C Liewald  2 , Chloe Fawns-Ritchie  2 , Mark J Adams  2   4 , David M Howard  2   4 , Cathryn M Lewis  3 , Catharine R Gale  2   7 , Andrew M McIntosh  2   4   6 , Ian J Deary  2   6
Affiliations

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

Michelle Luciano et al. Nat Genet. 2018 Jan.

Erratum in

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% 3-6 . Increased neuroticism is associated with poorer mental and physical health 7,8 , translating to high economic burden 9 . Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci 3,4 . 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 (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.

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Conflict of interest statement

Author Disclosure

IJD was a participant in UK Biobank. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
GWA results for neuroticism in 329,821 UK Biobank individuals.
Figure 2
Figure 2
Regional association plot for suggestive/significant signals in UK Biobank on a) chromosome 8p (site of the inversion polymorphism), b) chromosome 11, and c) chromosome 22. The SNP association p-value is shown on the y-axis and the SNP position (with gene annotation) appears on the x-axis; for each SNP, the strength of LD with the lead SNP is colour coded based on its r2. Plots were produced in LocusZoom.
See this image and copyright information in PMC

References

    1. Matthews G, Deary IJ, Whiteman MC. Personality Traits. Cambridge University Press; 2009.
    1. Vukasovic T, Bratko D. Heritability of personality: A meta-analysis of behavior genetic studies. Psychological Bulletin. 2015;141 - PubMed
    1. Smith DJ, et al. Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci. Mol Psychiatry. 2016;21:749–57. - PMC - PubMed
    1. Okbay A, et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat Genet. 2016;48:624–33. - PMC - PubMed
    1. Power RA, Pluess M. Heritability estimates of the Big Five personality traits based on common genetic variants. Transl Psychiatry. 2015;5:e604. - PMC - PubMed

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