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Nat Genet. 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.

Author information

1
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK. michelle.luciano@ed.ac.uk.
2
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK.
3
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
4
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
5
Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
6
Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
7
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

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.

PMID:
29255261
PMCID:
PMC5985926
DOI:
10.1038/s41588-017-0013-8
[Indexed for MEDLINE]
Free PMC Article

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