Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism
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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% 3-6 . 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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Overlap with neuroticism studies highlighted putative depression associations for DRD2, CELF4, and ELAVL2.
“Examining significant genes that overlap between the current meta-analysis of depression and the neuroticism studies of both Luciano, et al. 18 and Okbay, et al. 19 revealed putative associations with DRD2, CUGBP Elav-like family member 4 (CELF4) and ELAV like RNA binding protein 2 (ELAVL2).”
From Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions (2019) · cites this paper as [18]
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- Authors
- 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. J.
- Affiliations
- King's College London (GB)
- University of Edinburgh (GB)
- Western General Hospital (GB)
- ORCID
- Venue
- Nature Genetics
- Published
- 2017-12-18
- Volume
- 50
- Issue
- 1
- Pages
- 6-11
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5985926
- OpenAlex
- W2740637836
- Cited by
- 391
- References
- 61
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 34 · 2023: 44 · 2022: 44 · 2021: 46 · 2020: 82 · 2019: 51 · 2018: 34 · 2017: 4
- FWCI
- 30.96
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-01-29)
- Open access
- green
- doi.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- South London and Maudsley NHS Foundation Trust
- Wellcome Trust (104036/Z/14/Z)
- Scottish Government (CZD/16/6)
- National Institute for Health and Care Research (NF-SI-0508-10082, NF-SI-0513-10085)
- Scottish Funding Council (HR03006)
- Age UK (10279, MR/K026992/1)
- University of Southampton
- King's College London
- University of Edinburgh (MR/K026992/1, 10279)
- Centre for Cognitive Ageing and Cognitive Epidemiology (MR/K026992/1)
- Directorate for Biological Sciences
- Chief Scientist Office, Scottish Government Health and Social Care Directorate (CZD/16/6)
- Medical Research Council (MR/K026992/1, 10279, 104036/Z/14/Z, MR/S015132/1, MC_UU_12011/2, MC_UU_12011/1)
- Biotechnology and Biological Sciences Research Council (MR/K026992/1)
- Institute of Genetics
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Personality Traits and Psychology
- Keywords
- neuroticism, personality traits, genetic loci, major depressive disorder, depressive symptoms, subjective well-being, genetic correlation, neuronal differentiation, negative affectivity
- MeSH terms
- Neuroticism, Female, Humans, Male, Polymorphism, Single Nucleotide, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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