| Title: | Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism |
| Journal: | Nature Genetics |
| Published: | 18 Dec 2017 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29255261/ |
| DOI: | https://doi.org/10.1038/s41588-017-0013-8 |
| URL: | https://kclpure.kcl.ac.uk/ws/files/147268122/Association_analysis_in_over_329_000_LEWIS_Publishedonline18December2017_GREEN_AAM.pdf |
| Citations: | 300 (62 in last 2 years) as of 8 Aug 2024 |
Publication 3144
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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 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.</p>
6 Keywords
- Female
- Genome-Wide Association Study
- Humans
- Male
- Neuroticism
- Polymorphism, Single Nucleotide
16 Authors
- 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 J. Deary
1 Application
| Application ID | Title |
|---|---|
| 10279 | The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation |
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