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. and Deary, I.J. (2018) Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism. Nature Genetics, 50 (1), 6-11. (doi:10.1038/s41588-017-0013-8).
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.
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