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

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 Deary

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt); heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%. Increased neuroticism is associated with poorer mental and physical health, translating to high economic burden. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci. 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.
Original languageEnglish
Pages (from-to)6-11
Number of pages6
JournalNature Genetics
Early online date18 Dec 2017
Publication statusPublished - 31 Jan 2018


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