Abstract

Neuroticism is a stable personality trait 1; twin studies report heritability between 30% and 50% 2, and SNP-based heritability is about 15% 3. Higher levels of neuroticism are associated with poorer mental and physical health 4,5, and the economic burden of neuroticism for societies is high 6. To date, genome-wide association (GWA) studies of neuroticism have identified up to 11 genetic loci 3,7. Here we report 116 significant independent genetic loci from a GWA of neuroticism in 329,821 UK Biobank participants, with replication available in a GWA meta-analysis of neuroticism in 122,867 individuals. Genetic signals for neuroticism were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = .82, SE=.03), major depressive disorder (rg = .69, SE=.07) and subjective wellbeing (rg = -.68, SE=.03) alongside other mental health traits. These discoveries significantly advance our understanding of neuroticism and its association with major depressive disorder.